Treatment of Pain Associated With Fibromyalgia
Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02187471
Collaborator
Syneos Health (Other)
1,301
154
4
23.9
8.4
0.4
Study Details
Study Description
Brief Summary
The main objective of this trial is to compare change in weekly average daily pain score (ADPS) from baseline to Week 13 in participants receiving either dose of DS-5565 versus placebo.
Weekly ADPS is based on daily pain scores reported by the subject that best describes his or her worst pain over the previous 24 hours.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1301 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo- and Active-Controlled Study of DS-5565 for Treatment of Pain Associated With Fibromyalgia
Actual Study Start Date
:
Jan 16, 2015
Actual Primary Completion Date
:
Jan 6, 2017
Actual Study Completion Date
:
Jan 12, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants take one each of placebo tablet and capsule, twice daily (BID) |
Drug: Placebo tablet
Placebo tablet for oral use, matching DS-5565 tablet
Other Names:
Drug: Placebo capsule
Placebo capsule for oral use, matching pregabalin capsule
Other Names:
|
| Other: Pregabalin Participants take one pregabalin capsule and one placebo tablet BID |
Drug: Pregabalin
Pregabalin capsule for oral use; 75 mg capsule for one week, then 150 mg capsule
Other Names:
Drug: Placebo tablet
Placebo tablet for oral use, matching DS-5565 tablet
Other Names:
|
| Experimental: DS-5565 15 mg QD Participants take one each of placebo tablet and capsule in the morning and one placebo capsule in the evening with one DS-5565 tablet once daily (QD) |
Drug: DS-5565
DS-5565 15 mg QD or BID; tablet for oral use
Other Names:
Drug: Placebo tablet
Placebo tablet for oral use, matching DS-5565 tablet
Other Names:
Drug: Placebo capsule
Placebo capsule for oral use, matching pregabalin capsule
Other Names:
|
| Experimental: DS-5565 15 mg BID Participants take one placebo capsule with one DS-5565 tablet BID |
Drug: DS-5565
DS-5565 15 mg QD or BID; tablet for oral use
Other Names:
Drug: Placebo capsule
Placebo capsule for oral use, matching pregabalin capsule
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
Average daily pain scores (ADPS) reported by the participant that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale where 0 = no pain to 10 = worst possible pain. Higher scores indicate a worse outcome. For participants with no Week 13 data, the baseline observation was carried forward (BOCF). The mean (multiple imputation estimate) and standard error (multiple imputation) are reported.
Secondary Outcome Measures
- Number of Participants Who Answered "Much Improved or Better" in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. Higher scores indicate worse outcomes. The number of participants with 'much improved or better' status (≤2) is being reported.
- Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) in Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
The total FIQ score is composed of 10 items, with a maximum possible score of 100. The first item contains 11 questions related to physical functioning and are rated on a 4-point Likert-type scale, where 0 indicates 'always' and 3 indicates 'never'. The overall impact items are rated on a 0-7 scale for the number of days that the patient felt well and the number of days they were unable to work (including housework) because of fibromyalgia symptoms. The symptoms items are rated on visual analog scales (0-10 cm), with higher numbers indicated greater symptomatology. Final scores range from 0 (no impairment) to 10 (maximum impairment), where higher scores indicate worse outcome. For this outcome, the change in total FIQ score from baseline is being reported. Negative values indicate improvement from baseline in impairment.
- Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo [Week 13 postdose]
The ADPS responder rate was defined a priori as the proportion of participants who met the clinically relevant reductions (ie, ≥30% and ≥50%) in ADPS at Week 13 (baseline observation carried forward) compared to Baseline.
- Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
MFI is a validated 20-item, self-reported instrument designed to measure fatigue in the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The respondent is asked to mark an 'X' in 1 of 5 boxes arranged linearly where 1 is 'Yes, that is true' and 5 is 'No, that is not true.' Each subscale consists of 4 items, 2 indicative for fatigue and 2 contraindicative. For the indicative questions, a high score indicates a high fatigue level and low scores indicate a low fatigue levels. Conversely, for the contraindicative questions a high score indicates a low fatigue level and a low score indicates a high fatigue level. Overall, respondents are rated on a scale of 0 (no fatigue) to 7 (high fatigue). For this outcome, the change from baseline in MFI-20 general fatigue subscale score is being reported. Negative values indicate an improvement in fatigue.
- Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
The HADS questionnaire is a reliable, widely-used self-assessment scale to assess symptoms of anxiety and depression. The instrument consists of 7 questions related to anxiety and 7 related to depression, each rated on a 4-point scale (score of 0 to 3). Scores for anxiety and depression are independently summed to compute HADS-Anxiety and HADS-Depression subscale scores, with ranges from 0 to 21, where higher scores indicate greater severity.
- Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
The SF-36 is a generic health survey that asks 36 questions to measure functional health and well-being from the patient's point of view. The SF-36 provides scores for 8 health domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) as well as psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores. Each scale is transformed into a 0-100 scale with each question carrying the same weight. The lower the score indicates more disability (ie, worse outcome).
- Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with a scale that ranges from 0 (no problems) to 5 (extreme problems). These 5 dimensions are combined into an overall health utilities index, and an numeric rating scale (100 mm visual analog scale) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health. A summary index with a maximum total score of 1 can be derived from these five dimensions by conversion with a table of scores. The maximum total score of 1 indicates the best health outcome. For this outcome, the change from baseline in total EQ-5D score is being reported. Positive values indicate an improvement in health.
- Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
Pain-associated sleep interference will be assessed using the Average Daily Sleep Interference Score that utilize electronic daily diaries with an 11-point numeric rating scale (NRS) for pain, ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep, unable to sleep). Higher scores indicate worse outcomes.
- Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among Participants Receiving DS-5565, Pregabalin, or Placebo [Week 13 postdose]
The MOS Sleep Scale is a 12-item questionnaire from which the following subscales were derived: sleep disturbance (4 items), quantity of sleep/optimal sleep (1 item), snoring (1 item), awakening due to shortness of breath or due to headache (1 item), sleep adequacy (2 items), and somnolence (3 items). In addition, values for sleep disturbances index (9 items), optimal sleep scale (1 item), and sleep quantity scale (1 item) were determined. Most subscales range from 0 to 100, where higher scores indicate more of the concept begin measured (eg., higher sleep disturbance scores indicate greater sleep disturbances).
- Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
The BPI-SF measures pain severity and interference within the past 24 hours. Items are rated on an 11-point NRS from 0 to 10, where 0 indicates does not interfere and 10 indicates completely interferes. Severity score is the average of the responses to the 4 pain intensity items that assess the Worst/Least/Average pain in the last 24 hours and the Pain Right Now. The individual items being reported (using the same scale as noted above) are Severity, General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life. Percentage relief of treatment pain scale ranges from 100% (complete pain relief) to 0% (no pain relief) and higher percentages indicate better outcome. Interference % is the average of responses for General activity, Mood, Walking ability, Normal work, Relations with other people, Sleep, Enjoyment of life where 0% (no interference) to 100% (completely interferes) and negative (ie. lower) percentages indicate better outcomes.
- Proportion of Days a Rescue Medication Was Used Among Participants Receiving DS-5565, Pregabalin, or Placebo [Week 1 to Week 13 postdose]
Proportion of days with rescue medication intake during the double-blind treatment period equals number of days with rescue medication intake/(date of last study drug administration in the double-blind treatment period) - (date of first study drug administration + 1).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age ≥ 18 years
-
Able to give written informed consent
-
Able to complete subject-reported questionnaires per the investigator's judgment
-
At screening, subjects must meet the 1990 American College of Rheumatology (ACR) criteria for FM, i.e. widespread pain present for at least 3 months and pain in at least 11 of 18 specific tender point sites. In addition, the 2010 ACR criteria must be met:
-
Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5, or WPI 3 to 6 and SS scale score ≥ 9
-
Symptoms have been present at a similar level for at least 3 months
-
The subject does not have a disorder that would otherwise explain the pain
-
ADPS of ≥ 4 on the 11-point numeric rating scale (NRS) over the past 7 days prior to randomization (based on completion of at least 4 daily pain diaries during the 7-day baseline period prior to randomization)
-
Subject must have documented evidence of a fundoscopic examination (with pupil dilation) within 12 months prior to screening or at screening.
-
Women of child-bearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during the study and for 4 weeks after study completion.
Exclusion Criteria:
-
Clinically significant unstable neurologic, psychiatric, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (e.g. severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) or any other concurrent disease within 12 months prior to screening that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability
-
Anticipation of initiation or significant change to normal daily exercise routines or need for ongoing use of concomitant medications or non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety
-
Unable to undergo pre-study washout of prohibited concomitant medications
-
Subjects who are at risk of suicide as defined by their responses to the Columbia-Suicide Severity Rating Scale (C-SSRS) or in the opinion of the investigator. Note: Patients answering "yes" to any of the C-SSRS questions at screening must be excluded. Such patients should be referred immediately to a mental health professional for appropriate evaluation.
-
Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study.
-
Any diagnosis of lifetime bipolar disorder or psychotic disorder
-
Subjects with pain due to other conditions (e.g. diabetic peripheral neuropathic pain or post-herpetic neuralgia) that in the opinion of the investigator, would confound assessment or self-evaluation of the pain associated with FM.
-
Subjects with pain due to any widespread inflammatory musculoskeletal disorder (e.g. rheumatoid arthritis, lupus) or widespread rheumatic disease other than FM.
-
Abuse or dependence of prescription medications, street drugs, or alcohol within the last 1 year
-
Any history of a malignancy other than basal cell carcinoma within the past 5 years
-
A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months
-
Pregnancy or breast-feeding, or intent to become pregnant during the study period
-
Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents.
-
Known hypersensitivity to alpha2-delta (α2δ) ligands or other components of the study medications. Note: Prior exposure to DS-5565 is allowed, as long as hypersensitivity to DS-5565 was not observed.
-
Subjects who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the investigator to be unlikely to complete the study.
