ITIC: A Long-Term, Placebo-Controlled X-Ray Study Investigating the Safety and Efficacy of SD-6010 in Subjects With Osteoarthritis of the Knee
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00565812
Collaborator
(none)
1,457
183
3
48
8
0.2
Study Details
Study Description
Brief Summary
The objective of this 2-year study is to evaluate the safety, tolerability and disease modifying efficacy of SD 6010, an inhibitor of inducible nitric oxide synthase (iNOS), in overweight and obese subjects with knee osteoarthritis. The efficacy of SD-6010 will be evaluated by radiography using joint space narrowing in the medial tibiofemoral compartment of the study knee as the primary endpoint.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1457 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Long-Term, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Radiographic Study To Investigate The Safety And Efficacy Of Orally Administered SD-6010 In Subjects With Symptomatic Osteoarthritis Of The Knee
Study Start Date
:
Nov 1, 2007
Actual Primary Completion Date
:
Oct 1, 2011
Actual Study Completion Date
:
Nov 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 200 mg High dose active comparator |
Drug: SD-6010
200 mg tablets once a day for 2 years
|
| Active Comparator: 50 mg Low dose active comparator |
Drug: SD-6010
50 mg tablets once a day for 2 years
|
| Placebo Comparator: Placebo Placebo comparator to be used for control purposes |
Drug: Placebo
Placebo tablets once a day for 2 years
|
Outcome Measures
Primary Outcome Measures
- Rate of Progression of Joint Space Narrowing [Baseline up to Month 24]
Rate of progression of joint space narrowing (JSN) was defined as narrowing in joint space width (JSW) over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in millimeter per year (mm/year) over a 2 year period was used to assess the rate of progression of JSN. Negative values indicating a worsening of osteoarthritis.
- Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Less Than or Equal to (<=) 2 [Baseline up to Month 24]
Rate of progression of JSN was defined as narrowing in joint space width over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in mm/year over a 2 year period was used to assess the rate of progression of JSN. KLG system was a method of classifying the severity of knee OA using five grades (0 [no severity] to 4 [maximum severity], higher grade indicating worse knee function). Negative values of slope indicating a worsening of osteoarthritis.
- Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Equal to (=) 3 [Baseline up to Month 24]
Rate of progression of JSN was defined as narrowing in joint space width over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in mm/year over a 2 year period was used to assess the rate of progression of JSN. KLG system was a method of classifying the severity of knee OA using five grades (0 [no severity] to 4 [maximum severity], higher grade indicating worse knee function). Negative values of slope indicating a worsening of osteoarthritis.
Secondary Outcome Measures
- Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index (WOMAC) Composite Index Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The WOMAC was a self-administered, disease-specific instrument which probed clinically important, participant relevant symptoms in the areas of pain, stiffness, and physical function in participants with OA of the knee. The WOMAC composite index was the sum of 24 individual questions regarding subscales of pain, stiffness and physical function (for each item score range: 0 [minimum] to 4 [maximum], higher score indicating worse knee condition). Total score was sum of the 3 subscale scores, giving a possible overall score range of 0 (minimum) to 96 (maximum). Higher score indicating the worse level of pain, stiffness and physical function.
- Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Subscale Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The WOMAC pain subscale was comprised of 5 questions regarding the amount of pain experienced due to OA in the study knee. The WOMAC pain subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse pain. An overall subscale score range of 0 (minimum) to 20 (maximum), with higher scores indicating more pain.
- Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Stiffness Subscale Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
Stiffness was defined as a sensation of decreased ease in which the participant moved the knee with OA. The WOMAC stiffness subscale was comprised of 2 questions regarding the degree of stiffness experienced in the study knee. The WOMAC stiffness subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse stiffness. An overall score range of 0 (minimum) to 8 (maximum), with higher scores indicating more stiffness.
- Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Physical Function Subscale Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The WOMAC physical function subscale referred to the participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was comprised of 17 questions regarding the degree of difficulty experienced due to OA in the study knee. The WOMAC physical function subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse physical function. An overall score range of 0 (minimum) to 68 (maximum), with higher scores indicating worse physical function.
- Change From Baseline in Patient Assessment of Arthritic Pain Visual Analog Scale (VAS) Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
Pain VAS was a self-administered instrument, a 100 millimeter (mm) line marked by participant. Intensity of pain range (over past week): 0 (mm) =no pain to 100 (mm) =worst possible pain. Higher score indicating severe pain.
- Change From Baseline in Patient Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using the scale ranging from 1 (minimum) to 5 (maximum), where 1 =very good, 2 =good, 3 =fair, 4 =poor and 5 =very poor. Higher scores indicating worse condition.
- Change From Baseline in Physician's Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
Physician assessed the overall impact of arthritis on the participant's daily life. Participant's condition was rated by the physician using the scale ranging from 1 (minimum) to 5 (maximum), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicating worse condition.
- Change From Baseline in Pain After a 50-foot Walk Using Pain Visual Analog Scale Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The pain VAS following a 50 foot walk was a single-item, self-administered instrument. Participants were asked to assess the pain due to OA in their study knee after a 50-foot walk. Participants responded on a VAS scale ranging from 0 (no pain) to 100 (severe pain). Higher scores indicating more pain.
- Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Total Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The OA pain and assessment tool-knee joint is also known as the intermittent and constant osteoarthritis pain (ICOAP) scale. The OA pain assessment tool-knee joint was an 11-item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. The total score was calculated by adding the 11 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse health.
- Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Constant Pain Subscale Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The OA pain assessment tool-knee joint constant pain subscale was a 5 item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Overall subscale score was calculated by adding the 5 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse constant pain.
- Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Intermittent Pain Subscale Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The OA pain assessment tool-knee joint intermittent pain subscale score a 6 item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Overall subscale score was calculated by adding the 6 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse intermittent pain.
- Change From Baseline in Osteoarthritis Research Society International (OARSI) Knee Function Survey Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The OARSI knee function survey was an 11-item scale with each item scored 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. The total score was the sum of the 11 items and ranged from 0 (minimum) to 44 (maximum), where higher scores indicating worse health condition.
- Change From Baseline in Knee Injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS) Score at Month 3, 6, 12, 18 and 24 [Baseline, Month 3, 6, 12, 18, 24]
The KOOS-PS was used to rate participant's opinions about the difficulties they experienced with activity due to problems with their knee. It was a 7-item scale, each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Total score was calculated by adding the responses to 7 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse health condition.
- Change From Baseline in Short Form-36 (SF-36) Physical Functioning Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 16.18 (minimum) to 57.11 (maximum), with higher scores indicating better physical functioning.
- Change From Baseline in Short Form-36 Role - Physical Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 18.45 (minimum) to 56.62 (maximum), with higher scores indicating better role-physical.
- Change From Baseline in Short Form-36 Bodily Pain Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 19.23 (minimum) to 60.88 (maximum), with higher scores indicating lower bodily pain.
- Change From Baseline in Short Form-36 General Health Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 16.75 (minimum) to 63.72 (maximum), with higher scores indicating better general health.
- Change From Baseline in Short Form-36 Vitality Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 22.02 (minimum) to 69.92 (maximum), with higher scores indicating better vitality.
- Change From Baseline in Short Form-36 Social Functioning Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 13.38 (minimum) to 56.40 (maximum), with higher scores indicating better social functioning.
- Change From Baseline in Short Form-36 Role-Emotional Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 10.25 (minimum) to 55.68 (maximum), with higher scores indicating better role-emotional.
- Change From Baseline in Short Form-36 Mental Health Domain Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 8.02 (minimum) to 63.43 (maximum), with higher scores indicating better mental health.
- Change From Baseline in Short Form-36 Physical Health Component Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 22.88 (minimum) to 58.69 (maximum), with higher scores indicating better physical health.
- Change From Baseline in Short Form-36 Mental Health Component Score at Month 12 and 24 [Baseline, Month 12, 24]
The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 11.11 (minimum) to 61.67 (maximum), with higher scores indicating better mental health.
- Number of Participants With EuroQoL-5D (EQ-5D) Mobility Domain Score [Baseline, Month 12, 24]
EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D mobility domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problem), 2 =moderate health (some problems) and 3 =worst health (confined to bed). Higher scores indicating worse health condition. Participants with EQ-5D mobility domain score were reported in this measure.
- Number of Participants With EuroQoL-5D Self-Care Domain Score [Baseline, Month 12, 24]
EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D self-care domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problems with self-care), 2 =moderate health (some problems) and 3 =worst health (unable to wash or dress). Higher scores indicating worse health condition. Participants with EQ-5D self-care domain score were reported in this measure.
- Number of Participants With EuroQoL-5D Usual Activity Domain Score [Baseline, Month 12, 24]
EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D usual activity domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problems), 2 =moderate health (some problems) and 3 =worst health state (unable to perform usual activities). Higher scores indicating worse health condition. Participants with EQ-5D usual activity domain score were reported in this measure.
- Number of Participants With EuroQo-5D Pain and Discomfort Domain Score [Baseline, Month 12, 24]
EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D pain and discomfort domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no pain and discomfort), 2 =moderate health (moderate pain and discomfort) and 3 =worst health state (extreme pain and discomfort). Higher scores indicated worse health condition. Participants with EQ-5D pain and discomfort domain score were reported in this measure.
- Number of Participants With EuroQoL-5D Anxiety and Depression Domain Score [Baseline, Month 12, 24]
EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. EQ-5D anxiety and depression domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (not anxious, depressed), 2 =moderate health (moderately anxious, depressed) and 3 =worst health (extremely anxious, depressed). Higher scores indicating worse health condition. Participants with EQ-5D anxiety and depression domain score were reported in this measure.
- EuroQoL-5D Visual Analog Scale Score [Baseline, Month 12, 24]
The EQ-5D VAS score was a participant rated questionnaire to assess health-related quality of life in terms of a single index value. It was a visual analogue scale that ranged from 0 (minimum) to 100 (maximum), with higher scores indicating a better health condition.
- Number of Participants With Increase in Total Analgesic Medication Use [Month 12, 24]
Increase in total analgesic medication use for OA in the study knee was a comparison back to baseline of an increased and sustained use of standard background and/or rescue medication for more than 28 days as measured at the Month 12 and 24 visits. Only medications for OA knee pain were considered.
- Number of Participants With Decrease in Total Analgesic Medication Use [Month 12, 24]
Decrease in total analgesic medication use for OA in the study knee was a comparison back to baseline of a decreased and irregular use of standard background and/or rescue medication for more than 28 days as measured at the Month 12 and 24 visits. Only medications for OA knee pain were considered.
- Patient Global Impression of Change Score [Month 24]
Patient global impression of change was a participant-rated instrument that measured change in participant's overall status on a 7-point scale ranging from: 1 =very much improved, 2 =much improved, 3 =minimally improved, 4 =no change, 5 =minimally worse, 6 =much worse and 7 =very much worse. Higher scores indicating worse condition.
- Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index [Month 24]
The OMERACT-OARSI responder index was used to determine whether participants may be considered responders to treatment. An OMERACT-OARSI responder was a participant who had a better response on the WOMAC pain subscale score, a better response on the WOMAC physical function subscale score or improvement on at least two of the three domains: WOMAC pain subscale score (overall score range of 0 [minimum] to 20 [maximum], higher scores indicating more pain), WOMAC physical function subscale score (overall score range of 0 [minimum] to 68 [maximum], higher scores indicating worse physical function) and patient global assessment of arthritic condition score (overall score range of 1 [minimum] to 5 [maximum], higher scores indicating worse condition). Number of participants who were OMERACT-OARSI responder were reported in this measure.
- Number of Participants With Joint Space Narrowing Progression [Month 24]
JSN progressor was defined as a participant with a decrease in joint space width that was greater in magnitude than the smallest detectable difference (0.199 mm).
- Number of Participants Applicable for Virtual Joint Replacement [Month 24]
A virtual joint replacement candidate was defined as a participant whose last two WOMAC pain subscale scores (overall score range of 0 [minimum] to 20 [maximum], higher scores indicating more pain) were at least 8, last two WOMAC physical function subscale scores (overall score range of 0 [minimum] to 68 [maximum], higher scores indicating worse physical function) were at least 28 and was a joint space narrowing progressor (a participant with a decrease in JSW that was greater in magnitude than the smallest detectable difference =0.199 mm).
Other Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to 7-10 days after last dose of study drug (Week 111)]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 7-10 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Adverse events included both serious and non-serious adverse events.
- Number of Participants With Electrocardiogram (ECG) Abnormalities [Baseline, Month 3, 6, 12, 18, 24]
Atrial (enlargement, fibrillation, premature beat), axis deviation, atrioventricular (accelerated conduction, first/second degree block), left anterior and posterior hemiblock, left atrial hypertrophy, left and right (complete/incomplete bundle branch block, ventricular hypertrophy), QRS (high/low voltage, nonspecific, prolongation greater than [>]140 milliseconds [msec]), junctional/paced rhythm, intraventricular conduction delay (>120 msec), early repolarization, ventricular premature contraction and beat, prolonged QTC, sinus (arrhythmia, bradycardia/tachycardia), supraventricular extra systole and premature beat, short PR syndrome. Abnormal Q-wave (>=30 msec), P-wave left/right atrial abnormality, T-wave flattened/inverted abnormality, U-wave abnormality, ST-T indeterminate abnormality, ST-T nonspecific changes, ST-T changes compatible with ischemia and pericarditis. ECG findings were judged by investigators for qualitative evaluation of abnormalities.
- Number of Participants With Laboratory Test Abnormalities [Baseline up to Week 111]
Criteria for laboratory abnormalities: Hemoglobin (Hgb), hematocrit (hct), red blood cell(RBC) count: less than(<)0.8*lower limit of normal(LLN), platelet: <0.5*LLN or greater than (>)1.75*upper limit of normal (ULN), white blood cell (WBC): <0.6*LLN or >1.5*ULN, lymphocyte, neutrophil:<0.8*LLN or >1.2*ULN, basophil, eosinophil, monocyte:>1.2*ULN; total bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, gammaglutamyl transferase, alkaline phosphatase:> 3.0*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN; blood urea nitrogen, creatinine:>1.3*ULN, uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, magnesium, bicarbonate: <0.9*LLN or >1.1*ULN, phosphate <0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN, lipase >1.5*ULN; urine (specific gravity <1.003 or >1.030, pH <4.5 or >8, glucose, ketones, protein, blood/Hgb greater than or equal to [>=]1); pancreatic amylase >1.5*ULN.
- Change From Baseline in Systolic Blood Pressure (SBP) at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96 [Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96]
Blood pressure (BP) was measured by sphygmomanometer while participant was in supine position. Conditions were kept constant from visit to visit including observer, participant's same arm, cuff size, supine position, location, temperature, noise level. The same size BP cuff which was properly sized and calibrated, was used to measure BP each time.
- Change From Baseline in Diastolic Blood Pressure (DBP) at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96 [Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96]
BP was measured by sphygmomanometer while participant was in supine position. Conditions were kept constant from visit to visit including observer, participant's same arm, cuff size, supine position, location, temperature, noise level. The same size BP cuff which was properly sized and calibrated, was used to measure BP each time.
