A Study for Patients With Rheumatoid Arthritis on Methotrexate (MTX) With an Inadequate Response to TNFα Inhibitor Therapy
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00689728
Collaborator
(none)
100
45
3
23
2.2
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to explore whether LY2127399 is effective in relieving signs and symptoms of rheumatoid arthritis (RA) in patients with a history of inadequate response or intolerance to at least 1 Tumor Necrosis Factor-Alpha (TNFα) inhibitor therapy. Examples of these TNFα inhibitor therapies that are currently on the market include Enbrel® (etanercept), Remicade® (infliximab), and Humira® (adalimumab).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of Multiple Intravenous Doses of LY2127399 in Patients With Rheumatoid Arthritis on Concomitant Methotrexate and an Inadequate Response to TNFα Inhibitor Therapy
Study Start Date
:
Jun 1, 2008
Actual Primary Completion Date
:
Feb 1, 2010
Actual Study Completion Date
:
May 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 30 milligram (mg) LY2127399 Double-blind Treatment: 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. Rescue: At Week 16 primary endpoint, participants without at least 20% improvement in either tender or swollen joint counts based on 28 joints, could receive an additional (unblinded) 30 minute infusion of LY2127399 80 mg or remain on initial randomized treatment up to Week 24. Follow-up: Optional visits beyond Week 24, if needed, to assess safety including B cell count recovery. |
Biological: LY2127399
LY2127399 will be administered as a single IV infusion over 30 minutes.
|
| Experimental: 80 mg LY2127399 Double-blind Treatment: 80 mg LY2127399 administered as a single IV infusion over 30 minutes at 0, 3, and 6 weeks. Rescue: At Week 16 primary endpoint, participants without at least 20% improvement in either tender or swollen joint counts based on 28 joints, could receive an additional (unblinded) 30 minute infusion of LY2127399 80 mg or remain on initial randomized treatment up to Week 24. Follow-up: Optional visits beyond Week 24, if needed, to assess safety including B cell count recovery. |
Biological: LY2127399
LY2127399 will be administered as a single IV infusion over 30 minutes.
|
| Placebo Comparator: Placebo Double-blind Treatment: Placebo comparator administered as a single IV infusion over 30 minutes at 0, 3, and 6 weeks. Rescue: At Week 16 primary endpoint, participants without at least 20% improvement in either tender or swollen joint counts based on 28 joints could receive an additional (unblinded) 30 minute infusion of LY2127399 80 mg or remain on same initial randomized treatment up to Week 24. Follow-Up: Optional visits beyond Week 24, if needed, to assess safety including B cell count recovery. |
Drug: Placebo
Placebo will be administered as a single IV infusion over 30 minutes.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving American College of Rheumatology (ACR)50 Response at Week 16 [16 weeks]
ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. ACR50 Responder is defined as a participant with greater than 50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
Secondary Outcome Measures
- Number of Participants Experiencing An Adverse Event [Baseline up to 68 weeks]
Serious adverse events and other non-serious adverse events are located in the Reported Adverse Event section.
- Change From Baseline in Medical Outcome Study 36-Item Short Form Health Survey (SF-36) at Week 16 [Baseline, 16 weeks]
Self-reported questionnaire of 36 questions in 8 domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional, general health). Each domain is scored by summing individual items and transforming scores into a 0-100 scale (higher scores=better health status/function). The mental and physical component summaries are based on the 8 domains. Component scores are transformed scores representing a mean (50) and standard deviation (10) in the general United States (US) population. Scores > or <50 are above or below the average US population.
- Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response at Week 16 [16 weeks]
ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR20 Responder is defined as a participant with at least 20% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
- Percentage of Participants Achieving American College of Rheumatology (ACR)70 Response at Week 16 [16 weeks]
ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR70 Responder is defined as a participant with at least 70% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein.
- Change From Baseline in Tender Joint Count at Week 16 [Baseline, 16 weeks]
The number of tender and painful joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as tender or not tender.
- Change From Baseline in Swollen Joint Count at Week 16 [Baseline, 16 weeks]
The number of swollen joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as swollen or not swollen.
- Change From Baseline in Participant's Assessment of Joint Pain at Week 16 [Baseline, 16 weeks]
Participant's assessment of joint pain using a visual analog scale (VAS), which ranged from 0 to 100 millimeters, where 0 indicated no pain and 100 indicated worst possible pain.
- Change From Baseline in Participant's Assessment of Disease Activity at Week 16 [Baseline, 16 weeks]
Participant's assessment of their current arthritis disease activity using a visual analog scale (VAS), which ranged from 0 to 100 millimeters, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis.
- Change From Baseline in Physician's Global Assessment of Disease Activity at Week 16 [Baseline, 16 weeks]
Physician's global assessment of arthritis disease activity using a visual analog scale (VAS) which ranged from 0 to 100 millimeters, where 0 indicates no arthritis activity and 100 indicates extremely active arthritis.
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 [Baseline, 16 weeks]
The HAQ-DI questionnaire scores the participant's self-perception on the degree of difficulty when dressing and grooming, arising, eating, walking, hygiene, reach, grip, and performing other daily activities (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do). The scores for each of the functional areas, which have a range from 0 to 3, are averaged to calculate the functional disability index. Higher scores are associated with greater disability.