-
Abnormal investigative tests (i.e. electrocardiograms [ECGs]) and laboratory values judged by the investigator to be clinically significant at screening, with particular focus on: a. Abnormal renal function defined as calculated creatinine clearance (CrCl) < 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen> 1.5 × upper limit of normal (ULN); creatine kinase > 3.0 × ULN; serum creatinine > 1.6 mg/dL (> 141.4 μmol/L); b. Abnormal liver function defined as aspartate aminotransferase (AST) > 2.0 × ULN, alanine aminotransferase (ALT) > 2.0 × ULN; alkaline phosphatase > 1.5 × ULN; total bilirubin> 1.2 × ULN. If a subject has total bilirubin > 1.2 ULN, unconjugated and conjugated bilirubin fractions should be analyzed and only subjects documented to have Gilbert's syndrome may be enrolled.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | 35242 | |
| 2 | Huntsville | Alabama | United States | ||
| 3 | Phoenix | Arizona | United States | 85020 | |
| 4 | Scottsdale | Arizona | United States | ||
| 5 | Tempe | Arizona | United States | ||
| 6 | Tucson | Arizona | United States | ||
| 7 | Anaheim | California | United States | ||
| 8 | Covina | California | United States | 91723 | |
| 9 | El Cajon | California | United States | 92020 | |
| 10 | Encino | California | United States | ||
| 11 | Huntington Beach | California | United States | 92646 | |
| 12 | Lakewood | California | United States | 90712 | |
| 13 | Lomita | California | United States | 90717 | |
| 14 | Los Angeles | California | United States | ||
| 15 | National City | California | United States | 91950 | |
| 16 | Northridge | California | United States | 91324 | |
| 17 | Oceanside | California | United States | ||
| 18 | Sacramento | California | United States | ||
| 19 | Upland | California | United States | 91786 | |
| 20 | Walnut Creek | California | United States | ||
| 21 | Boca Raton | Florida | United States | 33486 | |
| 22 | DeLand | Florida | United States | 32720 | |
| 23 | Edgewater | Florida | United States | 32132 | |
| 24 | Fort Lauderdale | Florida | United States | ||
| 25 | Fort Myers | Florida | United States | ||
| 26 | Hialeah | Florida | United States | 33016 | |
| 27 | Largo | Florida | United States | 33774 | |
| 28 | Lauderdale Lakes | Florida | United States | 33319 | |
| 29 | Maitland | Florida | United States | ||
| 30 | Miami | Florida | United States | ||
| 31 | Orlando | Florida | United States | 32807 | |
| 32 | Sunrise | Florida | United States | ||
| 33 | Tamarac | Florida | United States | ||
| 34 | Tampa | Florida | United States | ||
| 35 | Vero Beach | Florida | United States | 32960 | |
| 36 | West Palm Beach | Florida | United States | ||
| 37 | Winter Haven | Florida | United States | ||
| 38 | Winter Park | Florida | United States | ||
| 39 | Dawsonville | Georgia | United States | ||
| 40 | Marietta | Georgia | United States | 30060 | |
| 41 | Smyrna | Georgia | United States | ||
| 42 | Chicago | Illinois | United States | ||
| 43 | Evansville | Indiana | United States | ||
| 44 | Granger | Indiana | United States | ||
| 45 | Overland Park | Kansas | United States | ||
| 46 | Owensboro | Kentucky | United States | 423303 | |
| 47 | Lake Charles | Louisiana | United States | ||
| 48 | New Orleans | Louisiana | United States | 70119 | |
| 49 | Frederick | Maryland | United States | ||
| 50 | Brockton | Massachusetts | United States | ||
| 51 | North Dartmouth | Massachusetts | United States | ||
| 52 | Ann Arbor | Michigan | United States | 48104 | |
| 53 | Ann Arbor | Michigan | United States | ||
| 54 | Lansing | Michigan | United States | ||
| 55 | Rochester Hills | Michigan | United States | ||
| 56 | Florissant | Missouri | United States | ||
| 57 | Hazelwood | Missouri | United States | ||
| 58 | O'Fallon | Missouri | United States | ||
| 59 | Bellevue | Nebraska | United States | ||
| 60 | Newington | New Hampshire | United States | ||
| 61 | Albuquerque | New Mexico | United States | ||
| 62 | Brooklyn | New York | United States | 11230 | |
| 63 | Cedarhurst | New York | United States | ||
| 64 | Rochester | New York | United States | ||
| 65 | Charlotte | North Carolina | United States | ||
| 66 | Raleigh | North Carolina | United States | ||
| 67 | Winston-Salem | North Carolina | United States | ||
| 68 | Minot | North Dakota | United States | 58701 | |
| 69 | Cincinnati | Ohio | United States | ||
| 70 | Columbus | Ohio | United States | ||
| 71 | Dayton | Ohio | United States | ||
| 72 | Middleburg Heights | Ohio | United States | 44130 | |
| 73 | Oklahoma City | Oklahoma | United States | ||
| 74 | Portland | Oregon | United States | ||
| 75 | Altoona | Pennsylvania | United States | ||
| 76 | Media | Pennsylvania | United States | ||
| 77 | Wyomissing | Pennsylvania | United States | ||
| 78 | Greenville | South Carolina | United States | ||
| 79 | Mount Pleasant | South Carolina | United States | ||
| 80 | Chattanooga | Tennessee | United States | 37421 | |
| 81 | Franklin | Tennessee | United States | 37064 | |
| 82 | Knoxville | Tennessee | United States | 37912 | |
| 83 | Memphis | Tennessee | United States | ||
| 84 | Austin | Texas | United States | 78756 | |
| 85 | Houston | Texas | United States | 77024 | |
| 86 | Lake Jackson | Texas | United States | ||
| 87 | San Antonio | Texas | United States | ||
| 88 | Norfolk | Virginia | United States | ||
| 89 | Richmond | Virginia | United States | 23235 | |
| 90 | Bellevue | Washington | United States | 98007 | |
| 91 | Richland | Washington | United States | 99352 | |
| 92 | Caba | Buenos Aires | Argentina | ||
| 93 | La Plata | Buenos Aires | Argentina | ||
| 94 | Lanús | Buenos Aires | Argentina | ||
| 95 | Mar Del Plata | Buenos Aires | Argentina | ||
| 96 | Quilmes | Buenos Aires | Argentina | ||
| 97 | San Fernando | Buenos Aires | Argentina | ||
| 98 | Rosario | Santa FE | Argentina | ||
| 99 | Cordoba | Argentina | |||
| 100 | San Miguel de Tucuman | Argentina | |||
| 101 | Santa Fe | Argentina | |||
| 102 | Klagenfurt | Austria | |||
| 103 | Senftenberg | Austria | 3541 | ||
| 104 | Vienna | Austria | 1090 | ||
| 105 | Minsk | Belarus | |||
| 106 | Vitebsk | Belarus | |||
| 107 | Brussels | Belgium | |||
| 108 | Edegem | Belgium | |||
| 109 | Gozee | Belgium | |||
| 110 | Oostham | Belgium | |||
| 111 | Antofagasta | Chile | |||
| 112 | Providencia | Chile | |||
| 113 | Puerto Varas | Chile | |||
| 114 | Vina Del Mar | Chile | |||
| 115 | Barranquilla | Colombia | |||
| 116 | Bogota | Colombia | |||
| 117 | Haifa | Israel | |||
| 118 | Kfar Saba | Israel | |||
| 119 | Ramat Gan | Israel | |||
| 120 | Tel-aviv | Israel | |||
| 121 | Cuautitlán Izcalli | Mexico | |||
| 122 | Durango | Mexico | |||
| 123 | Guadalajara | Mexico | |||
| 124 | Leon | Mexico | |||
| 125 | Mexico City | Mexico | |||