- Change From Baseline in Heart Rate at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96 [Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96]
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Subjects aged >= 40 years with a BMI >= 25 and <= 40 kg/m2
-
In the past, has been diagnosed with knee OA
-
Radiographic evidence of OA in the study knee
Exclusion Criteria:
-
A diagnosis of any other rheumatic disease
-
Current conditions in the study knee that would confound efficacy
-
Selected, traditional clinical safety and laboratory parameters
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Brookwood Internists, P.C. | Birmingham | Alabama | United States | 35209 |
| 2 | Greystone Medical Center | Birmingham | Alabama | United States | 35242 |
| 3 | Pivotal Research Centers | Peoria | Arizona | United States | 85381 |
| 4 | Arizona Research Center | Phoenix | Arizona | United States | 85023 |
| 5 | Pivotal Research Centers | Phoenix | Arizona | United States | 85027 |
| 6 | University of Arizona | Tucson | Arizona | United States | 85724 |
| 7 | Martin Bowen Hefley Orthopedics | Little Rock | Arkansas | United States | 72205 |
| 8 | Teton Research, LLC | Little Rock | Arkansas | United States | 72205 |
| 9 | Med Center | Carmichael | California | United States | 95608 |
| 10 | College Hospital Costa Mesa | Costa Mesa | California | United States | 92627 |
| 11 | NeuroNetwork Trials | Costa Mesa | California | United States | 92627 |
| 12 | Med Investigations, Inc. | Fair Oaks | California | United States | 95628 |
| 13 | Sierra Clinical Research | Roseville | California | United States | 95661 |
| 14 | University of California Davis Health System | Sacramento | California | United States | 95817 |
| 15 | University of California Davis | Sacramento | California | United States | 95817 |
| 16 | Scripps Clinic-Clinical Research | San Diego | California | United States | 92128 |
| 17 | Plaza Medical Imaging | Santa Ana | California | United States | 92704 |
| 18 | Denver Internal Medicine Group | Denver | Colorado | United States | 80209 |
| 19 | Mountain View Clinical Research, Inc. | Denver | Colorado | United States | 80209 |
| 20 | New West Physicians Clinical Research | Golden | Colorado | United States | 80401 |
| 21 | Advanced Radiology Consultants | Fairfield | Connecticut | United States | 06824 |
| 22 | Advanced Radiology Consultants | Stamford | Connecticut | United States | 06902 |
| 23 | Stamford Therapeutics Consortium | Stamford | Connecticut | United States | 06905 |
| 24 | New England Research Associates, LLC | Trumbull | Connecticut | United States | 06611 |
| 25 | Southeastern Arthritis Center | Gainesville | Florida | United States | 32607 |
| 26 | Southeastern Imaging & Diagnostics | Gainesville | Florida | United States | 32607 |
| 27 | Southeastern Integrated Medical, PL, d/b/a Florida Medical Research Institute | Gainesville | Florida | United States | 32607 |
| 28 | Jacksonville Center for Clincal Research | Jacksonville | Florida | United States | 32216 |
| 29 | Memorial Hospital Jacksonville | Jacksonville | Florida | United States | 32216 |
| 30 | Gold Coast Research, LLC | Plantation | Florida | United States | 33317 |
| 31 | Marin E. Hale, M.D., P.A. | Plantation | Florida | United States | 33317 |
| 32 | Sabiha Khan, M.D. | Plantation | Florida | United States | 33324 |
| 33 | Kanner, Mendelson, Shteinman, LLC | West Palm Beach | Florida | United States | 33407 |
| 34 | Radiant Research | West Palm Beach | Florida | United States | 33407 |
| 35 | Rheumatology and Endocrinology Specialists of the Palm Beaches, P.A. | West Palm Beach | Florida | United States | 33407 |
| 36 | North Georgia Clinical Research | Marietta | Georgia | United States | 30060 |
| 37 | North Georgia Clinical Research | Woodstock | Georgia | United States | 30189 |
| 38 | East-West Medical Research Institute | Honolulu | Hawaii | United States | 96814 |
| 39 | Preventive Medicine | Chicago | Illinois | United States | 60611 |
| 40 | Rehabilitation Institue of Chicago | Chicago | Illinois | United States | 60611 |
| 41 | NorthShore University HealthSystem | Evanston | Illinois | United States | 60201 |
| 42 | NorthShore University HealthSystem | Glenview | Illinois | United States | 60025 |
| 43 | Clinical Investigation Specialists, Inc. | Gurnee | Illinois | United States | 60031 |
| 44 | Illinois Bone and Joint Institute, LLC | Morton Grove | Illinois | United States | 60053 |
| 45 | The Arthritis Center | Springfield | Illinois | United States | 62704 |
| 46 | NorthShore University HealthSystem | Vernon Hills | Illinois | United States | 60061 |
| 47 | Ronald Keith Stegemoller, American Health Network | Avon | Indiana | United States | 46123 |
| 48 | Floyd Memorial Hospital | New Albany | Indiana | United States | 47150 |
| 49 | Heartland Research Associates, LLC | Wichita | Kansas | United States | 67205 |
| 50 | Family Medicine East, Chartered/Radiology | Wichita | Kansas | United States | 67207 |
| 51 | Heartland Research Associates, LLC | Wichita | Kansas | United States | 67207 |
| 52 | Office of Manoj Kohli, M.D. | Lexington | Kentucky | United States | 40517 |
| 53 | L-MARC Research Center | Louisville | Kentucky | United States | 40213 |
| 54 | Commonwealth Biomedical Research, LLC | Madisonville | Kentucky | United States | 42431 |
| 55 | TFD Research, LLC | Shreveport | Louisiana | United States | 71115 |
| 56 | Rheumatology Associates | Portland | Maine | United States | 04102 |
| 57 | The Center for Rheumatology and Bone Research | Rockville | Maryland | United States | 20850 |
| 58 | The Center for Rheumatology and Bone Research | Wheaton | Maryland | United States | 20902 |
| 59 | Miray Medical Center | Brockton | Massachusetts | United States | 02301 |
| 60 | Phase III Clinical Research | Fall River | Massachusetts | United States | 02720 |
| 61 | Fall River Clinical Research | Fall River | Massachusetts | United States | 02721 |
| 62 | HCI Metromedic Walk-In | New Bedford | Massachusetts | United States | 02740 |
| 63 | MedVadis Research Corporation | Wellesley Hills | Massachusetts | United States | 02481-2106 |
| 64 | Fallon Clinic, Inc. (Drug Shipment) | Worcester | Massachusetts | United States | 01605 |
| 65 | Fallon Clinic, Inc. | Worcester | Massachusetts | United States | 01605 |
| 66 | Cadillac Clinical Research, LLC, located at Great Lakes Family Care | Cadillac | Michigan | United States | 49601 |
| 67 | Arthritis and Osteoporosis Treatment and Research Center | Flowood | Mississippi | United States | 39232 |
| 68 | Planters Clinic | Port Gibson | Mississippi | United States | 39150 |
| 69 | North Mississippi Medical Center, Inc. | Tupelo | Mississippi | United States | 38801 |
| 70 | Mercy Medical Group/Woodlake Research | Clarkson Valley | Missouri | United States | 63011 |
| 71 | Dynamic Clinical Research, Inc. | Kansas City | Missouri | United States | 64114 |
| 72 | Joan Prouty Moore, MD | Kansas City | Missouri | United States | 64114 |
| 73 | Orthopaedic and Occupational Medicine | Kansas City | Missouri | United States | 64114 |
| 74 | The Center for Pharmaceutical Research, P.C. | Kansas City | Missouri | United States | 64114 |
| 75 | Affiliated Clinical Research, Inc. | Las Vegas | Nevada | United States | 89106 |
| 76 | Office of Michael Mall, M.D. | Las Vegas | Nevada | United States | 89109 |
| 77 | Nevada Imaging Centers | Las Vegas | Nevada | United States | 89117 |
| 78 | Nevada Imaging Centers | Las Vegas | Nevada | United States | 89118 |
| 79 | Office of Danka Michaels, MD | Las Vegas | Nevada | United States | 89128 |
| 80 | Office of Stephen H. Miller, MD | Las Vegas | Nevada | United States | 89144 |
| 81 | Regional Clinical Research, Inc. | Endwell | New York | United States | 13760 |
| 82 | NYU Hospital for Joint Diseases | New York | New York | United States | 10003 |
| 83 | VirtualScopics, Inc. | Rochester | New York | United States | 14625 |
| 84 | Crouse Medical Practice, PLLC d/b/a Internist Associates of Central New York | Syracuse | New York | United States | 13210 |
| 85 | Kernodle Clinic Inc. | Burlington | North Carolina | United States | 27215 |
| 86 | Southeastern Radiology | Greensboro | North Carolina | United States | 27407 |
| 87 | PharmQuest | Greensboro | North Carolina | United States | 27408 |
| 88 | Research Institute of the Carolinas, PLLC | Mooresville | North Carolina | United States | 28117 |
| 89 | PMG Research of Salisbury | Salisbury | North Carolina | United States | 28144 |
| 90 | Piedmont Healthcare/Research | Statesville | North Carolina | United States | 28625 |
| 91 | Carolina Arthritis Associates, PA | Wilmington | North Carolina | United States | 28401 |
| 92 | PMG Research of Wilmington, LLC | Wilmington | North Carolina | United States | 28401 |
| 93 | Internal Medicine Associates | Fargo | North Dakota | United States | 58103 |
| 94 | Lillestol Research, LLC | Fargo | North Dakota | United States | 58103 |
| 95 | Advantage Diagnostics | Beachwood | Ohio | United States | 44122 |
| 96 | Rapid Medical Research, Inc. | Cleveland | Ohio | United States | 44122 |
| 97 | Columbus Clinical Research, Inc. | Columbus | Ohio | United States | 43213 |
| 98 | Optimed Research, LLC | Columbus | Ohio | United States | 43235 |
| 99 | Lake Health Lyndhurst Clinic | Lyndhurst | Ohio | United States | 44124 |
| 100 | East Penn Rheumatology Associates, PC | Bethlehem | Pennsylvania | United States | 18015 |
| 101 | Altoona Center for Clinical Research | Duncansville | Pennsylvania | United States | 16635 |
| 102 | BioImaging Technologies, Inc. | Newtown | Pennsylvania | United States | 18940 |
| 103 | Memorial Hospital of Rhode Island | Pawtucket | Rhode Island | United States | 02860 |
| 104 | Rheumatology Associates | Charleston | South Carolina | United States | 29407 |
| 105 | Radiant Research, Inc. | Greer | South Carolina | United States | 29651 |
| 106 | Parkway Medical Group | Fayetteville | Tennessee | United States | 37334 |
| 107 | Holston Medical Group | Kingsport | Tennessee | United States | 37660 |
| 108 | D. Matthew Sellers MD PC | Knoxville | Tennessee | United States | 37920 |
| 109 | Southwind Medical Specialists | Memphis | Tennessee | United States | 38125 |
| 110 | Baylor Research Institute | Dallas | Texas | United States | 75231 |
| 111 | Metroplex Clinical Research Center | Dallas | Texas | United States | 75231 |
| 112 | Radiant Research San Antonio Northeast | San Antonio | Texas | United States | 78217 |
| 113 | South Texas Radiology Imaging Center | San Antonio | Texas | United States | 78217 |
| 114 | Oakwell Clinical Research, LLC | San Antonio | Texas | United States | 78218 |
| 115 | Pivotal Research Centers | Midvale | Utah | United States | 84047 |
| 116 | National Clinical Research - Norfolk, Inc. | Norfolk | Virginia | United States | 23502 |
| 117 | National Clinical Research, Incorporated | Richmond | Virginia | United States | 23294 |
| 118 | Advanced Pain Management | Virginia Beach | Virginia | United States | 23454 |
| 119 | Tacoma Center for Arthritis Research, PS | Tacoma | Washington | United States | 98405 |
| 120 | Clinical Investigation Specialists, Inc. | Kenosha | Wisconsin | United States | 53142 |
| 121 | OMI - Organización Médica de Investigación | Buenos Aires | Argentina | C1013AAR | |
| 122 | Saint Dennis Medical Group S.A. | Buenos Aires | Argentina | C1034ACO | |
| 123 | Investigaciones Reumatológicas y Osteológicas S.R.L. | Buenos Aires | Argentina | C1114AAH | |
| 124 | Instituto Médico Especializado (IME) | Buenos Aires | Argentina | C1405BCH | |
| 125 | IMAI Research | Buenos Aires | Argentina | C1425AWC | |
| 126 | Menzies Research Institute | Hobart | Tasmania | Australia | 7000 |
| 127 | Cliniques Universitaires St Luc | Bruxelles | Belgium | 1200 | |
| 128 | Universitair Ziekenhuis Gasthuisberg / Rheumatology | Leuven | Belgium | 3000 | |
| 129 | Rheumatology Research Associates Ltd. | Edmonton | Alberta | Canada | T5M 0H4 |
| 130 | Nexus Clinic Research | St. John's | Newfoundland and Labrador | Canada | A1A 5E8 |
| 131 | The Arthritis Program Research Group Inc. | Newmarket | Ontario | Canada | L3Y 3R7 |
| 132 | Centre de Rhumatologie St-Louis | Sainte-Foy | Quebec | Canada | G1W 4R4 |
| 133 | Revmacentrum MUDr. Mostera, s.r.o. | Brno - Zidenice | Czech Republic | 615 00 | |
| 134 | Fakultni nemocnice u sv. Anny v Brne | Brno | Czech Republic | 656 91 | |
| 135 | MEDIPONT Plus, s.r.o. | Ceske Budejovice | Czech Republic | 370 01 | |
| 136 | MEDIPONT, s.r.o. | Ceske Budejovice | Czech Republic | 370 01 | |
| 137 | ARTMEDI UPD s r.o. | Hostivice | Czech Republic | 253 01 | |
| 138 | DC Mediscan | Praha 11 - Chodov | Czech Republic | 148 00 | |
| 139 | MediCentrum Praha, a.s. | Praha 11 - Chodov | Czech Republic | 148 00 | |
| 140 | Nemocnice Na Frantisku s poliklinikou | Praha 1 | Czech Republic | 11000 | |
| 141 | Revmatologicky ustav | Praha 2 | Czech Republic | 128 50 | |
| 142 | Centrum pro zdravotnicke zabezpeceni sportovni reprezentace | Praha 6 | Czech Republic | 162 00 | |
| 143 | Ustredni vojenska nemocnice Praha | Praha 6 | Czech Republic | 162 00 | |
| 144 | MSI - Muskuloskeletalni institut | Praha 6 | Czech Republic | 169 00 | |
| 145 | Nemocnice Atlas, a.s. | Zlin | Czech Republic | 760 01 | |
| 146 | PV-Medical s.r.o. | Zlin | Czech Republic | 760 01 | |
| 147 | Praxis fuer Orthopaedie, Chirotherapie und Akupunktur | Bad Hersfeld | Germany | 36251 | |
| 148 | Praxis fuer Orthopaedie | Berlin | Germany | 12247 | |
| 149 | Klinische Forschung Berlin-Buch | Berlin | Germany | 13125 | |
| 150 | Praxis Dr. Thomas Jung | Deggingen | Germany | 73326 | |
| 151 | Klinische Forschung Schwerin | Schwerin | Germany | 19055 | |
| 152 | Orszagos Gerincgyogyaszati Kozpont | Budapest | Hungary | 1126 | |
| 153 | Synexus Magyarorszag Kft. | Budapest | Hungary | H-1036 | |
| 154 | Heves Megyei Onkormanyzat Markhot Ferenc Korhaz | Eger | Hungary | 3300 | |
| 155 | Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz, Reumatologia | Gyula | Hungary | 5700 | |
| 156 | Selye Janos Korhaz, Reumatologiai Szakrendelo | Komarom | Hungary | 2900 | |
| 157 | MAV Korhaz es Rendelointezet | Szolnok | Hungary | H-5000 | |
| 158 | Veszprem Megyei Onkormanyzat Csolnoky Ferenc Korhaz-Rendelointezet | Veszprem | Hungary | H-8200 | |
| 159 | Azienda Sanitaria Genovese, Ospedale La Colletta, Dipartimento Apparato Locomotore | Arenzano | Italy | 16011 | |
| 160 | Presidio Ospedaliero Augusto Murri, Reparto di Reumatologia | Jesi (Ancona) | Italy | 60035 | |
| 161 | Ospedale Luigi Sacco, Azienda Ospedaliera Polo Universitario Unita' Operativa di Reumatologia | Milano | Italy | 20157 | |
| 162 | Centro Empresarial - Altavista Polo 4 | Santiago de Surco | Lima | Peru | Lima 33 |
| 163 | Instituto de Ginecologia y Reproducción & Cirugia Minimamente Invasiva | Santiago de Surco | Lima | Peru | Lima 33 |
| 164 | Hospital Nacional "Alberto Sabogal Sologuren" - Essalud | Callao | Peru | Callao-02 | |
| 165 | ClÃnica San Felipe | Lima | Peru | L-11 | |
| 166 | Hospital Nacional "Edgardo Rebagliati Martins" - Essalud | Lima | Peru | L-11 | |
| 167 | Instituto Peruano del Hueso y la Articulación SAC. | Lima | Peru | L-27 | |
| 168 | Hospital Maria Auxiliadora | Lima | Peru | L-29 | |
| 169 | Centro Medico Corpac | Lima | Peru | Lima-27 | |
| 170 | NSZOZ "MEDICUS II" S.C. Irena Klimczak, Malgorzata Klimczak, Jerzy Klimczak | Cieszyn | Poland | 43-400 | |
| 171 | "SYNEXUS SCM" Sp. z o.o. | Wroclaw | Poland | 50-088 | |
| 172 | Katedra i Klinika Ortopedii i Traumatologii Narzadu Ruchu | Wroclaw | Poland | 50-556 | |
| 173 | Russian State Medical University, Moscow Faculty, City Clinical Hospital #4 | Moscow | Russian Federation | 115093 | |
| 174 | Institute of Rheumatology | Moscow | Russian Federation | 115522 | |
| 175 | City Alexandrovskaya Hospital | St. Petersburg | Russian Federation | 193312 | |
| 176 | L.G. Sokolov Clinical Hospital #122 of Federal Medical-Biology Agency of Russia, Central Polyclinic | St. Petersburg | Russian Federation | 194291 | |
| 177 | Research Institute of Traumatology and Orthopedy Named After R. R. Vredena | St. Petersburg | Russian Federation | 195427 | |
| 178 | V. Interna klinika FN a LF UK | Bratislava | Slovakia | 826 06 | |
| 179 | Ivan Ujvari | Bratislava | Slovakia | ||
| 180 | Narodny ustav reumatickych chorob | Piestany | Slovakia | 921 12 | |
| 181 | Hospital Ntra. Sra. de La Esperanza | Santiago de Compostela | A Coruña | Spain | 15705 |
| 182 | Hospital General Universitario de Guadalajara | Guadalajara | Spain | 19002 | |
| 183 | Hospital Nuestra Señora de Valme | Sevilla | Spain | 41014 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00565812
Other Study ID Numbers:
- A6171016
- 2007-001457-26
- ITIC
First Posted:
Nov 30, 2007
Last Update Posted:
Dec 30, 2016
Last Verified:
Nov 1, 2016
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 5077 participants were screened in the study, out of which only 1457 participants were randomized. |
| Arm/Group Title | SD-6010 50 Milligram (mg) | SD-6010 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Period Title: Overall Study | |||
| STARTED | 485 | 486 | 486 |
| COMPLETED | 341 | 351 | 356 |
| NOT COMPLETED | 144 | 135 | 130 |
Baseline Characteristics
| Arm/Group Title | SD-6010 50 Milligram (mg) | SD-6010 200 mg | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. | Total of all reporting groups |
| Overall Participants | 485 | 486 | 486 | 1457 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
61.0
(8.7)
|
60.8
(8.6)
|
61.3
(9.1)
|
61.0
(8.8)
|
| Gender (Count of Participants) | ||||
| Female |
383
79%
|
367
75.5%
|
364
74.9%
|
1114
76.5%
|
| Male |
102
21%
|
119
24.5%
|
122
25.1%
|
343
23.5%
|
Outcome Measures
| Title | Rate of Progression of Joint Space Narrowing |
|---|---|
| Description | Rate of progression of joint space narrowing (JSN) was defined as narrowing in joint space width (JSW) over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in millimeter per year (mm/year) over a 2 year period was used to assess the rate of progression of JSN. Negative values indicating a worsening of osteoarthritis. |
| Time Frame | Baseline up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'number of participants analyzed' (N) signifies participants evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 422 | 428 | 434 |
| Mean (Standard Deviation) [mm/year] |
-0.101
(0.346)
|
-0.125
(0.298)
|
-0.109
(0.261)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Slopes, 95 percent confidence interval (CI), P-values: Random coefficients mixed-effects model for repeated measures (MMRM) with random intercept and slope for each participant,fixed effects for treatment group,time (years),treatment group*time interaction,(collapsed)Kellgren and Lawrence Grades (KLG), KLG*time interaction,geographic region,gender,age,body mass index with unstructured covariance matrix for random effects. Statistical hypothesis used Hochberg procedure with 2-sided alpha =0.0499. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.508770 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Slopes |
| Estimated Value | 0.012 | |
| Confidence Interval |
(2-Sided) 95% -0.023 to 0.046 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.018 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Slopes, 95 percent CI, P-values: MMRM with random intercept and slope for each participant, fixed effects for treatment group, time (years), treatment group*time interaction, (collapsed) KLG, KLG*time interaction, geographic region, gender, age, body mass index with unstructured covariance matrix for random effects. Statistical hypothesis used Hochberg procedure with 2-sided alpha=0.0499. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.754074 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Slopes |
| Estimated Value | 0.005 | |
| Confidence Interval |
(2-Sided) 95% -0.029 to 0.040 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.017 |
|
| Estimation Comments | ||
| Title | Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Less Than or Equal to (<=) 2 |
|---|---|
| Description | Rate of progression of JSN was defined as narrowing in joint space width over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in mm/year over a 2 year period was used to assess the rate of progression of JSN. KLG system was a method of classifying the severity of knee OA using five grades (0 [no severity] to 4 [maximum severity], higher grade indicating worse knee function). Negative values of slope indicating a worsening of osteoarthritis. |
| Time Frame | Baseline up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'N' signifies participants with KLG <=2 and evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 184 | 172 | 194 |
| Mean (Standard Deviation) [mm/year] |
-0.061
(0.335)
|
-0.069
(0.254)
|
-0.075
(0.221)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Slopes, 95 percent CI and P-values were obtained from a random coefficients MMRM with random intercept and slope for each participant, and fixed effects for treatment group, time (years), a treatment group*time (years) interaction, geographic region, gender, age, and body mass index with an unstructured covariance matrix for the random effects. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.312 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in slopes |
| Estimated Value | 0.023 | |
| Confidence Interval |
(2-Sided) 95% -0.022 to 0.067 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.023 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Slopes, 95 percent CI and P-values were obtained from a random coefficients MMRM with random intercept and slope for each participant, and fixed effects for treatment group, time (years), a treatment group*time (years) interaction, geographic region, gender, age, and body mass index with an unstructured covariance matrix for the random effects. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.327 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in slopes |
| Estimated Value | 0.022 | |
| Confidence Interval |
(2-Sided) 95% -0.022 to 0.067 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.023 |
|
| Estimation Comments | ||
| Title | Rate of Progression of Joint Space Narrowing in Participants With Kellgren and Lawrence Grade Equal to (=) 3 |
|---|---|
| Description | Rate of progression of JSN was defined as narrowing in joint space width over the course of the study. It was measured radiographically in the medial tibiofemoral of knee of participants with OA. The slope reported in mm/year over a 2 year period was used to assess the rate of progression of JSN. KLG system was a method of classifying the severity of knee OA using five grades (0 [no severity] to 4 [maximum severity], higher grade indicating worse knee function). Negative values of slope indicating a worsening of osteoarthritis. |
| Time Frame | Baseline up to Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'N' signifies participants with KLG =3 and evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 238 | 256 | 240 |
| Mean (Standard Deviation) [mm/year] |
-0.133
(0.352)
|
-0.162
(0.319)
|
-0.136
(0.286)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Slopes, 95 percent CI and P-values were obtained from a random coefficients MMRM with random intercept and slope for each participant, and fixed effects for treatment group, time (years), a treatment group*time (years) interaction, geographic region, gender, age, and body mass index with an unstructured covariance matrix for the random effects. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.881 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in slopes |
| Estimated Value | 0.004 | |
| Confidence Interval |
(2-Sided) 95% -0.046 to 0.054 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.026 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Slopes, 95 percent CI and P-values were obtained from a random coefficients MMRM with random intercept and slope for each participant, and fixed effects for treatment group, time (years), a treatment group*time (years) interaction, geographic region, gender, age, and body mass index with an unstructured covariance matrix for the random effects. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.780 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in slopes |
| Estimated Value | -0.007 | |
| Confidence Interval |
(2-Sided) 95% -0.056 to 0.042 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.025 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index (WOMAC) Composite Index Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The WOMAC was a self-administered, disease-specific instrument which probed clinically important, participant relevant symptoms in the areas of pain, stiffness, and physical function in participants with OA of the knee. The WOMAC composite index was the sum of 24 individual questions regarding subscales of pain, stiffness and physical function (for each item score range: 0 [minimum] to 4 [maximum], higher score indicating worse knee condition). Total score was sum of the 3 subscale scores, giving a possible overall score range of 0 (minimum) to 96 (maximum). Higher score indicating the worse level of pain, stiffness and physical function. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 481) |
39.07
(18.85)
|
37.29
(17.98)
|
38.45
(18.91)
|
| Change at Month 3 (n =449, 450, 455) |
-5.35
(14.73)
|
-5.08
(13.14)
|
-5.50
(13.59)
|
| Change at Month 6 (n =424, 426, 433) |
-7.20
(15.99)
|
-5.84
(15.15)
|
-7.07
(15.62)
|
| Change at Month 12 (n =370, 388, 397) |
-9.17
(18.19)
|
-9.25
(15.82)
|
-9.84
(15.75)
|
| Change at Month 18 (n =344, 361, 357) |
-9.91
(17.98)
|
-8.35
(16.87)
|
-8.82
(18.00)
|
| Change at Month 24 (n =336, 339, 349) |
-10.85
(18.49)
|
-10.98
(17.62)
|
-10.49
(17.26)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.639 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.40 | |