- Percent Change From Baseline in C-reactive Protein (CRP) at Week 16 [Baseline, 16 weeks]
- Change From Baseline in Disease Activity Score (DAS28) at Week 16 [Baseline, 16 weeks]
Disease Activity Score (modified to include the 28 joint count [DAS28]) consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (patient global VAS). It is calculated by using the following formula:DAS28-CRP=0.56 times the square root of(28TJC)+0.28 times the square root of(28SJC)+0.36*natural log (ln)(CRP+1)+0.014*patient global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
- Number of Participants With Response (Response Rate) Based Upon European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) at Week 16 [16 weeks]
EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28 joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (patient global VAS). EULAR28 categories include: No Response (improvement in DAS28 of less than or equal to 0.6 units or post-baseline DAS28 score greater than 5.1 with improvement by less than or equal to 1.2 units), Moderate Response (post-baseline DAS28 score less than or equal to 5.1 with improvement by more than 0.6 units but no greater than 1.2 units or post-baseline DAS28 score greater than 3.2 with improvement by more than 1.2 units), and Good Response (post-baseline DAS28 score less than or equal to 3.2 with improvement by more than 1.2 units).
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 16 [Baseline, 16 weeks]
The FACIT Fatigue Score is a brief patient-reported measure of fatigue and consists of 13 items. Scores range from 0 to 52, with higher scores indicating less fatigue.
- Pharmacodynamics: Change From Baseline in Absolute CD20 + B Cell Count at Week 16 [Baseline, 16 weeks]
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. For this endpoint, total B cell counts (CD20+CD3- cells) are represented by number of cells per microliter. The reference range for the absolute counts is 43-602 cells per microliter.
- Pharmacodynamics: Change From Baseline in Total B Cells (CD20 + CD3-) as a Percentage of Total Lymphocytes [Baseline, 16 weeks]
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. For this outcome, total B cells (CD20+CD3- cells) are expressed as the relative percent of lymphocytes. There is no reference range provided for this parameter by the performing laboratory.
- Pharmacodynamics: Change From Baseline in Serum Immunoglobulins at Week 16 [Baseline, 16 weeks]
Serum immunoglobulin measured by Immunoglobulin A (IgA), Immunoglobulin G (IgG), and Immunoglobulin M (IgM) levels.
- Pharmacokinetics: Predicted Population Mean Parameter: C-trough Steady-state [Pre-dose, Day 1 through Week 24]
C-trough is defined as the concentration of LY at the end of the dosing interval at steady state. Mean C-trough value was obtained by conducting a simulation consisting of 1000 participants. The simulated data were then used to determine the noncompartmental PK parameters for each regimen. Mean and standard deviation of the Ctrough values were calculated for each dose group based on simulated data.
- Pharmacokinetics: Predicted Population Mean Parameter: T-half Life (t1/2, Tau) [Pre-dose, Day 1 through Week 24]
T-half life (t1/2, tau) is defined as the apparent steady state elimination within the dosing interval. T-half life was obtained by conducting a simulation consisting of 1000 participants using the study drug regimens (30 and 80 mg, intravenous infusion over 30 minutes, once every 3 weeks). The simulated data were then used to determine the noncompartmental PK parameters for each regimen. Mean and standard deviation of the t-half life values were calculated for each dose group based on simulated data.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have given written informed consent approval
-
Women must not be at risk to become pregnant during study participation
-
Diagnosis of Rheumatoid Arthritis
-
Active Rheumatoid Arthritis
-
Current, regular use of Methotrexate, at a stable dose
-
Have been on at least 1 biologic tumor necrosis factor-alpha (TNFα) inhibitor therapy and either failed or were intolerant to treatment
-
Other criteria to be reviewed by study doctor
Exclusion Criteria:
-
Use of excluded medications (reviewed by study doctor)
-
Have medical findings which, in the opinion of the study doctor, put patient at an unacceptable risk for participation in the study
-
Have had recent or ongoing infection which, in the opinion of the study doctor put patient at an unacceptable risk for participation
-
Evidence of tuberculosis
-
Have systemic inflammatory condition other than rheumatoid arthritis (RA), such as juvenile RA, seronegative spondyloarthropathy, Crohn's disease, ulcerative colitis, or psoriatic arthritis.