| 126 | Elblag | Poland | |||
| 127 | Gdansk | Poland | |||
| 128 | Katowice | Poland | |||
| 129 | Kraków | Poland | |||
| 130 | Lublin | Poland | |||
| 131 | Nadarzyn | Poland | |||
| 132 | Nowa Sol | Poland | |||
| 133 | Torun | Poland | |||
| 134 | Tychy | Poland | |||
| 135 | Warsaw | Poland | |||
| 136 | Aveiro | Portugal | |||
| 137 | Braga | Portugal | |||
| 138 | Guimaraes | Portugal | |||
| 139 | Lisboa | Portugal | |||
| 140 | Ponte de Lima | Portugal | |||
| 141 | Porto | Portugal | |||
| 142 | Vila Nova de Gaia | Portugal | |||
| 143 | Ljubljana | Slovenia | |||
| 144 | Slovenj Gradec | Slovenia | |||
| 145 | Alicante | Spain | |||
| 146 | Barcelona | Spain | |||
| 147 | Elche | Spain | |||
| 148 | Granada | Spain | |||
| 149 | Guadalajara | Spain | |||
| 150 | Madrid | Spain | |||
| 151 | Santiago de Compostela | Spain | |||
| 152 | Sevilla | Spain | |||
| 153 | Geneva | Switzerland | |||
| 154 | St. Gallen | Switzerland |
Sponsors and Collaborators
- Daiichi Sankyo, Inc.
- Syneos Health
Investigators
- Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier:
NCT02187471
Other Study ID Numbers:
- DS5565-A-E310
- 2013-005162-20
First Posted:
Jul 11, 2014
Last Update Posted:
Nov 9, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Daiichi Sankyo, Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 2526 participants who met all inclusion criteria and no exclusion criteria were enrolled from 16 Jan 2015 to 12 Jan 2017 at 182 sites. Of the 2526 participants enrolled, 1301 were randomized to treatment. |
|---|---|
| Pre-assignment Detail | Eligible participants were randomized 1:1:1:1 to either DS-5565 15 mg every day (QD) given orally, DS-5565 15 mg twice daily (BID) given orally, placebo given orally as pregabalin placebo and DS-5565 placebo BID, or pregabalin 150 mg BID. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Period Title: Overall Study | ||||
| STARTED | 325 | 324 | 326 | 326 |
| COMPLETED | 249 | 242 | 240 | 246 |
| NOT COMPLETED | 76 | 82 | 86 | 80 |
Baseline Characteristics
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. | Total of all reporting groups |
| Overall Participants | 325 | 324 | 326 | 326 | 1301 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
296
91.1%
|
294
90.7%
|
294
90.2%
|
290
89%
|
1174
90.2%
|
| >=65 years |
29
8.9%
|
30
9.3%
|
32
9.8%
|
36
11%
|
127
9.8%
|
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
48.9
(11.16)
|
49.9
(12.02)
|
50.1
(11.22)
|
49.0
(12.03)
|
49.5
(11.62)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
303
93.2%
|
302
93.2%
|
302
92.6%
|
296
90.8%
|
1203
92.5%
|
| Male |
22
6.8%
|
22
6.8%
|
24
7.4%
|
30
9.2%
|
98
7.5%
|
| Region of Enrollment (participants) [Number] | |||||
| Colombia |
0
0%
|
0
0%
|
1
0.3%
|
0
0%
|
1
0.1%
|
| Argentina |
25
7.7%
|
25
7.7%
|
19
5.8%
|
19
5.8%
|
88
6.8%
|
| United States |
190
58.5%
|
190
58.6%
|
190
58.3%
|
190
58.3%
|
760
58.4%
|
| Belarus |
5
1.5%
|
2
0.6%
|
2
0.6%
|
3
0.9%
|
12
0.9%
|
| Portugal |
8
2.5%
|
8
2.5%
|
1
0.3%
|
5
1.5%
|
22
1.7%
|
| Switzerland |
0
0%
|
0
0%
|
1
0.3%
|
0
0%
|
1
0.1%
|
| Spain |
25
7.7%
|
25
7.7%
|
27
8.3%
|
24
7.4%
|
101
7.8%
|
| Austria |
4
1.2%
|
4
1.2%
|
10
3.1%
|
11
3.4%
|
29
2.2%
|
| Belgium |
5
1.5%
|
5
1.5%
|
3
0.9%
|
2
0.6%
|
15
1.2%
|
| Poland |
20
6.2%
|
21
6.5%
|
23
7.1%
|
22
6.7%
|
86
6.6%
|
| Mexico |
9
2.8%
|
4
1.2%
|
9
2.8%
|
7
2.1%
|
29
2.2%
|
| Slovenia |
4
1.2%
|
2
0.6%
|
4
1.2%
|
1
0.3%
|
11
0.8%
|
| Chile |
7
2.2%
|
11
3.4%
|
12
3.7%
|
15
4.6%
|
45
3.5%
|
| Russia |
7
2.2%
|
7
2.2%
|
6
1.8%
|
7
2.1%
|
27
2.1%
|
| Ukraine |
16
4.9%
|
20
6.2%
|
18
5.5%
|
20
6.1%
|
74
5.7%
|
Outcome Measures
| Title | Change From Baseline to Week 13 in Average Daily Pain Score (ADPS) Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | Average daily pain scores (ADPS) reported by the participant that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale where 0 = no pain to 10 = worst possible pain. Higher scores indicate a worse outcome. For participants with no Week 13 data, the baseline observation was carried forward (BOCF). The mean (multiple imputation estimate) and standard error (multiple imputation) are reported. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 323 | 319 | 324 | 322 |
| Mean (Standard Error) [units on a scale] |
-1.90
(0.135)
|
-2.64
(0.137)
|
-2.04
(0.138)
|
-2.30
(0.136)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4601 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.14 | |
| Confidence Interval |
(2-Sided) 95% -0.52 to 0.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.191 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0350 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -0.77 to -0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.190 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.74 | |
| Confidence Interval |
(2-Sided) 95% -1.12 to -0.37 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.191 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0019 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.60 | |
| Confidence Interval |
(2-Sided) 95% 0.22 to 0.98 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.193 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0761 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.34 | |
| Confidence Interval |
(2-Sided) 95% -0.04 to 0.72 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.192 |
|
| Estimation Comments | ||
| Title | Number of Participants Who Answered "Much Improved or Better" in Patient Global Impression of Change at Week 13 Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. Higher scores indicate worse outcomes. The number of participants with 'much improved or better' status (≤2) is being reported. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 319 | 324 | 323 |
| Count of Participants [Participants] |
88
27.1%
|
145
44.8%
|
127
39%
|
134
41.1%
|
| Title | Change From Baseline to Week 13 in Average Score on the Fibromyalgia Index Questionnaire (FIQ) in Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The total FIQ score is composed of 10 items, with a maximum possible score of 100. The first item contains 11 questions related to physical functioning and are rated on a 4-point Likert-type scale, where 0 indicates 'always' and 3 indicates 'never'. The overall impact items are rated on a 0-7 scale for the number of days that the patient felt well and the number of days they were unable to work (including housework) because of fibromyalgia symptoms. The symptoms items are rated on visual analog scales (0-10 cm), with higher numbers indicated greater symptomatology. Final scores range from 0 (no impairment) to 10 (maximum impairment), where higher scores indicate worse outcome. For this outcome, the change in total FIQ score from baseline is being reported. Negative values indicate improvement from baseline in impairment. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 322 | 318 | 323 | 320 |