| Confidence Interval |
(2-Sided) 95% -1.26 to 2.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.84 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.957 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% -1.61 to 1.70 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.84 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.893 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% -1.76 to 2.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.365 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% -1.01 to 2.76 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.678 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% -1.63 to 2.51 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.05 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.902 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.13 | |
| Confidence Interval |
(2-Sided) 95% -2.18 to 1.93 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.05 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.577 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.64 | |
| Confidence Interval |
(2-Sided) 95% -2.89 to 1.61 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.15 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.980 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.03 | |
| Confidence Interval |
(2-Sided) 95% -2.26 to 2.21 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.14 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.950 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.07 | |
| Confidence Interval |
(2-Sided) 95% -2.37 to 2.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.17 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.292 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.23 | |
| Confidence Interval |
(2-Sided) 95% -3.53 to 1.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.17 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Subscale Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The WOMAC pain subscale was comprised of 5 questions regarding the amount of pain experienced due to OA in the study knee. The WOMAC pain subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse pain. An overall subscale score range of 0 (minimum) to 20 (maximum), with higher scores indicating more pain. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =482, 484, 483) |
7.96
(3.94)
|
7.44
(3.87)
|
7.59
(4.03)
|
| Change at Month 3 (n =451, 453, 458) |
-1.32
(3.41)
|
-1.23
(3.19)
|
-1.25
(3.15)
|
| Change at Month 6 (n =426, 429, 435) |
-1.73
(3.73)
|
-1.42
(3.58)
|
-1.59
(3.45)
|
| Change at Month 12 (n =372, 389, 398) |
-2.17
(4.25)
|
-2.10
(3.66)
|
-2.08
(3.47)
|
| Change at Month 18 (n =347, 363, 359) |
-2.24
(4.16)
|
-2.00
(3.93)
|
-1.86
(3.88)
|
| Change at Month 24 (n =337, 342, 351) |
-2.48
(4.02)
|
-2.23
(4.16)
|
-2.19
(3.79)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group* visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.683 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.30 to 0.46 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.853 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.42 to 0.35 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group* visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.938 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.41 to 0.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.22 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.648 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 0.52 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.22 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.916 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.49 to 0.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.24 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.528 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.60 to 0.31 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.23 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.365 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.23 | |
| Confidence Interval |
(2-Sided) 95% -0.73 to 0.27 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.25 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.328 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.25 | |
| Confidence Interval |
(2-Sided) 95% -0.74 to 0.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.25 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.540 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 95% -0.66 to 0.35 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.26 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.423 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.21 | |
| Confidence Interval |
(2-Sided) 95% -0.71 to 0.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.26 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Pain Stiffness Subscale Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | Stiffness was defined as a sensation of decreased ease in which the participant moved the knee with OA. The WOMAC stiffness subscale was comprised of 2 questions regarding the degree of stiffness experienced in the study knee. The WOMAC stiffness subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse stiffness. An overall score range of 0 (minimum) to 8 (maximum), with higher scores indicating more stiffness. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 484, 482) |
3.48
(1.80)
|
3.33
(1.78)
|
3.44
(1.77)
|
| Change at Month 3 (n =449, 455, 456) |
-0.52
(1.67)
|
-0.51
(1.58)
|
-0.51
(1.58)
|
| Change at Month 6 (n =425, 429, 434) |
-0.67
(1.70)
|
-0.56
(1.78)
|
-0.62
(1.73)
|
| Change at Month 12 (n =371, 389, 397) |
-0.89
(1.89)
|
-0.79
(1.83)
|
-0.95
(1.78)
|
| Change at Month 18 (n =346, 363, 358) |
-0.88
(1.86)
|
-0.87
(1.88)
|
-0.82
(1.82)
|
| Change at Month 24 (n =336, 342, 349) |
-0.94
(1.95)
|
-1.10
(1.95)
|
-0.95
(1.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.904 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 0.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.582 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.24 to 0.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.818 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.22 to 0.18 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group x visit interaction, (collapsed) KLG, a (collapsed) KLG x visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.988 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.00 | |
| Confidence Interval |
(2-Sided) 95% -0.20 to 0.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.857 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.20 to 0.24 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.658 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 0.27 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.612 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.28 to 0.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.391 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.10 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 0.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.00 | |
| Confidence Interval |
(2-Sided) 95% -0.24 to 0.24 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.086 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.21 | |
| Confidence Interval |
(2-Sided) 95% -0.45 to 0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Western Ontario and MacMaster Osteoarthritis Index Physical Function Subscale Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The WOMAC physical function subscale referred to the participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was comprised of 17 questions regarding the degree of difficulty experienced due to OA in the study knee. The WOMAC physical function subscale score for each question ranged from 0 (minimum) to 4 (maximum), higher scores signified worse physical function. An overall score range of 0 (minimum) to 68 (maximum), with higher scores indicating worse physical function. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 482) |
27.63
(13.88)
|
26.49
(13.18)
|
27.39
(13.81)
|
| Change at Month 3 (n =449, 452, 456) |
-3.50
(10.77)
|
-3.24
(9.71)
|
-3.72
(9.99)
|
| Change at Month 6 (n =424, 426, 434) |
-4.78
(11.73)
|
-3.86
(10.81)
|
-4.82
(11.43)
|
| Change at Month 12 (n =370, 388, 398) |
-6.09
(13.21)
|
-6.37
(11.34)
|
-6.79
(11.55)
|
| Change at Month 18 (n =344, 361, 358) |
-6.74
(12.95)
|
-5.49
(12.05)
|
-6.12
(13.22)
|
| Change at Month 24 (n =336, 339, 350) |
-7.42
(13.47)
|
-7.65
(12.37)
|
-7.35
(12.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.586 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.34 | |
| Confidence Interval |
(2-Sided) 95% -0.88 to 1.55 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.789 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.17 | |
| Confidence Interval |
(2-Sided) 95% -1.05 to 1.38 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.821 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.16 | |
| Confidence Interval |
(2-Sided) 95% -1.21 to 1.52 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.294 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.73 | |
| Confidence Interval |
(2-Sided) 95% -0.63 to 2.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.532 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.48 | |
| Confidence Interval |
(2-Sided) 95% -1.02 to 1.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.76 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.938 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -1.55 to 1.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.76 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.680 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.34 | |
| Confidence Interval |
(2-Sided) 95% -1.97 to 1.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.730 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.28 | |
| Confidence Interval |
(2-Sided) 95% -1.33 to 1.90 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.901 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% -1.55 to 1.76 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.84 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.333 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.81 | |
| Confidence Interval |
(2-Sided) 95% -2.45 to 0.83 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.84 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Patient Assessment of Arthritic Pain Visual Analog Scale (VAS) Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | Pain VAS was a self-administered instrument, a 100 millimeter (mm) line marked by participant. Intensity of pain range (over past week): 0 (mm) =no pain to 100 (mm) =worst possible pain. Higher score indicating severe pain. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =478, 479, 482) |
40.19
(24.77)
|
37.59
(24.26)
|
39.37
(23.91)
|
| Change at Month 3 (n =446, 448, 455) |
-7.21
(25.49)
|
-7.02
(23.45)
|
-9.12
(21.72)
|
| Change at Month 6 (n =422, 424, 435) |
-10.13
(24.91)
|
-7.92
(24.90)
|
-10.17
(24.07)
|
| Change at Month 12 (n =370, 384, 396) |
-11.75
(30.38)
|
-10.98
(25.28)
|
-12.97
(24.26)
|
| Change at Month 18 (n =342, 360, 360) |
-13.99
(26.78)
|
-11.17
(25.60)
|
-12.86
(26.47)
|
| Change at Month 24 (n =333, 338, 348) |
-14.59
(28.36)
|
-13.36
(25.69)
|
-13.29
(23.97)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.086 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 2.34 | |
| Confidence Interval |
(2-Sided) 95% -0.33 to 5.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.415 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 95% -1.56 to 3.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.569 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.80 | |
| Confidence Interval |
(2-Sided) 95% -1.97 to 3.57 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.41 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.374 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.26 | |
| Confidence Interval |
(2-Sided) 95% -1.51 to 4.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.41 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.288 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.63 | |
| Confidence Interval |
(2-Sided) 95% -1.38 to 4.64 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.53 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.440 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.18 | |
| Confidence Interval |
(2-Sided) 95% -1.81 to 4.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.52 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.896 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.21 | |
| Confidence Interval |
(2-Sided) 95% -3.30 to 2.88 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.58 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.464 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.14 | |
| Confidence Interval |
(2-Sided) 95% -1.92 to 4.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.56 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.901 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.20 | |
| Confidence Interval |
(2-Sided) 95% -3.27 to 2.88 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.57 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value,geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.800 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.39 | |
| Confidence Interval |
(2-Sided) 95% -3.45 to 2.66 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.56 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Patient Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using the scale ranging from 1 (minimum) to 5 (maximum), where 1 =very good, 2 =good, 3 =fair, 4 =poor and 5 =very poor. Higher scores indicating worse condition. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 483) |
2.684
(0.904)
|
2.610
(0.883)
|
2.634
(0.883)
|
| Change at Month 3 (n =449, 452, 455) |
-0.232
(0.909)
|
-0.230
(0.816)
|
-0.202
(0.787)
|
| Change at Month 6 (n =424, 427, 435) |
-0.337
(0.876)
|
-0.319
(0.857)
|
-0.260
(0.879)
|
| Change at Month 12 (n =368, 385, 397) |
-0.405
(0.908)
|
-0.371
(0.930)
|
-0.370
(0.848)
|
| Change at Month 18 (n =344, 361, 358) |
-0.442
(0.979)
|
-0.418
(0.934)
|
-0.388
(0.903)
|
| Change at Month 24 (n =335, 340, 351) |
-0.513
(0.950)
|
-0.488
(0.939)
|
-0.473
(0.934)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.984 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.001 | |
| Confidence Interval |
(2-Sided) 95% -0.093 to 0.095 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.048 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.330 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.046 | |
| Confidence Interval |
(2-Sided) 95% -0.140 to 0.047 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.048 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.308 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.050 | |
| Confidence Interval |
(2-Sided) 95% -0.146 to 0.046 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.049 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.089 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.083 | |
| Confidence Interval |
(2-Sided) 95% -0.180 to 0.013 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.049 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.508 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.035 | |
| Confidence Interval |
(2-Sided) 95% -0.137 to 0.068 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.052 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.490 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.036 | |
| Confidence Interval |
(2-Sided) 95% -0.137 to 0.066 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.052 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.739 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.019 | |
| Confidence Interval |
(2-Sided) 95% -0.132 to 0.094 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.057 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.376 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.050 | |
| Confidence Interval |
(2-Sided) 95% -0.162 to 0.061 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.057 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.883 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.008 | |
| Confidence Interval |
(2-Sided) 95% -0.121 to 0.104 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.057 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.690 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.023 | |
| Confidence Interval |
(2-Sided) 95% -0.135 to 0.089 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.057 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Physician's Global Assessment of Arthritic Condition Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | Physician assessed the overall impact of arthritis on the participant's daily life. Participant's condition was rated by the physician using the scale ranging from 1 (minimum) to 5 (maximum), where 1= very good, 2= good, 3= fair, 4= poor and 5= very poor. Higher scores indicating worse condition. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =480, 483, 480) |
2.785
(0.679)
|
2.834
(0.689)
|
2.831
(0.655)
|
| Change at Month 3 (n =449, 448, 453) |
-0.379
(0.782)
|
-0.422
(0.756)
|
-0.415
(0.764)
|
| Change at Month 6 (n =420, 426, 431) |
-0.443
(0.823)
|
-0.561
(0.841)
|
-0.452
(0.791)
|
| Change at Month 12 (n =367, 386, 396) |
-0.548
(0.873)
|
-0.627
(0.859)
|
-0.535
(0.828)
|
| Change at Month 18 (n =342, 359, 355) |
-0.602
(0.906)
|
-0.643
(0.833)
|
-0.628
(0.862)
|
| Change at Month 24 (n = 331, 340, 349) |
-0.656
(0.906)
|
-0.662
(0.879)
|
-0.711
(0.867)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.849 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.008 | |
| Confidence Interval |
(2-Sided) 95% -0.078 to 0.095 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.044 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.837 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.009 | |
| Confidence Interval |
(2-Sided) 95% -0.096 to 0.078 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.044 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.776 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.013 | |
| Confidence Interval |
(2-Sided) 95% -0.105 to 0.078 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.047 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.100 | |
| Confidence Interval |
(2-Sided) 95% -0.191 to -0.008 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.047 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.201 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.064 | |
| Confidence Interval |
(2-Sided) 95% -0.163 to 0.034 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.050 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.103 | |
| Confidence Interval |
(2-Sided) 95% -0.201 to -0.006 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.050 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.848 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.010 | |
| Confidence Interval |
(2-Sided) 95% -0.114 to 0.094 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.053 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.714 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.019 | |
| Confidence Interval |
(2-Sided) 95% -0.122 to 0.084 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.052 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.652 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.025 | |
| Confidence Interval |
(2-Sided) 95% -0.082 to 0.131 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.054 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.700 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.021 | |
| Confidence Interval |
(2-Sided) 95% -0.085 to 0.127 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.054 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Pain After a 50-foot Walk Using Pain Visual Analog Scale Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The pain VAS following a 50 foot walk was a single-item, self-administered instrument. Participants were asked to assess the pain due to OA in their study knee after a 50-foot walk. Participants responded on a VAS scale ranging from 0 (no pain) to 100 (severe pain). Higher scores indicating more pain. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =480, 483, 482) |
38.03
(26.39)
|
35.13
(26.10)
|
38.00
(25.73)
|
| Change at Month 3 (n =446, 453, 456) |
-5.78
(25.30)
|
-5.71
(23.20)
|
-7.45
(23.15)
|
| Change at Month 6 (n =424, 428, 436) |
-8.13
(25.86)
|
-7.17
(25.42)
|
-8.78
(25.67)
|
| Change at Month 12 (n =370, 382, 397) |
-11.32
(27.42)
|
-10.07
(25.22)
|
-11.91
(24.04)
|
| Change at Month 18 (n = 345, 360, 357) |
-11.17
(27.51)
|
-8.91
(27.12)
|
-11.86
(26.04)
|
| Change at Month 24 (n =336, 340, 351) |
-12.31
(27.61)
|
-12.86
(26.73)
|
-13.77
(24.53)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.220 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.68 | |
| Confidence Interval |
(2-Sided) 95% -1.00 to 4.36 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.37 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.997 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 95% -2.67 to 2.68 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.613 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.73 | |
| Confidence Interval |
(2-Sided) 95% -2.09 to 3.55 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.44 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.964 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.06 | |
| Confidence Interval |
(2-Sided) 95% -2.75 to 2.88 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.44 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.872 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.24 | |
| Confidence Interval |
(2-Sided) 95% -2.69 to 3.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.49 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.947 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% -2.81 to 3.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.48 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.927 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.15 | |
| Confidence Interval |
(2-Sided) 95% -3.03 to 3.33 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.62 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.547 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 95% -2.18 to 4.12 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.61 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.304 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.62 | |
| Confidence Interval |
(2-Sided) 95% -1.47 to 4.71 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.58 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.679 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.65 | |
| Confidence Interval |
(2-Sided) 95% -3.73 to 2.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.57 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Total Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The OA pain and assessment tool-knee joint is also known as the intermittent and constant osteoarthritis pain (ICOAP) scale. The OA pain assessment tool-knee joint was an 11-item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. The total score was calculated by adding the 11 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse health. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluated for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =479, 480, 481) |
39.35
(23.06)
|
36.55
(21.78)
|
38.79
(22.29)
|
| Change at Month 3 (n =448, 450, 449) |
-7.00
(19.95)
|
-6.68
(17.77)
|
-7.08
(18.15)
|
| Change at Month 6 (n =422, 422, 430) |
-9.09
(21.43)
|
-7.74
(19.36)
|
-8.27
(19.68)
|
| Change at Month 12 (n = 365, 384, 397) |
-13.00
(21.93)
|
-10.84
(20.58)
|
-12.26
(20.24)
|
| Change at Month 18 (n =342, 359, 359) |
-12.71
(22.64)
|
-9.59
(21.26)
|
-11.23
(22.13)
|
| Change at Month 24 (n =330, 340, 349) |
-13.02
(22.30)
|
-12.87
(21.53)
|
-13.79
(21.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.738 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.37 | |
| Confidence Interval |
(2-Sided) 95% -1.80 to 2.55 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.11 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.632 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.53 | |
| Confidence Interval |
(2-Sided) 95% -2.70 to 1.64 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.11 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.736 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.41 | |
| Confidence Interval |
(2-Sided) 95% -2.77 to 1.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.21 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.811 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -2.66 to 2.08 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.21 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.335 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.22 | |
| Confidence Interval |
(2-Sided) 95% -3.71 to 1.26 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.27 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.966 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -2.52 to 2.41 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.26 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.299 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.44 | |
| Confidence Interval |
(2-Sided) 95% -4.16 to 1.28 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.38 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.925 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% -2.56 to 2.82 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.37 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.676 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.58 | |