-
Other criteria to be reviewed by study doctor
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Birmingham | Alabama | United States | 35205 |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mesa | Arizona | United States | 85208 |
| 3 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Palm Desert | California | United States | 92260 |
| 4 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Riverside | California | United States | 92501 |
| 5 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Santa Maria | California | United States | 93454 |
| 6 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Upland | California | United States | 91786 |
| 7 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Jupiter | Florida | United States | 33458 |
| 8 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Vero Beach | Florida | United States | 32960 |
| 9 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Zephyrhills | Florida | United States | 33542 |
| 10 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Baltimore | Maryland | United States | 21239 |
| 11 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Saint Louis | Missouri | United States | 63141 |
| 12 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hickory | North Carolina | United States | 28601 |
| 13 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Middleburg Heights | Ohio | United States | 44130 |
| 14 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Philadelphia | Pennsylvania | United States | 19152 |
| 15 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Orangeburg | South Carolina | United States | 29118 |
| 16 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Memphis | Tennessee | United States | 38119 |
| 17 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Austin | Texas | United States | 78705 |
| 18 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dallas | Texas | United States | 75235 |
| 19 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mesquite | Texas | United States | 75150 |
| 20 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Buenos Aires | Argentina | C1055AAF | |
| 21 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Caba | Argentina | C1180AAX | |
| 22 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Juan | Argentina | 5400 | |
| 23 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tucuman | Argentina | 4000 | |
| 24 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Vienna | Austria | 1100 | |
| 25 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Liege | Belgium | 4000 | |
| 26 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Campinas | Brazil | 13015-011 | |
| 27 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Curitiba | Brazil | 80060-240 | |
| 28 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Goiania | Brazil | 74605-050 | |
| 29 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Porto Alegre | Brazil | 90610-970 | |
| 30 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Setor Oeste/Goiania | Brazil | 74110-010 | |
| 31 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Winnipeg | Manitoba | Canada | R3A 1M4 |
| 32 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hamilton | Ontario | Canada | N2M 5N6 |
| 33 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kitchener | Ontario | Canada | N2M 5N6 |
| 34 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Gottingen | Germany | 37075 | |
| 35 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hildesheim | Germany | 31134 | |
| 36 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Vogelsang | Germany | 39245 | |
| 37 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chihuahua | Mexico | 31000 | |
| 38 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Cuernavaca | Mexico | 62270 | |
| 39 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Guadalajara | Mexico | 44100 | |
| 40 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Monterrey | Mexico | 64020 | |
| 41 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Morelia | Mexico | 58240 | |
| 42 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lublin | Poland | 20-954 | |
| 43 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Torun | Poland | 87-100 | |
| 44 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Warsaw | Poland | 00-235 | |
| 45 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Juan | Puerto Rico | 00918 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00689728
Other Study ID Numbers:
- 11351
- H9B-MC-BCDG
First Posted:
Jun 4, 2008
Last Update Posted:
Dec 6, 2018
Last Verified:
Nov 1, 2018
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Double-blind treatment was administered at Weeks 0, 3, and 6. At Week 16, participants not having at least a 20% decrease in tender or swollen joint counts could receive rescue therapy. Post-study B-cell follow-up (safety only) occurred beyond Week 24. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | Double-blind: 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. Rescue: either remain on 30 mg LY2127399 or receive 80 mg LY2127399 up to Week 24. Optional Follow-up: assessing safety after Week 24, if needed. | Double-blind: 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. Rescue: remain on 80 mg LY2127399 up to Week 24. Optional Follow-up: assessing safety after Week 24, if needed. | Double-blind: Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. Rescue: either remain on placebo or receive 80 mg LY2127399 up to Week 24. Optional Follow-up: assessing safety after Week 24, if needed. |
| Period Title: Double-Blind Treatment | |||
| STARTED | 35 | 30 | 35 |
| COMPLETED | 31 | 26 | 30 |
| NOT COMPLETED | 4 | 4 | 5 |
| Period Title: Double-Blind Treatment | |||
| STARTED | 31 | 26 | 30 |
| COMPLETED | 30 | 24 | 29 |
| NOT COMPLETED | 1 | 2 | 1 |
| Period Title: Double-Blind Treatment | |||
| STARTED | 9 | 11 | 10 |
| COMPLETED | 6 | 5 | 4 |
| NOT COMPLETED | 3 | 6 | 6 |
Baseline Characteristics
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Total of all reporting groups |
| Overall Participants | 35 | 30 | 35 | 100 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
52.4
(13.03)
|
52.7
(14.05)
|
52.2
(11.46)
|
52.4
(12.70)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
28
80%
|
26
86.7%
|
32
91.4%
|
86
86%
|
| Male |
7
20%
|
4
13.3%
|
3
8.6%
|
14
14%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Caucasian |
26
74.3%
|
20
66.7%
|
21
60%
|
67
67%
|
| African |
3
8.6%
|
3
10%
|
8
22.9%
|
14
14%
|
| Hispanic |
6
17.1%
|
7
23.3%
|
6
17.1%
|
19
19%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
18
51.4%
|
18
60%
|
14
40%
|
50
50%
|
| Puerto Rico |
0
0%
|
0
0%
|
1
2.9%
|
1
1%
|
| Canada |
2
5.7%
|
1
3.3%
|
1
2.9%
|
4
4%
|
| Argentina |
4
11.4%
|
4
13.3%
|
4
11.4%
|
12
12%
|
| Poland |
1
2.9%
|
1
3.3%
|
4
11.4%
|
6
6%
|
| Belgium |
0
0%
|
1
3.3%
|
0
0%
|
1
1%
|
| Brazil |
6
17.1%
|
3
10%
|
6
17.1%
|
15
15%
|
| Austria |
2
5.7%
|
2
6.7%
|
3
8.6%
|
7
7%
|
| Germany |
2
5.7%
|
0
0%
|
2
5.7%
|
4
4%
|
Outcome Measures
| Title | Percentage of Participants Achieving American College of Rheumatology (ACR)50 Response at Week 16 |
|---|---|
| Description | ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. ACR50 Responder is defined as a participant with greater than 50% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein. |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Non-responder imputation/last observation carried forward (NRI/LOCF); intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline ACR50 assessment. Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 | 35 |