| Mean (Standard Error) [units on a scale] |
-15.02
(1.198)
|
-19.42
(1.222)
|
-16.61
(1.215)
|
-20.44
(1.209)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3407 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.59 | |
| Confidence Interval |
(2-Sided) 95% -4.86 to 1.68 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.670 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0012 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.42 | |
| Confidence Interval |
(2-Sided) 95% -8.69 to -2.15 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.669 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0083 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -4.39 | |
| Confidence Interval |
(2-Sided) 95% -7.66 to -1.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.665 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0946 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.80 | |
| Confidence Interval |
(2-Sided) 95% -0.48 to 6.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.677 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5384 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.03 | |
| Confidence Interval |
(2-Sided) 95% -4.30 to 2.24 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.669 |
|
| Estimation Comments | ||
| Title | Number of Participants Classified As Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The ADPS responder rate was defined a priori as the proportion of participants who met the clinically relevant reductions (ie, ≥30% and ≥50%) in ADPS at Week 13 (baseline observation carried forward) compared to Baseline. |
| Time Frame | Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 319 | 324 | 323 |
| 30% Responders |
122
37.5%
|
144
44.4%
|
121
37.1%
|
125
38.3%
|
| 50% Responders |
68
20.9%
|
95
29.3%
|
77
23.6%
|
89
27.3%
|
| Title | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | MFI is a validated 20-item, self-reported instrument designed to measure fatigue in the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The respondent is asked to mark an 'X' in 1 of 5 boxes arranged linearly where 1 is 'Yes, that is true' and 5 is 'No, that is not true.' Each subscale consists of 4 items, 2 indicative for fatigue and 2 contraindicative. For the indicative questions, a high score indicates a high fatigue level and low scores indicate a low fatigue levels. Conversely, for the contraindicative questions a high score indicates a low fatigue level and a low score indicates a high fatigue level. Overall, respondents are rated on a scale of 0 (no fatigue) to 7 (high fatigue). For this outcome, the change from baseline in MFI-20 general fatigue subscale score is being reported. Negative values indicate an improvement in fatigue. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| MFI-20 was assessed in the modified intent-to-treat population. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 307 | 299 | 301 | 300 |
| Mean (Standard Deviation) [units on a scale] |
-1.6
(3.55)
|
-2.6
(4.00)
|
-2.4
(3.91)
|
-3.4
(4.54)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0030 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to -0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.30 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to -1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.30 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to -0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.30 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3562 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.30 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0862 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.30 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The HADS questionnaire is a reliable, widely-used self-assessment scale to assess symptoms of anxiety and depression. The instrument consists of 7 questions related to anxiety and 7 related to depression, each rated on a 4-point scale (score of 0 to 3). Scores for anxiety and depression are independently summed to compute HADS-Anxiety and HADS-Depression subscale scores, with ranges from 0 to 21, where higher scores indicate greater severity. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed in the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 299 | 324 | 323 |
| Change from baseline at Week 13: Anxiety |
-1.0
(3.58)
|
-0.9
(3.81)
|
-1.0
(3.78)
|
-1.0
(4.10)
|
| Change from baseline at Week 13: Depression |
-0.8
(3.67)
|
-1.0
(4.07)
|
-1.0
(3.80)
|
-1.2
(3.69)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Anxiety: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5183 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least square means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Anxiety: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2669 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares mean |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Anxiety: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4630 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Anxiety: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9280 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Anxiety: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7089 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Depression: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0669 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Depression: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0081 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to -0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Depression: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0867 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Depression: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9066 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of least squares means |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.29 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Depression: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3509 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.29 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in Short Form 36 (SF-36) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The SF-36 is a generic health survey that asks 36 questions to measure functional health and well-being from the patient's point of view. The SF-36 provides scores for 8 health domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) as well as psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores. Each scale is transformed into a 0-100 scale with each question carrying the same weight. The lower the score indicates more disability (ie, worse outcome). |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed in the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 319 | 324 | 323 |