| Confidence Interval |
(2-Sided) 95% -2.14 to 3.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.39 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.732 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.47 | |
| Confidence Interval |
(2-Sided) 95% -3.18 to 2.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.38 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Constant Pain Subscale Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The OA pain assessment tool-knee joint constant pain subscale was a 5 item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Overall subscale score was calculated by adding the 5 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse constant pain. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =479, 481, 484) |
35.25
(24.83)
|
33.01
(24.09)
|
35.21
(24.45)
|
| Change at Month 3 (n =448, 452, 454) |
-6.61
(21.64)
|
-6.41
(19.44)
|
-6.55
(19.92)
|
| Change at Month 6 (n =423, 426, 434) |
-7.88
(23.11)
|
-7.47
(21.05)
|
-8.25
(20.55)
|
| Change at Month 12 (n = 367, 384, 399) |
-11.78
(23.21)
|
-10.83
(21.94)
|
-11.75
(21.85)
|
| Change at Month 18 (n = 343, 360, 360) |
-11.63
(23.68)
|
-9.88
(22.01)
|
-10.62
(23.82)
|
| Change at Month 24 (n = 330, 340, 350) |
-11.59
(23.68)
|
-12.51
(23.17)
|
-13.15
(23.37)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.911 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.13 | |
| Confidence Interval |
(2-Sided) 95% -2.22 to 2.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.20 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.500 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.81 | |
| Confidence Interval |
(2-Sided) 95% -3.16 to 1.54 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.20 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.596 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.67 | |
| Confidence Interval |
(2-Sided) 95% -1.81 to 3.15 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.26 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.979 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.03 | |
| Confidence Interval |
(2-Sided) 95% -2.51 to 2.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.26 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.659 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.59 | |
| Confidence Interval |
(2-Sided) 95% -3.20 to 2.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.33 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.823 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.30 | |
| Confidence Interval |
(2-Sided) 95% -2.89 to 2.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.32 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.387 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.24 | |
| Confidence Interval |
(2-Sided) 95% -4.04 to 1.57 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.43 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.737 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.48 | |
| Confidence Interval |
(2-Sided) 95% -3.25 to 2.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.42 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.443 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.12 | |
| Confidence Interval |
(2-Sided) 95% -1.73 to 3.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.45 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.585 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.79 | |
| Confidence Interval |
(2-Sided) 95% -3.62 to 2.04 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.44 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Osteoarthritis Pain Assessment Tool-Knee Joint Intermittent Pain Subscale Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The OA pain assessment tool-knee joint intermittent pain subscale score a 6 item scale, with each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Overall subscale score was calculated by adding the 6 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse intermittent pain. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =479, 480, 481) |
42.76
(22.85)
|
39.44
(21.46)
|
41.73
(22.10)
|
| Change at Month 3 (n =448, 450, 450) |
-7.32
(20.68)
|
-6.93
(18.95)
|
-7.48
(19.28)
|
| Change at Month 6 (n =422, 422, 430) |
-10.18
(22.28)
|
-7.96
(20.34)
|
-8.31
(21.44)
|
| Change at Month 12 (n =365, 385, 397) |
-14.15
(22.93)
|
-10.93
(21.86)
|
-12.54
(21.64)
|
| Change at Month 18 (n =342, 359, 359) |
-13.56
(23.72)
|
-9.45
(23.07)
|
-11.69
(23.02)
|
| Change at Month 24 (n =330, 340, 349) |
-14.20
(23.11)
|
-13.17
(22.74)
|
-14.27
(22.66)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.613 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.58 | |
| Confidence Interval |
(2-Sided) 95% -1.68 to 2.85 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.16 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.670 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.49 | |
| Confidence Interval |
(2-Sided) 95% -2.76 to 1.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.16 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.296 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.33 | |
| Confidence Interval |
(2-Sided) 95% -3.82 to 1.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.27 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.604 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.66 | |
| Confidence Interval |
(2-Sided) 95% -3.15 to 1.83 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.27 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.163 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.86 | |
| Confidence Interval |
(2-Sided) 95% -4.46 to 0.75 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.33 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.939 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.10 | |
| Confidence Interval |
(2-Sided) 95% -2.69 to 2.48 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.32 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.233 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.74 | |
| Confidence Interval |
(2-Sided) 95% -4.61 to 1.12 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.46 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.720 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) 95% -2.32 to 3.36 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.45 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.993 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 95% -2.82 to 2.85 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.45 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.794 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.38 | |
| Confidence Interval |
(2-Sided) 95% -3.19 to 2.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.44 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Osteoarthritis Research Society International (OARSI) Knee Function Survey Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The OARSI knee function survey was an 11-item scale with each item scored 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. The total score was the sum of the 11 items and ranged from 0 (minimum) to 44 (maximum), where higher scores indicating worse health condition. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =382, 376, 391) |
22.19
(8.96)
|
21.49
(8.59)
|
21.80
(8.92)
|
| Change at Month 3 (n = 309, 304, 315) |
-2.20
(7.70)
|
-2.24
(6.57)
|
-2.99
(7.12)
|
| Change at Month 6 (n =270, 283, 294) |
-3.24
(8.42)
|
-3.29
(7.80)
|
-3.53
(8.26)
|
| Change at Month 12 (n =240, 263, 266) |
-4.57
(8.65)
|
-4.35
(7.76)
|
-4.46
(7.99)
|
| Change at Month 18 (n =225, 239, 243) |
-5.14
(9.37)
|
-4.61
(8.56)
|
-4.93
(9.22)
|
| Change at Month 24(n = 227, 224, 237) |
-5.31
(9.40)
|
-5.13
(8.36)
|
-5.62
(9.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.069 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 95% -0.07 to 2.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.335 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) 95% -0.53 to 1.57 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.153 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% -0.33 to 2.11 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.672 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.95 to 1.47 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.765 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.19 | |
| Confidence Interval |
(2-Sided) 95% -1.05 to 1.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.63 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.675 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.96 to 1.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.560 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.42 | |
| Confidence Interval |
(2-Sided) 95% -1.00 to 1.84 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.433 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% -0.84 to 1.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.318 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.73 | |
| Confidence Interval |
(2-Sided) 95% -0.70 to 2.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.303 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to 2.18 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Knee Injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS) Score at Month 3, 6, 12, 18 and 24 |
|---|---|
| Description | The KOOS-PS was used to rate participant's opinions about the difficulties they experienced with activity due to problems with their knee. It was a 7-item scale, each item scored from 0 (minimum) to 4 (maximum), where 4 indicated worst health condition. Total score was calculated by adding the responses to 7 items and rescaled to a 0 (minimum) to 100 (maximum) scale, where higher scores indicating worse health condition. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =432, 423, 428) |
42.75
(14.69)
|
41.82
(13.85)
|
42.60
(14.76)
|
| Change at Month 3 (n =376, 363, 370) |
-3.50
(12.68)
|
-4.31
(11.38)
|
-5.23
(11.47)
|
| Change at Month 6 (n =336, 335, 348) |
-5.42
(13.70)
|
-5.41
(13.93)
|
-6.03
(14.02)
|
| Change at Month 12 (n =288, 315, 320) |
-7.01
(14.60)
|
-7.67
(13.26)
|
-7.32
(13.52)
|
| Change at Month 18 (n =284, 284, 280) |
-8.10
(16.00)
|
-7.44
(14.09)
|
-7.47
(15.00)
|
| Change at Month 24 (n =272, 272, 278) |
-8.49
(16.06)
|
-9.01
(14.74)
|
-9.60
(15.48)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLGU*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.039 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.67 | |
| Confidence Interval |
(2-Sided) 95% 0.08 to 3.26 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.81 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 3; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.395 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.70 | |
| Confidence Interval |
(2-Sided) 95% -0.91 to 2.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.160 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.36 | |
| Confidence Interval |
(2-Sided) 95% -0.54 to 3.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 6; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.638 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.46 | |
| Confidence Interval |
(2-Sided) 95% -1.44 to 2.35 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.97 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.537 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.61 | |
| Confidence Interval |
(2-Sided) 95% -1.32 to 2.54 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.98 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*(visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.988 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 95% -1.90 to 1.93 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.98 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.962 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% -2.12 to 2.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.11 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 18; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.856 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.20 | |
| Confidence Interval |
(2-Sided) 95% -1.97 to 2.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.11 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.237 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.36 | |
| Confidence Interval |
(2-Sided) 95% -0.90 to 3.63 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.15 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.475 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.82 | |
| Confidence Interval |
(2-Sided) 95% -1.44 to 3.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.15 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 (SF-36) Physical Functioning Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 16.18 (minimum) to 57.11 (maximum), with higher scores indicating better physical functioning. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 485) |
35.67
(9.74)
|
36.84
(9.42)
|
36.32
(9.15)
|
| Change at Month 12 (n =368, 381, 397) |
2.59
(8.80)
|
2.41
(8.66)
|
2.55
(8.84)
|
| Change at Month 24 (n =332, 341, 352) |
3.53
(9.50)
|
3.23
(9.66)
|
3.51
(9.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.938 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.04 | |
| Confidence Interval |
(2-Sided) 95% -1.07 to 1.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.906 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.07 | |
| Confidence Interval |
(2-Sided) 95% -1.04 to 1.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.726 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.23 | |
| Confidence Interval |
(2-Sided) 95% -1.50 to 1.04 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.681 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -1.52 to 1.00 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.64 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Role - Physical Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 18.45 (minimum) to 56.62 (maximum), with higher scores indicating better role-physical. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 485) |
39.99
(9.85)
|
40.37
(9.73)
|
40.14
(10.03)
|
| Change at Month 12 (n =368, 381, 397) |
2.06
(9.55)
|
2.35
(8.75)
|
2.22
(8.85)
|
| Change at Month 24 (n =333, 341, 352) |
2.44
(9.53)
|
2.44
(9.34)
|
2.70
(9.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.900 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.07 | |
| Confidence Interval |
(2-Sided) 95% -1.07 to 1.21 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.528 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.36 | |
| Confidence Interval |
(2-Sided) 95% -0.77 to 1.50 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.647 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -1.51 to 0.94 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.841 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -1.34 to 1.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Bodily Pain Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 19.23 (minimum) to 60.88 (maximum), with higher scores indicating lower bodily pain. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 485) |
38.81
(8.63)
|
39.77
(8.34)
|
38.90
(8.22)
|
| Change at Month 12 (n =368, 381, 397) |
4.07
(9.64)
|
3.72
(8.32)
|
4.06
(8.97)
|
| Change at Month 24 (n =332, 341, 352) |
4.25
(9.54)
|
4.65
(9.90)
|
4.46
(9.44)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.587 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.32 | |
| Confidence Interval |
(2-Sided) 95% -0.84 to 1.48 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.59 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.687 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.24 | |
| Confidence Interval |
(2-Sided) 95% -0.91 to 1.38 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.677 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.27 | |
| Confidence Interval |
(2-Sided) 95% -1.56 to 1.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.469 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.47 | |
| Confidence Interval |
(2-Sided) 95% -0.80 to 1.74 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 General Health Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 16.75 (minimum) to 63.72 (maximum), with higher scores indicating better general health. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 481, 484) |
44.77
(10.15)
|
46.49
(9.79)
|
45.19
(9.63)
|
| Change at Month 12 (n =367, 381, 395) |
1.33
(7.52)
|
1.10
(7.64)
|
1.20
(6.93)
|
| Change at Month 24 (n =331, 341, 352) |
1.13
(8.43)
|
0.40
(7.76)
|
1.25
(7.77)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.632 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.23 | |
| Confidence Interval |
(2-Sided) 95% -0.71 to 1.17 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.48 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.308 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.49 | |
| Confidence Interval |
(2-Sided) 95% -0.45 to 1.42 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.48 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.615 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.27 | |
| Confidence Interval |
(2-Sided) 95% -1.33 to 0.79 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.425 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.43 | |
| Confidence Interval |
(2-Sided) 95% -1.48 to 0.62 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Vitality Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 22.02 (minimum) to 69.92 (maximum), with higher scores indicating better vitality. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 481, 484) |
47.57
(9.44)
|
49.00
(9.20)
|
48.08
(9.53)
|
| Change at Month 12 (n =368, 381, 396) |
1.52
(8.51)
|
0.48
(8.04)
|
1.04
(8.22)
|
| Change at Month 24 (n =332, 340, 351) |
1.53
(8.71)
|
0.78
(8.62)
|
1.42
(8.70)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.214 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.67 | |
| Confidence Interval |
(2-Sided) 95% -0.39 to 1.72 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.980 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.01 | |
| Confidence Interval |
(2-Sided) 95% -1.06 to 1.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.575 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.33 | |
| Confidence Interval |
(2-Sided) 95% -0.83 to 1.49 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.59 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.986 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.01 | |
| Confidence Interval |
(2-Sided) 95% -1.16 to 1.14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.59 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Social Functioning Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 13.38 (minimum) to 56.40 (maximum), with higher scores indicating better social functioning. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 485) |
45.15
(11.06)
|
46.23
(10.19)
|
45.64
(10.36)
|
| Change at Month 12 (n =368, 381, 397) |
1.11
(10.28)
|
-0.28
(9.16)
|
-0.15
(9.74)
|
| Change at Month 24 (n =333, 341, 352) |
1.31
(10.62)
|
0.88
(10.15)
|
0.12
(10.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.030 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.33 | |
| Confidence Interval |
(2-Sided) 95% 0.13 to 2.52 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.480 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.43 | |
| Confidence Interval |
(2-Sided) 95% -0.76 to 1.61 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.60 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.132 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.01 | |
| Confidence Interval |
(2-Sided) 95% -0.30 to 2.32 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.67 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.117 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.04 | |
| Confidence Interval |
(2-Sided) 95% -0.26 to 2.34 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Role-Emotional Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 10.25 (minimum) to 55.68 (maximum), with higher scores indicating better role-emotional. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 482, 485) |
43.73
(12.79)
|
43.27
(12.09)
|
43.37
(12.35)
|
| Change at Month 12 (n =368, 381, 396) |
0.05
(12.06)
|
-0.18
(10.55)
|
-0.25
(11.47)
|
| Change at Month 24 (n =333, 341, 352) |
-0.28
(12.77)
|
0.60
(11.69)
|
0.32
(11.98)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.133 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.06 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 2.44 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.71 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.524 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% -0.93 to 1.82 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.743 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 95% -1.27 to 1.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.78 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.310 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.78 | |
| Confidence Interval |
(2-Sided) 95% -0.73 to 2.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.77 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Mental Health Domain Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 8.02 (minimum) to 63.43 (maximum), with higher scores indicating better mental health. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 481, 484) |
47.01
(10.80)
|
47.70
(10.73)
|
47.26
(11.15)
|
| Change at Month 12 (n =368, 381, 396) |
0.95
(10.08)
|
0.19
(9.10)
|
-0.31
(9.50)
|
| Change at Month 24 (n =332, 340, 351) |
1.12
(10.26)
|
0.26
(10.01)
|
-0.01
(9.81)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.058 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.17 | |
| Confidence Interval |
(2-Sided) 95% -0.04 to 2.38 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.213 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.76 | |
| Confidence Interval |
(2-Sided) 95% -0.44 to 1.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.143 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.98 | |
| Confidence Interval |
(2-Sided) 95% -0.33 to 2.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.67 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.450 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 95% -0.80 to 1.81 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.67 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Physical Health Component Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 22.88 (minimum) to 58.69 (maximum), with higher scores indicating better physical health. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 480, 483) |
37.38
(8.84)
|
38.69
(8.35)
|
37.84
(8.46)
|
| Change at Month 12 (n =367, 381, 395) |
3.26
(7.98)
|
3.31
(7.69)
|
3.58
(7.87)
|
| Change at Month 24 (n =329, 340, 351) |
3.77
(8.48)
|
3.66
(8.32)
|
4.18
(8.48)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.701 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.20 | |
| Confidence Interval |
(2-Sided) 95% -1.19 to 0.80 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.764 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.84 to 1.14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.228 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.68 | |
| Confidence Interval |
(2-Sided) 95% -1.80 to 0.43 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit,a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.514 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.37 | |
| Confidence Interval |
(2-Sided) 95% -1.47 to 0.74 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Short Form-36 Mental Health Component Score at Month 12 and 24 |
|---|---|
| Description | The SF-36 was a participant administered scale assessing general quality of life. It consisted of self-administered 36-item questionnaire that measured 8 health domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. These 8 domains were also summarized as physical and mental component scores. The score for each domain and component score was the mean of the individual question scores, which were scaled from 0 (minimum) to 100 (maximum), where higher scores indicated highest level of health/functioning. Linear transformations were performed to transform scores and rescaled to a score range of 11.11 (minimum) to 61.67 (maximum), with higher scores indicating better mental health. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =481, 480, 483) |
49.65
(11.79)
|
49.97
(11.11)
|
49.65
(11.62)
|
| Change at Month 12 (n =367, 381, 395) |
-0.13
(10.64)
|
-1.17
(9.48)
|
-1.27
(9.65)
|
| Change at Month 24 (n =329, 340, 351) |
-0.41
(11.24)
|
-0.70
(10.08)
|
-1.09
(10.18)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.023 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.42 | |
| Confidence Interval |
(2-Sided) 95% 0.19 to 2.65 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.391 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to 1.75 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.142 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.02 | |
| Confidence Interval |
(2-Sided) 95% -0.34 to 2.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.204 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% -0.47 to 2.21 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | ||
| Title | Number of Participants With EuroQoL-5D (EQ-5D) Mobility Domain Score |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D mobility domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problem), 2 =moderate health (some problems) and 3 =worst health (confined to bed). Higher scores indicating worse health condition. Participants with EQ-5D mobility domain score were reported in this measure. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline: No problem (n =481, 481, 485) |