| Number [Percentage of Participants] |
11.4
32.6%
|
14.3
47.7%
|
2.9
8.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.178 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.116 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Number of Participants Experiencing An Adverse Event |
|---|---|
| Description | Serious adverse events and other non-serious adverse events are located in the Reported Adverse Event section. |
| Time Frame | Baseline up to 68 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population defined as all participants who were randomized and received at least one dose of study drug. |
| Arm/Group Title | 30 mg LY2127399 - Treatment | 80 mg LY2127399 - Treatment | Placebo - Treatment | 30 mg LY2127399 - Without Rescue Treatment | 30 mg LY2127399 - With Rescue Treatment | 80 mg LY2127399 - Without Rescue Treatment | 80 mg LY2127399 - With Rescue Treatment | Placebo - Without Rescue Treatment | Placebo - With Rescue Treatment | 30 mg LY2127399 - Follow Up | 80 mg LY2127399 - Follow Up | Placebo - Follow Up |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Participants who were randomized to LY2127399 30 mg during Treatment Phase who did not have an improvement of at least 20% in either their tender or their swollen joint counts, based on 28 joints at Week 16 assessments and chose to receive optional rescue treatment of an additional 30 minute infusion of LY2127399 80 mg at Week 16. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Participants who were randomized to LY2127399 80 mg during Treatment Phase who did not have an improvement of at least 20% in either their tender or their swollen joint counts, based on 28 joints at Week 16 assessments and chose to receive optional rescue treatment of an additional 30 minute infusion of LY2127399 80 mg at Week 16. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Participants who were randomized to placebo during Treatment Phase who did not have an improvement of at least 20% in either their tender or their swollen joint counts, based on 28 joints at Week 16 assessments and chose to receive optional rescue treatment of an additional 30 minute infusion of LY2127399 80 mg at Week 16. | Participants who were randomized to LY2127399 30 mg during Treatment Phase who required additional follow-up for monitoring of their B cell counts, regardless of whether or not they received optional rescue treatment of an additional 30 minute infusion of LY2127399 80 mg at Week 16. | Participants who were randomized to LY2127399 80 mg during Treatment Phase who required additional follow-up for monitoring of their B cell counts, regardless of whether or not they received optional rescue treatment of an additional 30 minute infusion of LY2127399 80 mg at Week 16. | Participants who were randomized to placebo during Treatment Phase who required additional follow-up for monitoring of their B cell counts, regardless of whether or not they received optional rescue treatment of an additional 30 minute infusion of LY2127399 80 mg at Week 16. |
| Measure Participants | 35 | 30 | 35 | 19 | 12 | 15 | 11 | 10 | 20 | 9 | 11 | 10 |
| Serious |
1
2.9%
|
2
6.7%
|
3
8.6%
|
0
0%
|
1
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
| Other |
22
62.9%
|
21
70%
|
22
62.9%
|
2
2%
|
5
NaN
|
6
NaN
|
3
NaN
|
3
NaN
|
11
NaN
|
1
NaN
|
4
NaN
|
1
NaN
|
| Title | Change From Baseline in Medical Outcome Study 36-Item Short Form Health Survey (SF-36) at Week 16 |
|---|---|
| Description | Self-reported questionnaire of 36 questions in 8 domains (physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional, general health). Each domain is scored by summing individual items and transforming scores into a 0-100 scale (higher scores=better health status/function). The mental and physical component summaries are based on the 8 domains. Component scores are transformed scores representing a mean (50) and standard deviation (10) in the general United States (US) population. Scores > or <50 are above or below the average US population. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline SF-36 assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 34 | 27 | 34 |
| Physical Health |
5.064
(8.73)
|
5.197
(8.36)
|
1.229
(6.18)
|
| Mental Health |
2.700
(10.82)
|
3.597
(11.96)
|
0.133
(12.99)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.062 |
| Comments | p-value represents change from baseline at 16 weeks for LY2127399 30 mg. vs. placebo in Physical Health Component scores. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.873 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.052 |
| Comments | p-value represents change from baseline at 16 weeks for LY2127399 80 mg. vs. placebo in Physical Health Component scores. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 5.427 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.655 |
| Comments | p-value represents change from baseline at 16 weeks for LY2127399 30 mg. vs. placebo in Mental Health Component scores. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.720 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.173 |
| Comments | p-value represents change from baseline at 16 weeks for LY2127399 80 mg. vs. placebo in Mental Health Component scores. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.264 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response at Week 16 |
|---|---|
| Description | ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR20 Responder is defined as a participant with at least 20% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein. |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Non-responder imputation (NRI)/last observation carried forward; intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline ACR20 assessment. Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 | 35 |
| Number [Percentage of Participants] |
25.7
73.4%
|
28.6
95.3%
|
17.1
48.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.281 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.218 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants Achieving American College of Rheumatology (ACR)70 Response at Week 16 |
|---|---|
| Description | ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis. An ACR70 Responder is defined as a participant with at least 70% improvement from baseline in both tender and swollen joint counts and in at least 3 of the following 5 criteria: physician global assessment, patient global assessment, functional ability measure (Health Assessment Questionnaire-Disability Index which measures participants' perceived degree of difficulty when performing various daily activities), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein. |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Non-responder imputation (NRI)/last observation carried forward; intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline ACR70 assessment. Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 | 35 |
| Number [Percentage of Participants] |
2.9
8.3%
|
3.6
12%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.500 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.444 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline in Tender Joint Count at Week 16 |
|---|---|
| Description | The number of tender and painful joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as tender or not tender. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline tender joint assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 | 35 |