| Change from baseline to Week 13:Physical Component |
3.78
(7.22)
|
6.46
(8.32)
|
5.94
(8.06)
|
6.22
(8.46)
|
| Change from baseline to Week 13: Mental Component |
2.23
(9.54)
|
1.97
(10.53)
|
1.56
(10.19)
|
2.71
(9.67)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Physical Component: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 2.187 | |
| Confidence Interval |
(2-Sided) 95% 0.970 to 3.404 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6203 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Physical Component: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of least squares means |
| Estimated Value | 2.483 | |
| Confidence Interval |
(2-Sided) 95% 1.265 to 3.701 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6209 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Physical Component: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 2.621 | |
| Confidence Interval |
(2-Sided) 95% 1.401 to 3.840 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6215 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Physical Component: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4877 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.434 | |
| Confidence Interval |
(2-Sided) 95% -1.659 to 0.792 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6245 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Physical Component: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8263 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.137 | |
| Confidence Interval |
(2-Sided) 95% -1.364 to 1.089 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6252 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Mental Component: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7567 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.228 | |
| Confidence Interval |
(2-Sided) 95% -1.213 to 1.669 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7345 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Mental Component: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0787 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.7349 | |
| Confidence Interval |
(2-Sided) 95% -0.149 to 2.735 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7349 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Mental Component: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3516 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.7358 | |
| Confidence Interval |
(2-Sided) 95% -0.758 to 2.129 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7358 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Mental Component: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5344 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.458 | |
| Confidence Interval |
(2-Sided) 95% -1.905 to 0.988 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7372 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Mental Component: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4107 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.607 | |
| Confidence Interval |
(2-Sided) 95% -0.840 to 2.055 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.7379 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with a scale that ranges from 0 (no problems) to 5 (extreme problems). These 5 dimensions are combined into an overall health utilities index, and an numeric rating scale (100 mm visual analog scale) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health. A summary index with a maximum total score of 1 can be derived from these five dimensions by conversion with a table of scores. The maximum total score of 1 indicates the best health outcome. For this outcome, the change from baseline in total EQ-5D score is being reported. Positive values indicate an improvement in health. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed in the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 307 | 299 | 301 | 300 |
| Mean (Standard Deviation) [units on a scale] |
0.09
(0.19)
|
0.1274
(0.20)
|
0.10
(0.19)
|
0.11
(0.21)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1394 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0203 | |
| Confidence Interval |
(2-Sided) 95% -0.0066 to 0.0471 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01369 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1237 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0211 | |
| Confidence Interval |
(2-Sided) 95% -0.0058 to 0.0480 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01369 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0049 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0386 | |
| Confidence Interval |
(2-Sided) 95% 0.0117 to 0.0655 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01371 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1824 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0184 | |
| Confidence Interval |
(2-Sided) 95% -0.0454 to 0.0086 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01378 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2036 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0175 | |
| Confidence Interval |
(2-Sided) 95% -0.0446 to 0.0095 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01378 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in Average Daily Sleep Interference Score (ADSIS) Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | Pain-associated sleep interference will be assessed using the Average Daily Sleep Interference Score that utilize electronic daily diaries with an 11-point numeric rating scale (NRS) for pain, ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep, unable to sleep). Higher scores indicate worse outcomes. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 319 | 324 | 323 |
| Mean (Standard Deviation) [units on a scale] |
-1.76
(0.116)
|
-2.71
(0.116)
|
-2.31
(0.117)
|
-2.64
(0.116)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0006 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.56 | |
| Confidence Interval |
(2-Sided) 95% -0.87 to -0.24 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.162 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.88 | |
| Confidence Interval |
(2-Sided) 95% -1.20 to -0.57 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.160 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.95 | |
| Confidence Interval |
(2-Sided) 95% -1.27 to -0.63 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.161 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0158 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.39 | |
| Confidence Interval |