132
27.2%
|
135
27.8%
|
163
33.5%
|
| Baseline: Some problems (n =481, 481, 485) |
348
71.8%
|
345
71%
|
322
66.3%
|
| Baseline: Confined to bed (n =481, 481, 485) |
1
0.2%
|
1
0.2%
|
0
0%
|
| Month 12: No problem (n =371, 382, 399) |
174
35.9%
|
186
38.3%
|
178
36.6%
|
| Month 12: Some problems (n =371, 382, 399) |
197
40.6%
|
196
40.3%
|
221
45.5%
|
| Month 12: Confined to bed (n =371, 382, 399) |
0
0%
|
0
0%
|
0
0%
|
| Month 24: No problem (n =334, 341, 353) |
167
34.4%
|
161
33.1%
|
178
36.6%
|
| Month 24: Some problems (n =334, 341, 353) |
165
34%
|
180
37%
|
175
36%
|
| Month 24: Confined to bed (n =334, 341, 353) |
2
0.4%
|
0
0%
|
0
0%
|
| Title | Number of Participants With EuroQoL-5D Self-Care Domain Score |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D self-care domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problems with self-care), 2 =moderate health (some problems) and 3 =worst health (unable to wash or dress). Higher scores indicating worse health condition. Participants with EQ-5D self-care domain score were reported in this measure. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline: No problem (n =480, 481, 485) |
383
79%
|
387
79.6%
|
386
79.4%
|
| Baseline: Some problems (n =480, 481, 485) |
92
19%
|
93
19.1%
|
97
20%
|
| Baseline: Unable to wash/dress (n =480, 481, 485) |
5
1%
|
1
0.2%
|
2
0.4%
|
| Month 12: No problem (n =371, 382, 399) |
305
62.9%
|
327
67.3%
|
331
68.1%
|
| Month 12: Some problems (n =371, 382, 399) |
66
13.6%
|
51
10.5%
|
67
13.8%
|
| Month 12: Unable to wash/dress (n =371, 382, 399) |
0
0%
|
4
0.8%
|
1
0.2%
|
| Month 24: No problem (n =334, 341, 352) |
280
57.7%
|
286
58.8%
|
299
61.5%
|
| Month 24: Some problems (n =334, 341, 352) |
54
11.1%
|
55
11.3%
|
51
10.5%
|
| Month 24: Unable to wash/dress (n =334, 341, 352) |
0
0%
|
0
0%
|
2
0.4%
|
| Title | Number of Participants With EuroQoL-5D Usual Activity Domain Score |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D usual activity domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no problems), 2 =moderate health (some problems) and 3 =worst health state (unable to perform usual activities). Higher scores indicating worse health condition. Participants with EQ-5D usual activity domain score were reported in this measure. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline: No problem (n =481, 481, 485) |
186
38.4%
|
185
38.1%
|
190
39.1%
|
| Baseline: Some problems (n =481, 481, 485) |
285
58.8%
|
291
59.9%
|
289
59.5%
|
| Baseline: Unable to do activities(n=481,481,485) |
10
2.1%
|
5
1%
|
6
1.2%
|
| Month 12: No problem (n =371, 382, 399) |
192
39.6%
|
201
41.4%
|
193
39.7%
|
| Month 12: Some problems (n =371, 382, 399) |
176
36.3%
|
180
37%
|
204
42%
|
| Month 12: Unable to do activities(n =371,382,399) |
3
0.6%
|
1
0.2%
|
2
0.4%
|
| Month 24: No problem (n =334, 340, 352) |
187
38.6%
|
186
38.3%
|
205
42.2%
|
| Month 24: Some problems (n =334, 340, 352) |
140
28.9%
|
151
31.1%
|
144
29.6%
|
| Month 24: Unable to do activities(n =334,340,352) |
7
1.4%
|
3
0.6%
|
3
0.6%
|
| Title | Number of Participants With EuroQo-5D Pain and Discomfort Domain Score |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression. EQ-5D pain and discomfort domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (no pain and discomfort), 2 =moderate health (moderate pain and discomfort) and 3 =worst health state (extreme pain and discomfort). Higher scores indicated worse health condition. Participants with EQ-5D pain and discomfort domain score were reported in this measure. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline: None (n =481, 481, 485) |
42
8.7%
|
48
9.9%
|
38
7.8%
|
| Baseline: Moderate (n =481, 481, 485) |
383
79%
|
391
80.5%
|
403
82.9%
|
| Baseline: Extreme (n =481, 481, 485) |
56
11.5%
|
42
8.6%
|
44
9.1%
|
| Month 12: None (n =371, 382, 399) |
91
18.8%
|
89
18.3%
|
82
16.9%
|
| Month 12: Moderate (n =371, 382, 399) |
259
53.4%
|
280
57.6%
|
293
60.3%
|
| Month 12: Extreme (n =371, 382, 399) |
21
4.3%
|
13
2.7%
|
24
4.9%
|
| Month 24: None (n =334, 341, 352) |
92
19%
|
89
18.3%
|
98
20.2%
|
| Month 24: Moderate (n =334, 341, 352) |
226
46.6%
|
232
47.7%
|
240
49.4%
|
| Month 24: Extreme (n =334, 341, 352) |
16
3.3%
|
20
4.1%
|
14
2.9%
|
| Title | Number of Participants With EuroQoL-5D Anxiety and Depression Domain Score |
|---|---|
| Description | EQ-5D: participant rated questionnaire to assess health-related quality of life. Health state profile component assessed level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. EQ-5D anxiety and depression domain score scale ranged from 1 (minimum) to 3 (maximum), where 1 =better health (not anxious, depressed), 2 =moderate health (moderately anxious, depressed) and 3 =worst health (extremely anxious, depressed). Higher scores indicating worse health condition. Participants with EQ-5D anxiety and depression domain score were reported in this measure. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline: None (n =481, 481, 485) |
297
61.2%
|
306
63%
|
303
62.3%
|
| Baseline: Moderate (n =481, 481, 485) |
166
34.2%
|
164
33.7%
|
168
34.6%
|
| Baseline: Extreme (n =481, 481, 485) |
18
3.7%
|
11
2.3%
|
14
2.9%
|
| Month 12: None (n =371, 382, 399) |
251
51.8%
|
256
52.7%
|
261
53.7%
|
| Month 12: Moderate (n =371, 382, 399) |
111
22.9%
|
116
23.9%
|
127
26.1%
|
| Month12: Extreme (n =371, 382, 399) |
9
1.9%
|
10
2.1%
|
11
2.3%
|
| Month 24: None (n =334, 341, 352) |
235
48.5%
|
244
50.2%
|
237
48.8%
|
| Month 24: Moderate (n =334, 341, 352) |
93
19.2%
|
89
18.3%
|
109
22.4%
|
| Month 24: Extreme (n =334, 341, 352) |
6
1.2%
|
8
1.6%
|
6
1.2%
|
| Title | EuroQoL-5D Visual Analog Scale Score |
|---|---|
| Description | The EQ-5D VAS score was a participant rated questionnaire to assess health-related quality of life in terms of a single index value. It was a visual analogue scale that ranged from 0 (minimum) to 100 (maximum), with higher scores indicating a better health condition. |
| Time Frame | Baseline, Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Baseline (n =480, 479, 484) |
66.75
(21.52)
|
68.59
(19.69)
|
67.86
(19.36)
|
| Month 12 (n =369, 381, 399) |
72.34
(19.01)
|
72.55
(19.48)
|
70.58
(19.91)
|
| Month 24 (n =334, 341, 352) |
73.18
(19.64)
|
73.95
(18.85)
|
72.36
(19.36)
|
| Title | Number of Participants With Increase in Total Analgesic Medication Use |
|---|---|
| Description | Increase in total analgesic medication use for OA in the study knee was a comparison back to baseline of an increased and sustained use of standard background and/or rescue medication for more than 28 days as measured at the Month 12 and 24 visits. Only medications for OA knee pain were considered. |
| Time Frame | Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Month 12 (n =372, 395, 408) |
21
4.3%
|
29
6%
|
24
4.9%
|
| Month 24 (n =344, 353, 354) |
24
4.9%
|
34
7%
|
30
6.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; Odds ratio (OR), 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.875 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.952 | |
| Confidence Interval |
(2-Sided) 95% 0.516 to 1.756 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.406 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.273 | |
| Confidence Interval |
(2-Sided) 95% 0.721 to 2.247 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.406 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.787 | |
| Confidence Interval |
(2-Sided) 95% 0.448 to 1.384 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.591 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.154 | |
| Confidence Interval |
(2-Sided) 95% 0.685 to 1.942 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Decrease in Total Analgesic Medication Use |
|---|---|
| Description | Decrease in total analgesic medication use for OA in the study knee was a comparison back to baseline of a decreased and irregular use of standard background and/or rescue medication for more than 28 days as measured at the Month 12 and 24 visits. Only medications for OA knee pain were considered. |
| Time Frame | Month 12, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 485 | 486 | 486 |
| Month 12 (n =372, 395, 408) |
29
6%
|
38
7.8%
|
43
8.8%
|
| Month 24 (n =344, 353, 354) |
29
6%
|
38
7.8%
|
47
9.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 12; Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.168 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.704 | |
| Confidence Interval |
(2-Sided) 95% 0.428 to 1.160 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 12; Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.634 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.893 | |
| Confidence Interval |
(2-Sided) 95% 0.560 to 1.423 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Month 24; Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.032 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.583 | |
| Confidence Interval |
(2-Sided) 95% 0.356 to 0.955 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Month 24; Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.276 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.774 | |
| Confidence Interval |
(2-Sided) 95% 0.489 to 1.227 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Patient Global Impression of Change Score |
|---|---|
| Description | Patient global impression of change was a participant-rated instrument that measured change in participant's overall status on a 7-point scale ranging from: 1 =very much improved, 2 =much improved, 3 =minimally improved, 4 =no change, 5 =minimally worse, 6 =much worse and 7 =very much worse. Higher scores indicating worse condition. |
| Time Frame | Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'N' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 434 | 426 | 434 |
| Mean (Standard Deviation) [units on a scale] |
2.97
(1.26)
|
3.02
(1.34)
|
3.00
(1.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | LS Mean, 95 percent CI and P-values were obtained from an analysis of covariance (ANCOVA) model, with treatment group, (collapsed) KLG, geographic region, and gender as factors and age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.709 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.21 to 0.14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | LS-Mean, 95 percent CI and P-values were obtained from an ANCOVA model, with treatment group, (collapsed) KLG, geographic region, and gender as factors and age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.798 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.15 to 0.20 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | ||
| Title | Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index |
|---|---|
| Description | The OMERACT-OARSI responder index was used to determine whether participants may be considered responders to treatment. An OMERACT-OARSI responder was a participant who had a better response on the WOMAC pain subscale score, a better response on the WOMAC physical function subscale score or improvement on at least two of the three domains: WOMAC pain subscale score (overall score range of 0 [minimum] to 20 [maximum], higher scores indicating more pain), WOMAC physical function subscale score (overall score range of 0 [minimum] to 68 [maximum], higher scores indicating worse physical function) and patient global assessment of arthritic condition score (overall score range of 1 [minimum] to 5 [maximum], higher scores indicating worse condition). Number of participants who were OMERACT-OARSI responder were reported in this measure. |
| Time Frame | Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'N' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 468 | 469 | 470 |
| Number [participants] |
222
45.8%
|
226
46.5%
|
219
45.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, baseline JSW, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.810 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.032 | |
| Confidence Interval |
(2-Sided) 95% 0.797 to 1.337 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, baseline JSW, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.620 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.068 | |
| Confidence Interval |
(2-Sided) 95% 0.824 to 1.383 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Joint Space Narrowing Progression |
|---|---|
| Description | JSN progressor was defined as a participant with a decrease in joint space width that was greater in magnitude than the smallest detectable difference (0.199 mm). |
| Time Frame | Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'N' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 419 | 423 | 429 |
| Number [participants] |
136
28%
|
153
31.5%
|
165
34%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.047 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.745 | |
| Confidence Interval |
(2-Sided) 95% 0.557 to 0.997 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.317 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.864 | |
| Confidence Interval |
(2-Sided) 95% 0.650 to 1.150 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Applicable for Virtual Joint Replacement |
|---|---|
| Description | A virtual joint replacement candidate was defined as a participant whose last two WOMAC pain subscale scores (overall score range of 0 [minimum] to 20 [maximum], higher scores indicating more pain) were at least 8, last two WOMAC physical function subscale scores (overall score range of 0 [minimum] to 68 [maximum], higher scores indicating worse physical function) were at least 28 and was a joint space narrowing progressor (a participant with a decrease in JSW that was greater in magnitude than the smallest detectable difference =0.199 mm). |
| Time Frame | Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants randomized to the study. Here, 'N' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 405 | 411 | 425 |
| Number [participants] |
28
5.8%
|
34
7%
|
28
5.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.881 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.043 | |
| Confidence Interval |
(2-Sided) 95% 0.602 to 1.806 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Odds ratio, 95 percent CI and P-values were obtained from a logistic regression model, with treatment group, (collapsed) KLG, geographic region, and gender as factors, age and body mass index as covariates. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.525 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.186 | |
| Confidence Interval |
(2-Sided) 95% 0.701 to 2.009 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 7-10 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Adverse events included both serious and non-serious adverse events. |
| Time Frame | Baseline up to 7-10 days after last dose of study drug (Week 111) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants in the FAS who received at least 1 dose of the randomized study medication. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 482 | 485 | 485 |
| Adverse events |
371
76.5%
|
381
78.4%
|
364
74.9%
|
| Serious adverse events |
43
8.9%
|
61
12.6%
|
49
10.1%
|
| Title | Number of Participants With Electrocardiogram (ECG) Abnormalities |
|---|---|
| Description | Atrial (enlargement, fibrillation, premature beat), axis deviation, atrioventricular (accelerated conduction, first/second degree block), left anterior and posterior hemiblock, left atrial hypertrophy, left and right (complete/incomplete bundle branch block, ventricular hypertrophy), QRS (high/low voltage, nonspecific, prolongation greater than [>]140 milliseconds [msec]), junctional/paced rhythm, intraventricular conduction delay (>120 msec), early repolarization, ventricular premature contraction and beat, prolonged QTC, sinus (arrhythmia, bradycardia/tachycardia), supraventricular extra systole and premature beat, short PR syndrome. Abnormal Q-wave (>=30 msec), P-wave left/right atrial abnormality, T-wave flattened/inverted abnormality, U-wave abnormality, ST-T indeterminate abnormality, ST-T nonspecific changes, ST-T changes compatible with ischemia and pericarditis. ECG findings were judged by investigators for qualitative evaluation of abnormalities. |
| Time Frame | Baseline, Month 3, 6, 12, 18, 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants in the FAS who received at least 1 dose of the randomized study medication. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 482 | 485 | 485 |
| Baseline (n =481, 484, 485) |
0
0%
|
0
0%
|
1
0.2%
|
| Month 6 (n =414, 427, 427) |
3
0.6%
|
0
0%
|
1
0.2%
|
| Month 12 (n =373 , 397, 403) |
4
0.8%
|
1
0.2%
|
2
0.4%
|
| Month 18 (n =351, 366, 362) |
2
0.4%
|
2
0.4%
|
6
1.2%
|
| Month 24 (n =338, 344, 351) |
3
0.6%
|
1
0.2%
|
6
1.2%
|
| Title | Number of Participants With Laboratory Test Abnormalities |
|---|---|
| Description | Criteria for laboratory abnormalities: Hemoglobin (Hgb), hematocrit (hct), red blood cell(RBC) count: less than(<)0.8*lower limit of normal(LLN), platelet: <0.5*LLN or greater than (>)1.75*upper limit of normal (ULN), white blood cell (WBC): <0.6*LLN or >1.5*ULN, lymphocyte, neutrophil:<0.8*LLN or >1.2*ULN, basophil, eosinophil, monocyte:>1.2*ULN; total bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, gammaglutamyl transferase, alkaline phosphatase:> 3.0*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN; blood urea nitrogen, creatinine:>1.3*ULN, uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, magnesium, bicarbonate: <0.9*LLN or >1.1*ULN, phosphate <0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN, lipase >1.5*ULN; urine (specific gravity <1.003 or >1.030, pH <4.5 or >8, glucose, ketones, protein, blood/Hgb greater than or equal to [>=]1); pancreatic amylase >1.5*ULN. |
| Time Frame | Baseline up to Week 111 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants in the FAS who received at least 1 dose of the randomized study medication. Here, 'N' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 479 | 480 | 481 |
| Number [participants] |
289
59.6%
|
297
61.1%
|
288
59.3%
|
| Title | Change From Baseline in Systolic Blood Pressure (SBP) at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96 |
|---|---|
| Description | Blood pressure (BP) was measured by sphygmomanometer while participant was in supine position. Conditions were kept constant from visit to visit including observer, participant's same arm, cuff size, supine position, location, temperature, noise level. The same size BP cuff which was properly sized and calibrated, was used to measure BP each time. |
| Time Frame | Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants in the FAS who received at least 1 dose of the study medication. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 482 | 485 | 485 |
| Baseline (n =482, 485, 485) |
127.04
(12.42)
|
127.45
(12.18)
|
127.45
(12.32)
|
| Change at Week 2 (n =459, 466, 462) |
-0.06
(9.76)
|
0.82
(10.66)
|
-0.01
(10.71)
|
| Change at Week 4 (n =467, 467, 465) |
-1.08
(11.37)
|
0.99
(11.12)
|
-0.94
(10.73)
|
| Change at Week 12 (n =450, 455, 461) |
-0.11
(11.59)
|
1.74
(12.09)
|
-0.76
(12.33)
|
| Change at Week 24 (n =425, 432, 439) |
-0.47
(12.07)
|
0.97
(12.14)
|
-0.73
(11.46)
|
| Change at Week 36 (n =385, 415, 418) |
-0.11
(11.98)
|
-0.80
(12.02)
|
-1.58
(12.99)
|
| Change at Week 48 (n =377, 400, 410) |
-0.83
(12.36)
|
-0.22
(11.39)
|
-0.28
(12.01)
|
| Change at Week 60 (n =360, 377, 384) |
-1.02
(12.38)
|
0.33
(12.02)
|
-1.36
(12.24)
|
| Change at Week 72 (n =357, 374, 370) |
-0.82
(12.94)
|
-0.15
(13.00)
|
-0.20
(13.00)
|
| Change at Week 84 (n =346, 366, 362) |
-1.43
(13.45)
|
-0.77
(12.98)
|
-1.15
(13.08)
|
| Change at Week 96 (n =344, 353, 356) |
-0.55
(12.84)
|
0.02
(12.52)
|
-0.71
(12.79)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 2; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.668 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.27 | |
| Confidence Interval |
(2-Sided) 95% -1.50 to 0.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.63 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 2; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.326 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.62 | |
| Confidence Interval |
(2-Sided) 95% -0.61 to 1.85 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.63 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 4; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.679 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.27 | |
| Confidence Interval |
(2-Sided) 95% -1.56 to 1.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 4; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.86 | |
| Confidence Interval |
(2-Sided) 95% 0.57 to 3.14 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.399 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.60 | |
| Confidence Interval |
(2-Sided) 95% -0.80 to 2.01 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 2.52 | |
| Confidence Interval |
(2-Sided) 95% 1.12 to 3.92 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.71 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.668 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.30 | |
| Confidence Interval |
(2-Sided) 95% -1.08 to 1.68 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.76 | |
| Confidence Interval |
(2-Sided) 95% 0.39 to 3.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 36; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group x visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.109 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.20 | |
| Confidence Interval |
(2-Sided) 95% -0.27 to 2.67 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.75 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 36; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.163 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% -0.42 to 2.48 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 48; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.424 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.58 | |
| Confidence Interval |
(2-Sided) 95% -2.02 to 0.85 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 48; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.635 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.34 | |
| Confidence Interval |
(2-Sided) 95% -1.07 to 1.76 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 60; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.855 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.14 | |
| Confidence Interval |
(2-Sided) 95% -1.34 to 1.61 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.75 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 60; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.013 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.84 | |
| Confidence Interval |
(2-Sided) 95% 0.38 to 3.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 72; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.292 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.85 | |
| Confidence Interval |
(2-Sided) 95% -2.44 to 0.73 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.81 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 72; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.897 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% -1.47 to 1.68 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.80 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 84; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.390 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.72 | |
| Confidence Interval |
(2-Sided) 95% -2.36 to 0.92 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.84 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 84; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.659 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.37 | |
| Confidence Interval |
(2-Sided) 95% -1.26 to 1.99 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 96; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.847 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 95% -1.73 to 1.42 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.80 |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 96; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.333 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 95% -0.79 to 2.34 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.80 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Diastolic Blood Pressure (DBP) at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96 |
|---|---|
| Description | BP was measured by sphygmomanometer while participant was in supine position. Conditions were kept constant from visit to visit including observer, participant's same arm, cuff size, supine position, location, temperature, noise level. The same size BP cuff which was properly sized and calibrated, was used to measure BP each time. |
| Time Frame | Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants in the FAS who received at least 1 dose of the study medication. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 482 | 485 | 485 |
| Baseline (n =482, 485, 485) |
76.46
(7.68)
|
77.06
(7.53)
|
76.85
(7.71)
|
| Change at Week 2 (n =459, 466, 462) |
0.13
(6.63)
|
0.58
(6.61)
|
0.37
(7.07)
|
| Change at Week 4 (n =467, 467, 465) |
0.07
(7.04)
|
0.78
(7.33)
|
-0.41
(7.11)
|
| Change at Week 12 (n =450, 455, 461) |
0.02
(7.29)
|
1.21
(7.56)
|
0.05
(7.58)
|
| Change at Week 24 (n =425, 432, 439) |
0.02
(7.46)
|
0.53
(7.80)
|
-0.33
(7.52)
|
| Change at Week 36 (n =385, 415, 418) |
-0.21
(7.86)
|
-0.31
(7.58)
|
-1.18
(7.86)
|
| Change at Week 48 (n =377, 400, 410) |
-0.16
(8.28)
|
-0.19
(7.99)
|
-0.07
(7.67)
|
| Change at Week 60 (n =360, 377, 384) |
-0.69
(7.56)
|
0.10
(7.91)
|
-0.84
(8.32)
|
| Change at Week 72 (n =357, 374, 370) |
-0.49
(8.06)
|
0.30
(8.81)
|
-0.77
(8.14)
|
| Change at Week 84 (n= 346, 366, 362) |
-0.39
(8.03)
|
-0.28