| Mean (Standard Deviation) [Tender Joints] |
-4.5
(6.74)
|
-6.3
(4.96)
|
-3.3
(8.20)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.337 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.5 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.038 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -6.6 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Swollen Joint Count at Week 16 |
|---|---|
| Description | The number of swollen joints is determined by examination of 28 joints (14 on each side) which include: the 2 shoulders, the 2 elbows, the 2 wrists, the 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees. The joints are assessed and classified as swollen or not swollen. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline swollen joint assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 | 35 |
| Mean (Standard Deviation) [Swollen Joints] |
-2.6
(5.23)
|
-4.7
(4.44)
|
-2.3
(5.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.403 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.7 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.3 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Participant's Assessment of Joint Pain at Week 16 |
|---|---|
| Description | Participant's assessment of joint pain using a visual analog scale (VAS), which ranged from 0 to 100 millimeters, where 0 indicated no pain and 100 indicated worst possible pain. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline joint pain assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 | 35 |
| Mean (Standard Deviation) [Millimeters] |
-16.1
(26.86)
|
-17.8
(27.10)
|
-9.1
(29.20)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.168 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -16.2 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.075 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -19.3 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Participant's Assessment of Disease Activity at Week 16 |
|---|---|
| Description | Participant's assessment of their current arthritis disease activity using a visual analog scale (VAS), which ranged from 0 to 100 millimeters, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline disease activity assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 26 | 35 |
| Mean (Standard Deviation) [Millimeters] |
-20.2
(25.87)
|
-23.6
(29.36)
|
-11.2
(29.05)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.157 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -19.3 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.025 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -25.6 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Physician's Global Assessment of Disease Activity at Week 16 |
|---|---|
| Description | Physician's global assessment of arthritis disease activity using a visual analog scale (VAS) which ranged from 0 to 100 millimeters, where 0 indicates no arthritis activity and 100 indicates extremely active arthritis. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline physician's disease activity assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 27 | 35 |
| Mean (Standard Deviation) [Millimeters] |
-17.7
(22.55)
|
-17.3
(29.67)
|
-13.1
(26.40)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.110 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -19.4 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.147 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -19.1 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 |
|---|---|
| Description | The HAQ-DI questionnaire scores the participant's self-perception on the degree of difficulty when dressing and grooming, arising, eating, walking, hygiene, reach, grip, and performing other daily activities (0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do). The scores for each of the functional areas, which have a range from 0 to 3, are averaged to calculate the functional disability index. Higher scores are associated with greater disability. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline HAQ-DI assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 | 35 |
| Mean (Standard Deviation) [Units on a Scale] |
-0.161
(0.569)
|
-0.259
(0.623)
|
-0.205
(0.511)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.969 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.172 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.452 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.280 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline in C-reactive Protein (CRP) at Week 16 |
|---|---|
| Description | |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline CRP assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 27 | 35 |
| Mean (Standard Deviation) [Percent Change] |
58.88
(216.005)
|
15.14
(123.625)
|
71.64
(410.942)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.554 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.920 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Disease Activity Score (DAS28) at Week 16 |
|---|---|
| Description | Disease Activity Score (modified to include the 28 joint count [DAS28]) consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (patient global VAS). It is calculated by using the following formula:DAS28-CRP=0.56 times the square root of(28TJC)+0.28 times the square root of(28SJC)+0.36*natural log (ln)(CRP+1)+0.014*patient global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline DAS28 assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 26 | 34 |
| Mean (Standard Deviation) [Units on a Scale] |
-0.911
(1.137)
|
-1.288
(0.934)
|
-0.613
(1.041)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.100 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.912 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.322 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Response (Response Rate) Based Upon European League Against Rheumatism Responder Index, 28 Joint Count (EULAR28) at Week 16 |
|---|---|
| Description | EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28 joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP), and participant global assessment of their disease activity (patient global VAS). EULAR28 categories include: No Response (improvement in DAS28 of less than or equal to 0.6 units or post-baseline DAS28 score greater than 5.1 with improvement by less than or equal to 1.2 units), Moderate Response (post-baseline DAS28 score less than or equal to 5.1 with improvement by more than 0.6 units but no greater than 1.2 units or post-baseline DAS28 score greater than 3.2 with improvement by more than 1.2 units), and Good Response (post-baseline DAS28 score less than or equal to 3.2 with improvement by more than 1.2 units). |
| Time Frame | 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline EULAR28 assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 26 | 34 |
| Good response |
5
14.3%
|
5
16.7%
|
0
0%
|
| Moderate response |
8
22.9%
|
12
40%
|
15
42.9%
|
| No response |
22
62.9%
|
9
30%
|
19
54.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.022 |
| Comments | p-value represents comparison of LY2127399-30 mg dose versus placebo for the 3 levels of EULAR response (good response, moderate response, no response). | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.016 |