(2-Sided) 95% 0.07 to 0.71 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.162 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6819 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.07 | |
| Confidence Interval |
(2-Sided) 95% -0.25 to 0.38 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.161 |
|
| Estimation Comments | ||
| Title | Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The MOS Sleep Scale is a 12-item questionnaire from which the following subscales were derived: sleep disturbance (4 items), quantity of sleep/optimal sleep (1 item), snoring (1 item), awakening due to shortness of breath or due to headache (1 item), sleep adequacy (2 items), and somnolence (3 items). In addition, values for sleep disturbances index (9 items), optimal sleep scale (1 item), and sleep quantity scale (1 item) were determined. Most subscales range from 0 to 100, where higher scores indicate more of the concept begin measured (eg., higher sleep disturbance scores indicate greater sleep disturbances). |
| Time Frame | Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 319 | 324 | 323 |
| Count of Participants [Participants] |
78
24%
|
107
33%
|
102
31.3%
|
119
36.5%
|
| Title | Change From Baseline at Week 13 in the Brief Pain Inventory Short Form (BPI-SF) Measure Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The BPI-SF measures pain severity and interference within the past 24 hours. Items are rated on an 11-point NRS from 0 to 10, where 0 indicates does not interfere and 10 indicates completely interferes. Severity score is the average of the responses to the 4 pain intensity items that assess the Worst/Least/Average pain in the last 24 hours and the Pain Right Now. The individual items being reported (using the same scale as noted above) are Severity, General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life. Percentage relief of treatment pain scale ranges from 100% (complete pain relief) to 0% (no pain relief) and higher percentages indicate better outcome. Interference % is the average of responses for General activity, Mood, Walking ability, Normal work, Relations with other people, Sleep, Enjoyment of life where 0% (no interference) to 100% (completely interferes) and negative (ie. lower) percentages indicate better outcomes. |
| Time Frame | Baseline up to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 319 | 324 | 323 |
| Worst pain |
-1.9
(2.26)
|
-2.7
(2.78)
|
-2.2
(2.48)
|
-2.7
(2.52)
|
| Least pain |
-1.5
(2.48)
|
-2.3
(2.58)
|
-2.0
(2.43)
|
-2.1
(2.53)
|
| Average pain |
-1.5
(2.11)
|
-2.3
(2.27)
|
-2.0
(2.28)
|
-2.3
(2.39)
|
| Pain right now |
-2.1
(2.44)
|
-2.8
(2.74)
|
-2.5
(2.50)
|
-2.9
(2.72)
|
| Severity score |
-1.75
(2.05)
|
-2.55
(2.35)
|
-2.16
(2.13)
|
-2.51
(2.26)
|
| Percentage of relief by treatment of pain |
23.1
(31.93)
|
32.6
(35.39)
|
31.8
(32.28)
|
36.0
(34.68)
|
| Interference (%) |
-16.19
(21.83)
|
-23.55
(23.60)
|
-21.66
(22.29)
|
-25.97
(23.38)
|
| General activity |
-1.7
(2.60)
|
-2.5
(2.87)
|
-2.3
(2.69)
|
-2.6
(2.82)
|
| Mood |
-1.6
(2.83)
|
-2.1
(2.92)
|
-1.9
(2.95)
|
-2.4
(2.95)
|
| Walking ability |
-1.4
(2.66)
|
-1.7
(2.96)
|
-1.8
(2.73)
|
-2.1
(2.66)
|
| Normal work |
-1.6
(2.52)
|
-2.3
(2.93)
|
-2.1
(2.63)
|
-2.7
(2.73)
|
| Relations with other people |
-1.3
(2.89)
|
-1.9
(3.03)
|
-1.6
(2.95)
|
-2.0
(2.97)
|
| Sleep |
-2.1
(3.13)
|
-3.6
(3.13)
|
-3.1
(3.06)
|
-3.9
(3.08)
|
| Enjoyment of life |
-1.6
(2.94)
|
-2.4
(3.06)
|
-2.3
(2.95)
|
-2.4
(3.27)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Worst pain: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of least squares means |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to -0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Worst pain: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of least squares means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Worst pain: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to -0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Worst pain: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0030 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% 0.2 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Worst pain: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3351 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Least pain: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to -0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.18 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Least pain: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0782 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.18 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Least pain: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0068 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.18 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Least pain: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0169 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% 0.1 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Least pain: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1481 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Average pain: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to -0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Average pain: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0088 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Average pain: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to -0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Average pain: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0627 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.0 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Average pain: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3064 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Pain right now: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to -0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.20 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Pain right now: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0868 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares mean |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.20 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Pain right now: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to -0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.20 |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Pain right now: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0271 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% 0.1 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.20 |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Pain right now: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6838 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.20 |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Severity score: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.791 | |