(7.93)
|
-0.78
(8.60)
|
| Change at Week 96 (n =344, 353, 356) |
-0.21
(8.02)
|
-0.20
(8.82)
|
-0.70
(8.47)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 2; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.238 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.49 | |
| Confidence Interval |
(2-Sided) 95% -1.31 to 0.32 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.42 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 2; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.815 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.10 | |
| Confidence Interval |
(2-Sided) 95% -0.72 to 0.91 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.41 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 4; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.508 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.54 to 1.10 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.42 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 4; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.20 | |
| Confidence Interval |
(2-Sided) 95% 0.38 to 2.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.42 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.683 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.18 | |
| Confidence Interval |
(2-Sided) 95% -1.07 to 0.70 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.45 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.21 | |
| Confidence Interval |
(2-Sided) 95% 0.33 to 2.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.45 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.687 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.18 | |
| Confidence Interval |
(2-Sided) 95% -0.71 to 1.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.45 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.050 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% -0.00 to 1.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.45 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 36; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.215 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.60 | |
| Confidence Interval |
(2-Sided) 95% -0.35 to 1.54 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.48 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 36; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.042 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.96 | |
| Confidence Interval |
(2-Sided) 95% 0.03 to 1.89 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.47 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 48; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.401 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.42 | |
| Confidence Interval |
(2-Sided) 95% -1.41 to 0.56 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 48; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.980 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 95% -0.96 to 0.99 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 60; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.632 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.24 | |
| Confidence Interval |
(2-Sided) 95% -1.25 to 0.76 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 60; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.032 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.08 | |
| Confidence Interval |
(2-Sided) 95% 0.09 to 2.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 72; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.668 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.23 | |
| Confidence Interval |
(2-Sided) 95% -1.29 to 0.83 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 72; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 95% 0.06 to 2.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 84; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.868 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -1.13 to 0.95 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 84; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.257 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.59 | |
| Confidence Interval |
(2-Sided) 95% -0.43 to 1.62 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 96; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.895 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.07 | |
| Confidence Interval |
(2-Sided) 95% -1.00 to 1.15 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.55 |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 96; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.268 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.60 | |
| Confidence Interval |
(2-Sided) 95% -0.46 to 1.67 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Heart Rate at Week 2, 4, 12, 24, 36, 48, 60, 72, 84 and 96 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 2, 4, 12, 24, 36, 48, 60, 72, 84, 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants in the FAS who received at least 1 dose of the study medication. Here, 'n' signifies participants evaluable for this outcome measure at given time points for each group. |
| Arm/Group Title | SD-0610 50 Milligram (mg) | SD-0610 200 mg | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. |
| Measure Participants | 482 | 485 | 485 |
| Baseline (n =482, 485, 485) |
69.74
(9.11)
|
69.12
(8.72)
|
69.34
(8.26)
|
| Change at Week 2 (n =459, 466, 461) |
0.58
(7.35)
|
-0.29
(6.68)
|
0.71
(7.55)
|
| Change at Week 4 (n =467, 466, 465) |
0.24
(7.53)
|
0.23
(7.46)
|
0.78
(7.77)
|
| Change at Week 12 (n =450, 455, 461) |
0.13
(7.70)
|
-0.17
(7.61)
|
0.05
(8.24)
|
| Change at Week 24 (n =425, 432, 439) |
0.45
(8.30)
|
-0.42
(7.46)
|
0.06
(8.37)
|
| Change at Week 36 (n =384, 415, 418) |
-0.08
(8.58)
|
-0.07
(7.80)
|
0.76
(8.41)
|
| Change at Week 48 (n =377, 399, 410) |
-0.82
(8.45)
|
-1.37
(8.23)
|
-0.11
(8.59)
|
| Change at Week 60 (n =360, 377, 384) |
-0.42
(8.37)
|
0.04
(7.56)
|
0.47
(8.90)
|
| Change at Week 72 (n =357, 374, 370) |
-0.95
(8.75)
|
-0.99
(7.91)
|
0.85
(9.56)
|
| Change at Week 84 (n =346, 366, 362) |
-0.31
(8.65)
|
-0.15
(7.88)
|
0.57
(8.64)
|
| Change at Week 96 (n =344, 353, 356) |
-1.09
(8.91)
|
-0.61
(8.53)
|
0.36
(8.61)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 2; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.908 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.92 to 0.82 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.44 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 2; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.18 | |
| Confidence Interval |
(2-Sided) 95% -2.05 to -0.31 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.44 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 4; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.440 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.35 | |
| Confidence Interval |
(2-Sided) 95% -1.25 to 0.54 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.46 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 4; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.140 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.67 | |
| Confidence Interval |
(2-Sided) 95% -1.57 to 0.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.46 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.474 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.33 | |
| Confidence Interval |
(2-Sided) 95% -0.58 to 1.24 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.46 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 12; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.376 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.41 | |
| Confidence Interval |
(2-Sided) 95% -1.32 to 0.50 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.46 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.186 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | 0.66 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 1.64 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 24; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.185 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.66 | |
| Confidence Interval |
(2-Sided) 95% -1.63 to 0.32 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 36; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.334 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.51 | |
| Confidence Interval |
(2-Sided) 95% -1.53 to 0.52 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 36; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.055 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.99 | |
| Confidence Interval |
(2-Sided) 95% -2.00 to 0.02 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 48; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.539 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.33 | |
| Confidence Interval |
(2-Sided) 95% -1.38 to 0.72 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 48; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.018 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.26 | |
| Confidence Interval |
(2-Sided) 95% -2.30 to -0.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 60; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.365 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.48 | |
| Confidence Interval |
(2-Sided) 95% -1.52 to 0.56 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 60; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.403 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.44 | |
| Confidence Interval |
(2-Sided) 95% -1.47 to 0.59 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 72; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.020 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.32 | |
| Confidence Interval |
(2-Sided) 95% -2.43 to -0.21 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 72; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.87 | |
| Confidence Interval |
(2-Sided) 95% -2.98 to -0.77 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 84; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.269 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.60 | |
| Confidence Interval |
(2-Sided) 95% -1.66 to 0.46 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 84; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.104 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -0.87 | |
| Confidence Interval |
(2-Sided) 95% -1.92 to 0.18 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 50 Milligram (mg), Placebo |
|---|---|---|
| Comments | Week 96; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.18 | |
| Confidence Interval |
(2-Sided) 95% -2.30 to -0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | SD-0610 200 mg, Placebo |
|---|---|---|
| Comments | Week 96; LS-Mean, 95 percent CI and P-values were obtained from a discrete time MMRM model with fixed effects for treatment group, visit, a treatment group*visit interaction, (collapsed) KLG, a (collapsed) KLG*visit interaction, baseline value, geographic region, gender, age and body mass index with an unstructured covariance matrix. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.041 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -1.16 | |
| Confidence Interval |
(2-Sided) 95% -2.28 to -0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Baseline up to Week 111 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. | |||||
| Arm/Group Title | SD-6010 50 Milligram (mg) | SD-6010 200 mg | Placebo | |||
| Arm/Group Description | Participants with symptomatic osteoarthritis (OA) of knee, received 50 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received 200 mg tablet of SD-6010 orally, once daily for 24 months. | Participants with symptomatic OA of knee, received placebo matched to SD-6010 orally, once daily for 24 months. | |||
All Cause Mortality |
||||||
| SD-6010 50 Milligram (mg) | SD-6010 200 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| SD-6010 50 Milligram (mg) | SD-6010 200 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 43/482 (8.9%) | 61/485 (12.6%) | 49/485 (10.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Coagulopathy | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Thrombocytopenia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Angina unstable | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Arrhythmia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Atrial fibrillation | 1/482 (0.2%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Bradyarrhythmia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Bradycardia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cardiac arrest | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cardiac disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Cardiac failure | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Cardiac failure chronic | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cardiac failure congestive | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Coronary artery disease | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Coronary artery occlusion | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Coronary artery stenosis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Myocardial infarction | 0/482 (0%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Prinzmetal angina | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ventricular tachycardia | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal hernia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Colonic polyp | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Constipation | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Diverticulum | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Duodenal ulcer | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Gastric disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Gastric ulcer | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Gastritis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Gastritis erosive | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Gastrointestinal haemorrhage | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Gastrooesophageal reflux disease | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hernial eventration | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hiatus hernia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Internal hernia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Pancreatitis acute | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Small intestinal obstruction | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Umbilical hernia | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Vomiting | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| General disorders | ||||||
| Chest pain | 4/482 (0.8%) | 3/485 (0.6%) | 2/485 (0.4%) | |||
| Device dislocation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Fatigue | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Medical device complication | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Non-cardiac chest pain | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pyrexia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Cholelithiasis | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Gallbladder polyp | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Infections and infestations | ||||||
| Abdominal abscess | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Abdominal wall abscess | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Abscess limb | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Appendicitis | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Clostridium difficile colitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Diverticulitis | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Enterocolitis infectious | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Gastric ulcer helicobacter | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gastroenteritis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Helicobacter infection | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Infectious peritonitis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Meningitis bacterial | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Osteomyelitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pneumonia | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Pseudomembranous colitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pyelonephritis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Sepsis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Septic shock | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Tonsillitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Urinary tract infection | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Viral infection | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Wound infection | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Injury, poisoning and procedural complications | ||||||
| Anastomotic ulcer | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Ankle fracture | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Arthropod bite | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Clavicle fracture | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Comminuted fracture | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Concussion | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Contusion | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Craniocerebral injury | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Deep vein thrombosis postoperative | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Fall | 2/482 (0.4%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Femoral neck fracture | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Femur fracture | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Laceration | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ligament injury | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Limb injury | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Meniscus lesion | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Operative haemorrhage | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Radius fracture | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Rib fracture | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Skull fracture | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Splenic rupture | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Tendon rupture | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Ulna fracture | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Investigations | ||||||
| Blood pressure increased | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Borrelia test positive | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Diabetic ketoacidosis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/482 (0.4%) | 3/485 (0.6%) | 2/485 (0.4%) | |||
| Intervertebral disc protrusion | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Limb discomfort | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Musculoskeletal chest pain | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Osteoarthritis | 6/482 (1.2%) | 1/485 (0.2%) | 7/485 (1.4%) | |||
| Osteonecrosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rhabdomyolysis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Spinal column stenosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Systemic lupus erythematosus | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Adenocarcinoma | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Basal cell carcinoma | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Breast cancer | 1/482 (0.2%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Chronic lymphocytic leukaemia | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Endometrial cancer | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Lung neoplasm malignant | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Malignant melanoma | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Malignant melanoma in situ | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Nasal cavity cancer | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Neoplasm malignant | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Ovarian cancer stage III | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Prostate cancer recurrent | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Squamous cell carcinoma | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Thyroid cancer | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Uterine cancer | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Uterine leiomyoma | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Nervous system disorders | ||||||
| Cerebral haemorrhage | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Facial paresis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Haemorrhagic stroke | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Lacunar infarction | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Loss of consciousness | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Orthostatic intolerance | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Presyncope | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Sciatica | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Spinal cord compression | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Spinal vascular disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Subarachnoid haemorrhage | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Transient ischaemic attack | 1/482 (0.2%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Tremor | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Psychiatric disorders | ||||||
| Depression | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Mental status changes | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Suicide attempt | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Renal and urinary disorders | ||||||
| Bladder perforation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Haematuria | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Renal failure | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Urinary incontinence | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Urinary retention | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Urogenital disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Cystocele | 0/482 (0%) | 3/485 (0.6%) | 0/485 (0%) | |||
| Endometrial disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Metrorrhagia | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Uterine haemorrhage | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Uterine prolapse | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Dyspnoea | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Lung disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hypertension | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Hypertensive crisis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| SD-6010 50 Milligram (mg) | SD-6010 200 mg | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 365/482 (75.7%) | 371/485 (76.5%) | 360/485 (74.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/482 (0.4%) | 2/485 (0.4%) | 9/485 (1.9%) | |||
| Eosinophilia | 1/482 (0.2%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Hypochromasia | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Hypochromic anaemia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Iron deficiency anaemia | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Leukocytosis | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Lymphadenopathy | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Lymphocytosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Neutropenia | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Thrombocytopenia | 0/482 (0%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Thrombocytosis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Aortic valve incompetence | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Arrhythmia supraventricular | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Atrial fibrillation | 1/482 (0.2%) | 0/485 (0%) | 4/485 (0.8%) | |||
| Atrial flutter | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Atrioventricular block first degree | 2/482 (0.4%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Bradycardia | 0/482 (0%) | 3/485 (0.6%) | 0/485 (0%) | |||
| Bundle branch block left | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Bundle branch block right | 0/482 (0%) | 0/485 (0%) | 3/485 (0.6%) | |||
| Cardiac failure | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cardiac flutter | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Cardiomegaly | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Extrasystoles | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Mitral valve incompetence | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Palpitations | 3/482 (0.6%) | 7/485 (1.4%) | 3/485 (0.6%) | |||
| Pericardial effusion | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Sick sinus syndrome | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Sinus arrhythmia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Sinus bradycardia | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Supraventricular extrasystoles | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Supraventricular tachycardia | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Tachycardia | 2/482 (0.4%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Tricuspid valve incompetence | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ventricular extrasystoles | 2/482 (0.4%) | 1/485 (0.2%) | 4/485 (0.8%) | |||
| Congenital, familial and genetic disorders | ||||||
| Brain malformation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Vascular anomaly | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Cerumen impaction | 3/482 (0.6%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Ear disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Ear pain | 1/482 (0.2%) | 4/485 (0.8%) | 1/485 (0.2%) | |||