| Comments | p-value represents comparison of LY2127399-80 mg dose versus placebo for the 3 levels of EULAR response (good response, moderate response, no response). | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 16 |
|---|---|
| Description | The FACIT Fatigue Score is a brief patient-reported measure of fatigue and consists of 13 items. Scores range from 0 to 52, with higher scores indicating less fatigue. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline FACIT assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 34 | 27 | 34 |
| Mean (Standard Deviation) [Units on a Scale] |
2.5
(11.20)
|
7.9
(8.44)
|
3.1
(9.56)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.818 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.6 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.066 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 7.7 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Pharmacodynamics: Change From Baseline in Absolute CD20 + B Cell Count at Week 16 |
|---|---|
| Description | B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. For this endpoint, total B cell counts (CD20+CD3- cells) are represented by number of cells per microliter. The reference range for the absolute counts is 43-602 cells per microliter. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline CD20 assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 32 | 26 | 33 |
| Mean (Standard Deviation) [Cells per Microliter] |
-30.94
(152.813)
|
-34.92
(82.090)
|
0.79
(144.251)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.010 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.056 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Pharmacodynamics: Change From Baseline in Total B Cells (CD20 + CD3-) as a Percentage of Total Lymphocytes |
|---|---|
| Description | B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B-cells. For this outcome, total B cells (CD20+CD3- cells) are expressed as the relative percent of lymphocytes. There is no reference range provided for this parameter by the performing laboratory. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline CD20 assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 32 | 26 | 33 |
| Mean (Standard Deviation) [Percentage of Lymphocytes] |
-2.26
(4.651)
|
-2.20
(4.517)
|
-0.59
(4.856)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.015 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Pharmacodynamics: Change From Baseline in Serum Immunoglobulins at Week 16 |
|---|---|
| Description | Serum immunoglobulin measured by Immunoglobulin A (IgA), Immunoglobulin G (IgG), and Immunoglobulin M (IgM) levels. |
| Time Frame | Baseline, 16 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention to treat (ITT) population defined as participants who were randomized, received at least one dose of study drug, and had at least one post-baseline serum immunoglobulin assessment; last observation carried forward (LOCF). Two participants from sites with good clinical practice [GCP] violations are excluded. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 | Placebo |
|---|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 34 | 28 | 35 |
| Immunoglobulin G |
-0.83
(1.233)
|
-1.33
(2.055)
|
-0.62
(1.783)
|
| Immunoglobulin M |
-0.27
(0.325)
|
-0.24
(0.371)
|
-0.05
(0.388)
|
| Immunoglobulin A |
-0.24
(0.429)
|
-0.26
(0.405)
|
-0.23
(0.729)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.146 |
| Comments | p-value is for Immunoglobulin G change at week 16 (LOCF) | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.125 |
| Comments | p-value is for Immunoglobulin G change at week 16 (LOCF) | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | p-value is for Immunoglobulin M change at week 16 (LOCF) | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | p-value is for Immunoglobulin M change at week 16 (LOCF) | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 30 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.115 |
| Comments | p-value is for Immunoglobulin A change at week 16 (LOCF) | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 80 mg LY2127399, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.019 |
| Comments | p-value is for Immunoglobulin A change at week 16 (LOCF) | |
| Method | ANCOVA | |
| Comments | ||
| Title | Pharmacokinetics: Predicted Population Mean Parameter: C-trough Steady-state |
|---|---|
| Description | C-trough is defined as the concentration of LY at the end of the dosing interval at steady state. Mean C-trough value was obtained by conducting a simulation consisting of 1000 participants. The simulated data were then used to determine the noncompartmental PK parameters for each regimen. Mean and standard deviation of the Ctrough values were calculated for each dose group based on simulated data. |
| Time Frame | Pre-dose, Day 1 through Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with evaluable PK C-trough data. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 |
|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 |
| Mean (Standard Deviation) [Micrograms per Milliliter] |
5.84
(2.87)
|
18.9
(7.86)
|
| Title | Pharmacokinetics: Predicted Population Mean Parameter: T-half Life (t1/2, Tau) |
|---|---|
| Description | T-half life (t1/2, tau) is defined as the apparent steady state elimination within the dosing interval. T-half life was obtained by conducting a simulation consisting of 1000 participants using the study drug regimens (30 and 80 mg, intravenous infusion over 30 minutes, once every 3 weeks). The simulated data were then used to determine the noncompartmental PK parameters for each regimen. Mean and standard deviation of the t-half life values were calculated for each dose group based on simulated data. |
| Time Frame | Pre-dose, Day 1 through Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with evaluable PK t-half life data. |
| Arm/Group Title | 30 mg LY2127399 | 80 mg LY2127399 |
|---|---|---|
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. |
| Measure Participants | 35 | 28 |
| Mean (Standard Deviation) [Days] |
19
(8)
|
22
(8)
|
Adverse Events
| Time Frame | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||||||
| Arm/Group Title | 30 mg LY2127399 - Treatment | 80 mg LY2127399 - Treatment | Placebo - Treatment | 30 mg LY2127399 - Without Rescue Treatment | 30 mg LY2127399 - With Rescue Treatment | 80 mg LY2127399 - Without Rescue Treatment | 80 mg LY2127399 - With Rescue Treatment | Placebo - Without Rescue Treatment | Placebo - With Rescue Treatment | 30 mg LY2127399 - Follow-up | 80 mg LY2127399 - Follow-up | Placebo - Follow-up | ||||||||||||
| Arm/Group Description | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | 30 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Participants who were randomized to 30 mg LY2127399 during Treatment Phase who did not have an improvement of at least 20% in either their tender or their swollen joint counts, based on 28 joints at Week 16 assessments and chose to receive optional rescue treatment of an additional 30 minute infusion of 80 mg LY2127399 at Week 16. | 80 mg LY2127399 administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Participants who were randomized to 80 mg LY2127399 during Treatment Phase who did not have an improvement of at least 20% in either their tender or their swollen joint counts, based on 28 joints at Week 16 assessments and chose to receive optional rescue treatment of an additional 30 minute infusion of 80 mg LY2127399 at Week 16. | Placebo comparator administered as a single intravenous (IV) infusion over 30 minutes at 0, 3, and 6 weeks. | Participants who were randomized to placebo during Treatment Phase who did not have an improvement of at least 20% in either their tender or their swollen joint counts, based on 28 joints at Week 16 assessments and chose to receive optional rescue treatment of an additional 30 minute infusion of 80 mg LY2127399 at Week 16. | Participants who were randomized to 30 mg LY2127399 during Treatment Phase who required additional follow-up for monitoring of their B cell counts, regardless of whether or not they received optional rescue treatment of an additional 30 minute infusion of 80 mg LY2127399 at Week 16. | Participants who were randomized to 80 mg LY2127399 during Treatment Phase who required additional follow-up for monitoring of their B cell counts, regardless of whether or not they received optional rescue treatment of an additional 30 minute infusion of 80 mg LY2127399 at Week 16. | Participants who were randomized to placebo during Treatment Phase who required additional follow-up for monitoring of their B cell counts, regardless of whether or not they received optional rescue treatment of an additional 30 minute infusion of 80 mg LY2127399 at Week 16. | ||||||||||||
All Cause Mortality |
||||||||||||||||||||||||
| 30 mg LY2127399 - Treatment | 80 mg LY2127399 - Treatment | Placebo - Treatment | 30 mg LY2127399 - Without Rescue Treatment | 30 mg LY2127399 - With Rescue Treatment | 80 mg LY2127399 - Without Rescue Treatment | 80 mg LY2127399 - With Rescue Treatment | Placebo - Without Rescue Treatment | Placebo - With Rescue Treatment | 30 mg LY2127399 - Follow-up | 80 mg LY2127399 - Follow-up | Placebo - Follow-up | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||||
Serious Adverse Events |
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| 30 mg LY2127399 - Treatment | 80 mg LY2127399 - Treatment | Placebo - Treatment | 30 mg LY2127399 - Without Rescue Treatment | 30 mg LY2127399 - With Rescue Treatment | 80 mg LY2127399 - Without Rescue Treatment | 80 mg LY2127399 - With Rescue Treatment | Placebo - Without Rescue Treatment | Placebo - With Rescue Treatment | 30 mg LY2127399 - Follow-up | 80 mg LY2127399 - Follow-up | Placebo - Follow-up | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/35 (2.9%) | 2/30 (6.7%) | 3/35 (8.6%) | 0/19 (0%) | 1/12 (8.3%) | 0/15 (0%) | 0/11 (0%) | 0/10 (0%) | 0/20 (0%) | 0/9 (0%) | 0/11 (0%) | 0/10 (0%) | ||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Constipation | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Crohn's disease | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||
| Gastroenteritis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rhinitis | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Tracheitis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Back injury | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Chest injury | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Heart injury | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Hypokalaemia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Arthralgia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rheumatoid arthritis | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Spondylolisthesis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||
| Dizziness | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Hyperkeratosis | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
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| 30 mg LY2127399 - Treatment | 80 mg LY2127399 - Treatment | Placebo - Treatment | 30 mg LY2127399 - Without Rescue Treatment | 30 mg LY2127399 - With Rescue Treatment | 80 mg LY2127399 - Without Rescue Treatment | 80 mg LY2127399 - With Rescue Treatment | Placebo - Without Rescue Treatment | Placebo - With Rescue Treatment | 30 mg LY2127399 - Follow-up | 80 mg LY2127399 - Follow-up | Placebo - Follow-up | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/35 (62.9%) | 21/30 (70%) | 22/35 (62.9%) | 2/19 (10.5%) | 5/12 (41.7%) | 6/15 (40%) | 3/11 (27.3%) | 3/10 (30%) | 11/20 (55%) | 1/9 (11.1%) | 4/11 (36.4%) | 1/10 (10%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Anaemia | 0/35 (0%) | 0 | 3/30 (10%) | 3 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Thrombocytosis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||||||||||
| Arrhythmia | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Palpitations | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Endocrine disorders | ||||||||||||||||||||||||
| Hypothyroidism | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 1/9 (11.1%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Eye disorders | ||||||||||||||||||||||||
| Eye pain | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Photophobia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Vision blurred | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Abdominal pain lower | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Abdominal pain upper | 2/35 (5.7%) | 2 | 2/30 (6.7%) | 2 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Diarrhoea | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Gastrointestinal pain | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Haemorrhoids | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hiatus hernia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Mouth ulceration | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Nausea | 0/35 (0%) | 0 | 2/30 (6.7%) | 2 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Odynophagia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 1/10 (10%) | 1 |
| Vomiting | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| General disorders | ||||||||||||||||||||||||
| Chest pain | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Fatigue | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Generalised oedema | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Infusion site phlebitis | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Non-cardiac chest pain | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Oedema peripheral | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Pyrexia | 2/35 (5.7%) | 2 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||||||||||
| Hepatic cyst | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hepatic mass | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Immune system disorders | ||||||||||||||||||||||||
| Drug hypersensitivity | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||||