| Ear pruritus | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hypoacusis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Inner ear inflammation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Tinnitus | 3/482 (0.6%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Tympanic membrane perforation | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Vertigo | 7/482 (1.5%) | 4/485 (0.8%) | 7/485 (1.4%) | |||
| Vertigo positional | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Endocrine disorders | ||||||
| Goitre | 4/482 (0.8%) | 1/485 (0.2%) | 4/485 (0.8%) | |||
| Hypogonadism | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Hypoparathyroidism | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Thyroid cyst | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Thyroiditis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hypothyroidism | 6/482 (1.2%) | 3/485 (0.6%) | 3/485 (0.6%) | |||
| Eye disorders | ||||||
| Abnormal sensation in eye | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Age-related macular degeneration | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Arcus lipoides | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Blepharitis | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cataract | 5/482 (1%) | 7/485 (1.4%) | 2/485 (0.4%) | |||
| Cataract subcapsular | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Conjunctival haemorrhage | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Conjunctivitis | 2/482 (0.4%) | 4/485 (0.8%) | 1/485 (0.2%) | |||
| Dry eye | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Erythema of eyelid | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Eye allergy | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Eye inflammation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Eye pain | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Eye pruritus | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Eyelid irritation | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Eyelid ptosis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Glaucoma | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Maculopathy | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Ocular hyperaemia | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Ocular hypertension | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Papilloedema | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Retinal detachment | 3/482 (0.6%) | 0/485 (0%) | 0/485 (0%) | |||
| Retinal disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Retinal haemorrhage | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Vision blurred | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Visual acuity reduced | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 5/482 (1%) | 4/485 (0.8%) | 8/485 (1.6%) | |||
| Abdominal distension | 1/482 (0.2%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Abdominal pain | 8/482 (1.7%) | 11/485 (2.3%) | 14/485 (2.9%) | |||
| Abdominal pain lower | 2/482 (0.4%) | 4/485 (0.8%) | 2/485 (0.4%) | |||
| Abdominal pain upper | 9/482 (1.9%) | 13/485 (2.7%) | 12/485 (2.5%) | |||
| Abdominal tenderness | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Anal polyp | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Breath odour | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Change of bowel habit | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Cheilitis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Colitis | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Colitis microscopic | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Colitis ulcerative | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Colonic polyp | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Constipation | 8/482 (1.7%) | 9/485 (1.9%) | 8/485 (1.6%) | |||
| Dental caries | 3/482 (0.6%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Diarrhoea | 22/482 (4.6%) | 27/485 (5.6%) | 29/485 (6%) | |||
| Diverticulum | 2/482 (0.4%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Diverticulum intestinal | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Dry mouth | 5/482 (1%) | 0/485 (0%) | 6/485 (1.2%) | |||
| Dyspepsia | 10/482 (2.1%) | 14/485 (2.9%) | 14/485 (2.9%) | |||
| Dysphagia | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Enteritis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Eructation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Femoral hernia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Flatulence | 5/482 (1%) | 2/485 (0.4%) | 4/485 (0.8%) | |||
| Food poisoning | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Frequent bowel movements | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Gastric disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gastric polyps | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gastric ulcer | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Gastritis | 4/482 (0.8%) | 11/485 (2.3%) | 4/485 (0.8%) | |||
| Gastritis erosive | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Gastrointestinal haemorrhage | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gastrooesophageal reflux disease | 10/482 (2.1%) | 12/485 (2.5%) | 9/485 (1.9%) | |||
| Gingival bleeding | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gingival disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gingival recession | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Gingivitis | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Haematemesis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Haematochezia | 1/482 (0.2%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Haemorrhoidal haemorrhage | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Haemorrhoids | 6/482 (1.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hiatus hernia | 1/482 (0.2%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Hyperchlorhydria | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Irritable bowel syndrome | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Lip swelling | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Mouth ulceration | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Nausea | 20/482 (4.1%) | 15/485 (3.1%) | 14/485 (2.9%) | |||
| Oesophageal disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Oesophageal stenosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Oesophagitis | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Omental infarction | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Oral disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pancreatic cyst | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Pancreatic disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Pancreatitis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Pancreatitis acute | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Pancreatitis chronic | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Paraesthesia oral | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Peptic ulcer | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Periodontitis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Rectal haemorrhage | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rectal polyp | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Steatorrhoea | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Stomatitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Swollen tongue | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Tooth impacted | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Toothache | 5/482 (1%) | 2/485 (0.4%) | 8/485 (1.6%) | |||
| Umbilical hernia | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Vomiting | 9/482 (1.9%) | 12/485 (2.5%) | 3/485 (0.6%) | |||
| General disorders | ||||||
| Application site dermatitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Asthenia | 3/482 (0.6%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Chest discomfort | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Chest pain | 6/482 (1.2%) | 8/485 (1.6%) | 8/485 (1.6%) | |||
| Chills | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cyst | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Facial pain | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Fatigue | 10/482 (2.1%) | 12/485 (2.5%) | 13/485 (2.7%) | |||
| Feeling cold | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gait disturbance | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Inflammation | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Influenza like illness | 2/482 (0.4%) | 6/485 (1.2%) | 1/485 (0.2%) | |||
| Injection site erythema | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Injection site inflammation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Injection site pruritus | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Irritability | 4/482 (0.8%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Malaise | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Medical device pain | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Medical device site reaction | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Non-cardiac chest pain | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Oedema | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Oedema peripheral | 15/482 (3.1%) | 15/485 (3.1%) | 19/485 (3.9%) | |||
| Pain | 4/482 (0.8%) | 6/485 (1.2%) | 2/485 (0.4%) | |||
| Polyp | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Pyrexia | 1/482 (0.2%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Soft tissue inflammation | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Tenderness | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Thirst | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Ulcer | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Ulcer haemorrhage | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Hepatobiliary disorders | ||||||
| Biliary colic | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Biliary tract disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Cholecystitis chronic | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cholelithiasis | 3/482 (0.6%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Gallbladder polyp | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Hepatic function abnormal | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hepatic steatosis | 2/482 (0.4%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Hydrocholecystis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Liver disorder | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Immune system disorders | ||||||
| Allergy to arthropod sting | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Drug hypersensitivity | 2/482 (0.4%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Food allergy | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hypersensitivity | 0/482 (0%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Sarcoidosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Seasonal allergy | 3/482 (0.6%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Infections and infestations | ||||||
| Abscess | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Abscess limb | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Acariasis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Acute sinusitis | 5/482 (1%) | 6/485 (1.2%) | 5/485 (1%) | |||
| Appendicitis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Arthritis infective | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Beta haemolytic streptococcal infection | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Body tinea | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Borrelia infection | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Bronchitis | 25/482 (5.2%) | 30/485 (6.2%) | 20/485 (4.1%) | |||
| Bronchitis viral | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Candidiasis | 3/482 (0.6%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Carbuncle | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Cellulitis | 3/482 (0.6%) | 8/485 (1.6%) | 6/485 (1.2%) | |||
| Cystitis | 3/482 (0.6%) | 6/485 (1.2%) | 3/485 (0.6%) | |||
| Device related infection | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Diarrhoea infectious | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Diverticulitis | 2/482 (0.4%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Ear infection | 8/482 (1.7%) | 8/485 (1.6%) | 2/485 (0.4%) | |||
| Erysipelas | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Erythema migrans | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Escherichia urinary tract infection | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Eye infection | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Folliculitis | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Fungal infection | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Fungal skin infection | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Gastroenteritis | 9/482 (1.9%) | 9/485 (1.9%) | 4/485 (0.8%) | |||
| Gastroenteritis viral | 5/482 (1%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Gastrointestinal infection | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Gastrointestinal viral infection | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Genital infection fungal | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Giardiasis | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Gingival infection | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Helicobacter infection | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Herpes ophthalmic | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Herpes simplex | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Herpes virus infection | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Herpes zoster | 9/482 (1.9%) | 5/485 (1%) | 5/485 (1%) | |||
| Hordeolum | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Impetigo | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Infected cyst | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Infection parasitic | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Influenza | 13/482 (2.7%) | 12/485 (2.5%) | 14/485 (2.9%) | |||
| Labyrinthitis | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Laryngitis | 0/482 (0%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Laryngitis viral | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Localised infection | 0/482 (0%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Lower respiratory tract infection | 1/482 (0.2%) | 0/485 (0%) | 3/485 (0.6%) | |||
| Lyme disease | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Mastitis bacterial | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Nasopharyngitis | 33/482 (6.8%) | 41/485 (8.5%) | 25/485 (5.2%) | |||
| Onychomycosis | 3/482 (0.6%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Oral candidiasis | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Oral herpes | 2/482 (0.4%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Osteomyelitis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Otitis externa | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Otitis media | 2/482 (0.4%) | 0/485 (0%) | 3/485 (0.6%) | |||
| Otitis media acute | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Paronychia | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Pharyngitis | 7/482 (1.5%) | 16/485 (3.3%) | 7/485 (1.4%) | |||
| Pharyngitis bacterial | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pharyngitis streptococcal | 4/482 (0.8%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Pharyngotonsillitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pilonidal cyst | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Pneumonia | 4/482 (0.8%) | 6/485 (1.2%) | 4/485 (0.8%) | |||
| Post procedural infection | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Postoperative wound infection | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pyelonephritis | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Renal abscess | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Respiratory tract infection | 1/482 (0.2%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Respiratory tract infection viral | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rhinitis | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Sinusitis | 18/482 (3.7%) | 18/485 (3.7%) | 14/485 (2.9%) | |||
| Skin infection | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Staphylococcal infection | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Subcutaneous abscess | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Tinea pedis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Tonsillitis | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Tooth abscess | 6/482 (1.2%) | 4/485 (0.8%) | 2/485 (0.4%) | |||
| Tracheitis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Typhus | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Upper respiratory tract infection | 40/482 (8.3%) | 31/485 (6.4%) | 30/485 (6.2%) | |||
| Upper respiratory tract infection bacterial | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Urinary tract infection | 24/482 (5%) | 21/485 (4.3%) | 26/485 (5.4%) | |||
| Vaginal infection | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Viral infection | 2/482 (0.4%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Viral pharyngitis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Viral tonsillitis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Viral upper respiratory tract infection | 1/482 (0.2%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Vulvovaginal mycotic infection | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Vulvovaginitis | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Wound infection | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Tooth infection | 4/482 (0.8%) | 4/485 (0.8%) | 2/485 (0.4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Animal bite | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Ankle fracture | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Arthropod bite | 0/482 (0%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Back injury | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Bone fragmentation | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Burns first degree | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Burns second degree | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Chest injury | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Clavicle fracture | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Concussion | 0/482 (0%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Contusion | 12/482 (2.5%) | 12/485 (2.5%) | 10/485 (2.1%) | |||
| Corneal abrasion | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Craniocerebral injury | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Epicondylitis | 2/482 (0.4%) | 3/485 (0.6%) | 3/485 (0.6%) | |||
| Eschar | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Excoriation | 4/482 (0.8%) | 4/485 (0.8%) | 5/485 (1%) | |||
| Fall | 26/482 (5.4%) | 41/485 (8.5%) | 28/485 (5.8%) | |||
| Fibula fracture | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Foot fracture | 1/482 (0.2%) | 4/485 (0.8%) | 2/485 (0.4%) | |||
| Forearm fracture | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Foreign body in eye | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Fracture | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hand fracture | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Head injury | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Heat exhaustion | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Joint dislocation | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Joint injury | 2/482 (0.4%) | 4/485 (0.8%) | 1/485 (0.2%) | |||
| Laceration | 3/482 (0.6%) | 4/485 (0.8%) | 2/485 (0.4%) | |||
| Ligament injury | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Ligament rupture | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ligament sprain | 8/482 (1.7%) | 11/485 (2.3%) | 7/485 (1.4%) | |||
| Limb injury | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Meniscus lesion | 6/482 (1.2%) | 6/485 (1.2%) | 9/485 (1.9%) | |||
| Muscle rupture | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Muscle strain | 8/482 (1.7%) | 5/485 (1%) | 6/485 (1.2%) | |||
| Periorbital haematoma | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Periorbital haemorrhage | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Post procedural complication | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Post-traumatic neck syndrome | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Procedural pain | 1/482 (0.2%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Radius fracture | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Rib fracture | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Road traffic accident | 2/482 (0.4%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Scratch | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Skeletal injury | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Soft tissue injury | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Stab wound | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Stress fracture | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Tendon injury | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Tendon rupture | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Thermal burn | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Tooth fracture | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Traumatic haematoma | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Ulna fracture | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Upper limb fracture | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Wound | 0/482 (0%) | 0/485 (0%) | 3/485 (0.6%) | |||
| Wrist fracture | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 1/482 (0.2%) | 5/485 (1%) | 2/485 (0.4%) | |||
| Aspartate aminotransferase increased | 3/482 (0.6%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Blood alkaline phosphatase increased | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Blood amylase increased | 3/482 (0.6%) | 6/485 (1.2%) | 3/485 (0.6%) | |||
| Blood bicarbonate decreased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Blood bilirubin increased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Blood calcium increased | 3/482 (0.6%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Blood cholesterol abnormal | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Blood cholesterol increased | 0/482 (0%) | 3/485 (0.6%) | 2/485 (0.4%) | |||
| Blood creatine increased | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Blood creatinine increased | 2/482 (0.4%) | 3/485 (0.6%) | 4/485 (0.8%) | |||
| Blood glucose increased | 2/482 (0.4%) | 3/485 (0.6%) | 3/485 (0.6%) | |||
| Blood potassium decreased | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Blood pressure decreased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Blood pressure increased | 13/482 (2.7%) | 24/485 (4.9%) | 21/485 (4.3%) | |||
| Blood testosterone decreased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Blood thyroid stimulating hormone increased | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Blood triglycerides increased | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Blood urea increased | 4/482 (0.8%) | 0/485 (0%) | 0/485 (0%) | |||
| Blood uric acid increased | 2/482 (0.4%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Blood urine present | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Body temperature increased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Cardiac murmur | 3/482 (0.6%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ceruloplasmin increased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| ECG signs of myocardial ischaemia | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Electrocardiogram T wave abnormal | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Eosinophil count increased | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Femoral bruit | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Gamma-glutamyltransferase increased | 0/482 (0%) | 10/485 (2.1%) | 4/485 (0.8%) | |||
| Haematocrit decreased | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Haematology test abnormal | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Haemoglobin decreased | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Heart rate increased | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Heart rate irregular | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Helicobacter test positive | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hepatic enzyme abnormal | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Hepatic enzyme increased | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Lipase increased | 7/482 (1.5%) | 8/485 (1.6%) | 7/485 (1.4%) | |||
| Liver function test abnormal | 3/482 (0.6%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Low density lipoprotein increased | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Monocyte count decreased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Neutrophil count decreased | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Neutrophil count increased | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Pancreatic enzymes increased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Prostatic specific antigen increased | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Protein urine present | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Red blood cell burr cells present | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Serum ferritin increased | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Tandem gait test abnormal | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Transaminases increased | 0/482 (0%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Ultrasound kidney abnormal | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Vitamin B12 decreased | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Vitamin D decreased | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Waist circumference increased | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Weight decreased | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Weight increased | 1/482 (0.2%) | 7/485 (1.4%) | 5/485 (1%) | |||