| Bronchitis | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 1/19 (5.3%) | 1 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Cellulitis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 1/10 (10%) | 1 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Cellulitis of male external genital organ | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Ear infection | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 1/10 (10%) | 1 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Gastroenteritis | 1/35 (2.9%) | 1 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Gastroenteritis viral | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Granuloma inguinale | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Influenza | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Nasopharyngitis | 3/35 (8.6%) | 3 | 0/30 (0%) | 0 | 2/35 (5.7%) | 2 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Oral herpes | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Pharyngitis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 1/10 (10%) | 1 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Pneumonia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Rhinitis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Sinusitis | 2/35 (5.7%) | 2 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Staphylococcal impetigo | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Tonsillitis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Tooth infection | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Upper respiratory tract infection | 2/35 (5.7%) | 2 | 3/30 (10%) | 3 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Urethritis | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Urinary tract infection | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 2/20 (10%) | 2 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Clavicle fracture | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Contusion | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Foot fracture | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rib fracture | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Thermal burn | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Traumatic ulcer | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Investigations | ||||||||||||||||||||||||
| Alanine aminotransferase increased | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Blood pressure increased | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hepatic enzyme increased | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Laboratory test abnormal | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Liver function test abnormal | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Lymph node palpable | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Weight decreased | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Decreased appetite | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Diabetes mellitus | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Glucose tolerance impaired | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Gout | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Hyperlipidaemia | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hypokalaemia | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Type 2 diabetes mellitus | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Arthralgia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Back pain | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Bursitis | 2/35 (5.7%) | 3 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Intervertebral disc protrusion | 0/35 (0%) | 0 | 2/30 (6.7%) | 2 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Muscle spasms | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Myalgia | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Osteoarthritis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rheumatoid arthritis | 4/35 (11.4%) | 4 | 2/30 (6.7%) | 2 | 8/35 (22.9%) | 8 | 1/19 (5.3%) | 1 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 2/11 (18.2%) | 2 | 1/10 (10%) | 1 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 |
| Spondylolisthesis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Tendonitis | 1/35 (2.9%) | 2 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Tenosynovitis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
| Benign neoplasm of adrenal gland | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Spinal haemangioma | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||||||||
| Carpal tunnel syndrome | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Depressed level of consciousness | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Dizziness | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Headache | 1/35 (2.9%) | 1 | 3/30 (10%) | 3 | 2/35 (5.7%) | 2 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Lumbar radiculopathy | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Paraesthesia | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Syncope | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||||||||||
| Anxiety | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Depression | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Insomnia | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 1/11 (9.1%) | 1 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||||||||||
| Dysuria | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Haematuria | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Renal colic | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Renal cyst | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||||||||
| Ovarian cyst | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Prostatitis | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Asthma | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Chronic obstructive pulmonary disease | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Cough | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 1/35 (2.9%) | 2 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Epistaxis | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Oropharyngeal pain | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 1/19 (5.3%) | 1 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rhinitis allergic | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Acne | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Alopecia | 2/35 (5.7%) | 3 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Dermatitis allergic | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hyperhidrosis | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hyperkeratosis | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Pruritus | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rash | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rash maculo-papular | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Rash papular | 2/35 (5.7%) | 2 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Skin exfoliation | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Skin ulcer | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Trichorrhexis | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Urticaria | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Social circumstances | ||||||||||||||||||||||||
| Ex-tobacco user | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Surgical and medical procedures | ||||||||||||||||||||||||
| Bladder repair | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hysterectomy | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 1/12 (8.3%) | 1 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Vascular disorders | ||||||||||||||||||||||||
| Aortic aneurysm | 0/35 (0%) | 0 | 1/30 (3.3%) | 1 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hot flush | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hypertension | 2/35 (5.7%) | 2 | 1/30 (3.3%) | 1 | 2/35 (5.7%) | 2 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Hypotension | 0/35 (0%) | 0 | 0/30 (0%) | 0 | 1/35 (2.9%) | 1 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Peripheral vascular disorder | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
| Poor venous access | 1/35 (2.9%) | 1 | 0/30 (0%) | 0 | 0/35 (0%) | 0 | 0/19 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 | 0/11 (0%) | 0 | 0/10 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00689728
Other Study ID Numbers:
- 11351
- H9B-MC-BCDG
First Posted:
Jun 4, 2008
Last Update Posted:
Dec 6, 2018
Last Verified:
Nov 1, 2018