| White blood cell count abnormal | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| White blood cell count decreased | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Cholesterosis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Decreased appetite | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Dehydration | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Diabetes mellitus | 3/482 (0.6%) | 4/485 (0.8%) | 4/485 (0.8%) | |||
| Diabetes mellitus inadequate control | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Dyslipidaemia | 0/482 (0%) | 3/485 (0.6%) | 5/485 (1%) | |||
| Fluid retention | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Glucose tolerance impaired | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Gout | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hypercalcaemia | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Hypercholesterolaemia | 9/482 (1.9%) | 3/485 (0.6%) | 4/485 (0.8%) | |||
| Hyperglycaemia | 0/482 (0%) | 3/485 (0.6%) | 0/485 (0%) | |||
| Hyperkalaemia | 1/482 (0.2%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Hyperlipidaemia | 2/482 (0.4%) | 1/485 (0.2%) | 4/485 (0.8%) | |||
| Hypertriglyceridaemia | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Hyperuricaemia | 3/482 (0.6%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hypocalcaemia | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hypoglycaemia | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hypokalaemia | 1/482 (0.2%) | 6/485 (1.2%) | 0/485 (0%) | |||
| Hypomagnesaemia | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hyponatraemia | 2/482 (0.4%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Increased appetite | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Iron deficiency | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Lactose intolerance | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Obesity | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Type 2 diabetes mellitus | 4/482 (0.8%) | 2/485 (0.4%) | 5/485 (1%) | |||
| Vitamin B12 deficiency | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Vitamin D deficiency | 1/482 (0.2%) | 3/485 (0.6%) | 0/485 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 69/482 (14.3%) | 65/485 (13.4%) | 65/485 (13.4%) | |||
| Arthritis | 1/482 (0.2%) | 8/485 (1.6%) | 4/485 (0.8%) | |||
| Arthrofibrosis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Arthropathy | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Articular calcification | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Back pain | 31/482 (6.4%) | 32/485 (6.6%) | 43/485 (8.9%) | |||
| Bone loss | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Bone pain | 2/482 (0.4%) | 2/485 (0.4%) | 3/485 (0.6%) | |||
| Bone swelling | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Bunion | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Bursitis | 12/482 (2.5%) | 2/485 (0.4%) | 7/485 (1.4%) | |||
| Chondrocalcinosis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Chondrocalcinosis pyrophosphate | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Chondromalacia | 0/482 (0%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Chondropathy | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Connective tissue disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Connective tissue inflammation | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Exostosis | 4/482 (0.8%) | 2/485 (0.4%) | 2/485 (0.4%) | |||
| Facet joint syndrome | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Fasciitis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Fibromyalgia | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Flank pain | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Foot deformity | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Groin pain | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Haemarthrosis | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Intervertebral disc compression | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Intervertebral disc degeneration | 1/482 (0.2%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Intervertebral disc protrusion | 2/482 (0.4%) | 3/485 (0.6%) | 3/485 (0.6%) | |||
| Joint crepitation | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Joint effusion | 1/482 (0.2%) | 3/485 (0.6%) | 5/485 (1%) | |||
| Joint instability | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Joint lock | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Joint range of motion decreased | 5/482 (1%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Joint stiffness | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Joint swelling | 14/482 (2.9%) | 8/485 (1.6%) | 7/485 (1.4%) | |||
| Joint warmth | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Lordosis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Lumbar spinal stenosis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Meniscal degeneration | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Metatarsalgia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Muscle contracture | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Muscle disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Muscle spasms | 12/482 (2.5%) | 9/485 (1.9%) | 3/485 (0.6%) | |||
| Muscle twitching | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Muscular weakness | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Musculoskeletal chest pain | 1/482 (0.2%) | 5/485 (1%) | 1/485 (0.2%) | |||
| Musculoskeletal discomfort | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Musculoskeletal pain | 12/482 (2.5%) | 13/485 (2.7%) | 17/485 (3.5%) | |||
| Musculoskeletal stiffness | 2/482 (0.4%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Myalgia | 5/482 (1%) | 6/485 (1.2%) | 5/485 (1%) | |||
| Myofascial pain syndrome | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Neck mass | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Neck pain | 6/482 (1.2%) | 12/485 (2.5%) | 7/485 (1.4%) | |||
| Nodal osteoarthritis | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Osteitis | 0/482 (0%) | 0/485 (0%) | 4/485 (0.8%) | |||
| Osteoarthritis | 21/482 (4.4%) | 23/485 (4.7%) | 14/485 (2.9%) | |||
| Osteonecrosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Osteopenia | 2/482 (0.4%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Osteoporosis | 2/482 (0.4%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Pain in extremity | 13/482 (2.7%) | 19/485 (3.9%) | 21/485 (4.3%) | |||
| Pain in jaw | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Periarthritis | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Plantar fasciitis | 6/482 (1.2%) | 3/485 (0.6%) | 9/485 (1.9%) | |||
| Polyarthritis | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Polymyalgia rheumatica | 0/482 (0%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Resorption bone increased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rotator cuff syndrome | 2/482 (0.4%) | 6/485 (1.2%) | 5/485 (1%) | |||
| Sjogren's syndrome | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Soft tissue mass | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Spinal column stenosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Spinal disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Spinal osteoarthritis | 6/482 (1.2%) | 3/485 (0.6%) | 3/485 (0.6%) | |||
| Spondylitis | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Spondylolysis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Synovial cyst | 3/482 (0.6%) | 2/485 (0.4%) | 4/485 (0.8%) | |||
| Synovitis | 0/482 (0%) | 0/485 (0%) | 3/485 (0.6%) | |||
| Tendon disorder | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Tendonitis | 9/482 (1.9%) | 14/485 (2.9%) | 11/485 (2.3%) | |||
| Tenosynovitis stenosans | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Trigger finger | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Acrochordon | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Basal cell carcinoma | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Benign breast neoplasm | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Benign neoplasm of skin | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Breast cancer | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Lip neoplasm malignant stage unspecified | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Lipoma | 2/482 (0.4%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Lung neoplasm | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Melanocytic naevus | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Morton's neuroma | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Myelodysplastic syndrome | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Neoplasm of appendix | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Neuroma | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ovarian adenoma | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Paranasal sinus benign neoplasm | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Seborrhoeic keratosis | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Squamous cell carcinoma | 3/482 (0.6%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Squamous cell carcinoma of skin | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Thyroid neoplasm | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Uterine leiomyoma | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Nervous system disorders | ||||||
| Amnesia | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Balance disorder | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Burning sensation | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Carotid artery disease | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Carotid artery stenosis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Carpal tunnel syndrome | 3/482 (0.6%) | 2/485 (0.4%) | 6/485 (1.2%) | |||
| Cerebral microangiopathy | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Cervicobrachial syndrome | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Cluster headache | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Cognitive disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Decreased vibratory sense | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Diabetic neuropathy | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Disturbance in attention | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Dizziness | 17/482 (3.5%) | 22/485 (4.5%) | 11/485 (2.3%) | |||
| Dysgeusia | 3/482 (0.6%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Headache | 32/482 (6.6%) | 27/485 (5.6%) | 18/485 (3.7%) | |||
| Hemiparesis | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Hypertonia | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hypoaesthesia | 4/482 (0.8%) | 5/485 (1%) | 2/485 (0.4%) | |||
| Hyporeflexia | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Lethargy | 3/482 (0.6%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Loss of consciousness | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Lumbar radiculopathy | 2/482 (0.4%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Memory impairment | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Meralgia paraesthetica | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Migraine | 6/482 (1.2%) | 7/485 (1.4%) | 1/485 (0.2%) | |||
| Migraine with aura | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Multiple sclerosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Muscle contractions involuntary | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Nerve compression | 2/482 (0.4%) | 0/485 (0%) | 3/485 (0.6%) | |||
| Neuralgia | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Neuritis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Neuropathy peripheral | 2/482 (0.4%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Paraesthesia | 5/482 (1%) | 3/485 (0.6%) | 3/485 (0.6%) | |||
| Parkinson's disease | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Presyncope | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Radicular syndrome | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Radiculitis | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Radiculitis cervical | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Restless legs syndrome | 3/482 (0.6%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Sciatic nerve neuropathy | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Sciatica | 4/482 (0.8%) | 10/485 (2.1%) | 2/485 (0.4%) | |||
| Sinus headache | 1/482 (0.2%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Sleep phase rhythm disturbance | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Somnolence | 0/482 (0%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Syncope | 3/482 (0.6%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Tension headache | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Tremor | 2/482 (0.4%) | 2/485 (0.4%) | 0/485 (0%) | |||
| VIIth nerve paralysis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Vascular encephalopathy | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 6/482 (1.2%) | 7/485 (1.4%) | 5/485 (1%) | |||
| Confusional state | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Depressed mood | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Depression | 12/482 (2.5%) | 12/485 (2.5%) | 6/485 (1.2%) | |||
| Disorientation | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Emotional distress | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Euphoric mood | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Insomnia | 9/482 (1.9%) | 5/485 (1%) | 7/485 (1.4%) | |||
| Mood swings | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Nervousness | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Panic attack | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Sleep disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Substance abuse | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Renal and urinary disorders | ||||||
| Bladder disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Bladder spasm | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Calculus bladder | 0/482 (0%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Dysuria | 5/482 (1%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Haematuria | 5/482 (1%) | 2/485 (0.4%) | 6/485 (1.2%) | |||
| Haemorrhage urinary tract | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Hypertonic bladder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Incontinence | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Micturition urgency | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Nephrolithiasis | 2/482 (0.4%) | 4/485 (0.8%) | 3/485 (0.6%) | |||
| Nocturia | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pollakiuria | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Proteinuria | 1/482 (0.2%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Renal colic | 0/482 (0%) | 3/485 (0.6%) | 0/485 (0%) | |||
| Renal cyst | 2/482 (0.4%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Renal failure | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Renal failure chronic | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Stress urinary incontinence | 2/482 (0.4%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Urethral disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Urinary incontinence | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Urinary retention | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Urinary tract inflammation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Urine flow decreased | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Atrophic vulvovaginitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Benign prostatic hyperplasia | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Breast cyst | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Breast disorder | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Breast pain | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Cervical polyp | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cystocele | 1/482 (0.2%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Endometrial hypertrophy | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Erectile dysfunction | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Erection increased | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Fallopian tube cyst | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Menopausal disorder | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Menstrual disorder | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Metrorrhagia | 1/482 (0.2%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Nipple pain | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Ovarian cyst | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Pelvic pain | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Postmenopausal haemorrhage | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Prostatitis | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Prostatomegaly | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Rectocele | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Sexual dysfunction | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Uterine enlargement | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Uterine polyp | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Uterine prolapse | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Vaginal discharge | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Vaginal haemorrhage | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Vaginal prolapse | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Vulvovaginal dryness | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Vulvovaginal pain | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Vulvovaginal pruritus | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Allergic bronchitis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Asthma | 4/482 (0.8%) | 7/485 (1.4%) | 3/485 (0.6%) | |||
| Asthma exercise induced | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Bronchitis chronic | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Bronchospasm | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Chronic obstructive pulmonary disease | 3/482 (0.6%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Cough | 10/482 (2.1%) | 9/485 (1.9%) | 8/485 (1.6%) | |||
| Dry throat | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Dysphonia | 2/482 (0.4%) | 2/485 (0.4%) | 3/485 (0.6%) | |||
| Dyspnoea | 2/482 (0.4%) | 4/485 (0.8%) | 3/485 (0.6%) | |||
| Dyspnoea exertional | 3/482 (0.6%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Emphysema | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Epistaxis | 0/482 (0%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Hypoventilation | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Interstitial lung disease | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Nasal congestion | 5/482 (1%) | 4/485 (0.8%) | 2/485 (0.4%) | |||
| Nasal polyps | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Nasal septum deviation | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Nasal turbinate hypertrophy | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Nocturnal dyspnoea | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Oropharyngeal discomfort | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Oropharyngeal pain | 7/482 (1.5%) | 7/485 (1.4%) | 5/485 (1%) | |||
| Paranasal sinus hypersecretion | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pleural effusion | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Pleurisy | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pleuritic pain | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Productive cough | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Pulmonary embolism | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Pulmonary hypertension | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Rales | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Respiratory disorder | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Respiratory tract congestion | 0/482 (0%) | 2/485 (0.4%) | 0/485 (0%) | |||
| Rhinitis allergic | 5/482 (1%) | 1/485 (0.2%) | 3/485 (0.6%) | |||
| Rhinitis perennial | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rhinorrhoea | 1/482 (0.2%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rhonchi | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Sinus congestion | 6/482 (1.2%) | 5/485 (1%) | 2/485 (0.4%) | |||
| Sleep apnoea syndrome | 2/482 (0.4%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Throat irritation | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Upper respiratory tract inflammation | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Upper-airway cough syndrome | 2/482 (0.4%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Vasomotor rhinitis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Wheezing | 2/482 (0.4%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Actinic keratosis | 4/482 (0.8%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Alopecia | 2/482 (0.4%) | 3/485 (0.6%) | 1/485 (0.2%) | |||
| Cold sweat | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Cutis laxa | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Dermal cyst | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Dermatitis | 3/482 (0.6%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Dermatitis allergic | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Dermatitis atopic | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Dermatitis contact | 3/482 (0.6%) | 3/485 (0.6%) | 8/485 (1.6%) | |||
| Drug eruption | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Dry skin | 2/482 (0.4%) | 0/485 (0%) | 0/485 (0%) | |||
| Eczema | 0/482 (0%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Erythema | 4/482 (0.8%) | 2/485 (0.4%) | 4/485 (0.8%) | |||
| Haemorrhage subcutaneous | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Hyperhidrosis | 4/482 (0.8%) | 2/485 (0.4%) | 4/485 (0.8%) | |||
| Hyperkeratosis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Hypertrichosis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Idiopathic urticaria | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Increased tendency to bruise | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Ingrowing nail | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Ingrown hair | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Mechanical urticaria | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Nail dystrophy | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Night sweats | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Onycholysis | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Papule | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Photodermatosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Pruritus | 1/482 (0.2%) | 5/485 (1%) | 5/485 (1%) | |||
| Psoriasis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rash | 13/482 (2.7%) | 12/485 (2.5%) | 8/485 (1.6%) | |||
| Rash erythematous | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Rash generalised | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Rash papular | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Rosacea | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Scab | 1/482 (0.2%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Seborrhoea | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Seborrhoeic dermatitis | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Skin lesion | 1/482 (0.2%) | 3/485 (0.6%) | 4/485 (0.8%) | |||
| Skin ulcer | 1/482 (0.2%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
| Subcutaneous nodule | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Urticaria | 1/482 (0.2%) | 3/485 (0.6%) | 2/485 (0.4%) | |||
| Vascular disorders | ||||||
| Aortic aneurysm | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Arteriosclerosis | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Bleeding varicose vein | 0/482 (0%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Deep vein thrombosis | 1/482 (0.2%) | 0/485 (0%) | 2/485 (0.4%) | |||
| Diastolic hypertension | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Flushing | 3/482 (0.6%) | 1/485 (0.2%) | 0/485 (0%) | |||
| Haematoma | 2/482 (0.4%) | 1/485 (0.2%) | 2/485 (0.4%) | |||
| Haemorrhage | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Hot flush | 2/482 (0.4%) | 1/485 (0.2%) | 4/485 (0.8%) | |||
| Hypertension | 34/482 (7.1%) | 27/485 (5.6%) | 19/485 (3.9%) | |||
| Hypertensive crisis | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Hypotension | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Phlebitis | 3/482 (0.6%) | 0/485 (0%) | 3/485 (0.6%) | |||
| Phlebitis deep | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Phlebitis superficial | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Systolic hypertension | 0/482 (0%) | 1/485 (0.2%) | 1/485 (0.2%) | |||
| Thrombophlebitis | 0/482 (0%) | 0/485 (0%) | 1/485 (0.2%) | |||
| Thrombophlebitis superficial | 1/482 (0.2%) | 0/485 (0%) | 0/485 (0%) | |||
| Varicose vein | 1/482 (0.2%) | 3/485 (0.6%) | 0/485 (0%) | |||
| Venous insufficiency | 4/482 (0.8%) | 2/485 (0.4%) | 1/485 (0.2%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00565812
Other Study ID Numbers:
- A6171016
- 2007-001457-26
- ITIC
First Posted:
Nov 30, 2007
Last Update Posted:
Dec 30, 2016
Last Verified:
Nov 1, 2016