| Confidence Interval |
(2-Sided) 95% -1.129 to -0.454 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1720 |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Severity score: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0552 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.330 | |
| Confidence Interval |
(2-Sided) 95% -0.667 to 0.007 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1718 |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Severity score: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.612 | |
| Confidence Interval |
(2-Sided) 95% -0.950 to -0.275 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1718 |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Severity score: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0077 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.462 | |
| Confidence Interval |
(2-Sided) 95% 0.122 to 0.801 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1729 |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Severity score: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3014 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.179 | |
| Confidence Interval |
(2-Sided) 95% -0.161 to 0.518 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1730 |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Relief (%) by treatment of pain: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 9.6 | |
| Confidence Interval |
(2-Sided) 95% 4.9 to 14.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.40 |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Relief (%) by treatment of pain: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 8.5 | |
| Confidence Interval |
(2-Sided) 95% 3.8 to 13.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.39 |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Relief (%) by treatment of pain: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 10.4 | |
| Confidence Interval |
(2-Sided) 95% 5.7 to 15.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.39 |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Relief (%) by treatment of pain: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6449 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -5.8 to 3.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.41 |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Relief (%) by treatment of pain: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7340 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least square means |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 95% -3.9 to 5.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.41 |
|
| Estimation Comments | ||
| Title | Proportion of Days a Rescue Medication Was Used Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | Proportion of days with rescue medication intake during the double-blind treatment period equals number of days with rescue medication intake/(date of last study drug administration in the double-blind treatment period) - (date of first study drug administration + 1). |
| Time Frame | Week 1 to Week 13 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome was assessed using the modified intent-to-treat analysis set. |
| Arm/Group Title | Placebo | Pregabalin | DS-5565 15 mg QD | DS-5565 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. |
| Measure Participants | 324 | 319 | 324 | 323 |
| Mean (Standard Deviation) [proportion of days] |
0.23
(0.32)
|
0.15
(0.25)
|
0.21
(0.31)
|
0.16
(0.26)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4816 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.016 | |
| Confidence Interval |
(2-Sided) 95% -0.060 to 0.028 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0225 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0044 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least square means |
| Estimated Value | -0.064 | |
| Confidence Interval |
(2-Sided) 95% -.109 to -0.020 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0225 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.074 | |
| Confidence Interval |
(2-Sided) 95% -0.119 to -0.030 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0226 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0094 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.059 | |
| Confidence Interval |
(2-Sided) 95% 0.014 to 0.103 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0226 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6527 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.010 | |
| Confidence Interval |
(2-Sided) 95% -0.034 to 0.055 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0226 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after the last dose of study medication, up to 2 years 3 months. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | A TEAE was any adverse event that emerged on or after the first dosing of double-blind study medication and during study treatment up to 4 weeks after the last dose of double-blind study medication (having been absent prior to treatment) or worsened relative to the pre-double-blind treatment state. | |||||||
| Arm/Group Title | Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID | ||||
| Arm/Group Description | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening. | Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening. | Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening. | ||||
All Cause Mortality |
||||||||
| Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/324 (0%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/324 (2.8%) | 2/319 (0.6%) | 5/324 (1.5%) | 5/323 (1.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain upper | 1/324 (0.3%) | 0/319 (0%) | 1/324 (0.3%) | 0/323 (0%) | ||||
| Gastric ulcer haemorrhage | 0/324 (0%) | 0/319 (0%) | 0/324 (0%) | 1/323 (0.3%) | ||||
| General disorders | ||||||||
| Chest pain | 0/324 (0%) | 0/319 (0%) | 1/324 (0.3%) | 0/323 (0%) | ||||
| Infections and infestations | ||||||||
| Pyelonephritis acute | 0/324 (0%) | 0/319 (0%) | 0/324 (0%) | 1/323 (0.3%) | ||||
| Urinary tract infection | 0/324 (0%) | 0/319 (0%) | 0/324 (0%) | 1/323 (0.3%) | ||||
| Wound infection staphylococcal | 0/324 (0%) | 0/319 (0%) | 1/324 (0.3%) | 0/323 (0%) | ||||
| Abdominal wall abscess | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
| Gastroenteritis | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
| Pneumonia | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Animal bite | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
| Investigations | ||||||||
| Hepatic enzyme increased | 0/324 (0%) | 0/319 (0%) | 0/324 (0%) | 1/323 (0.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Musculoskeletal pain | 0/324 (0%) | 0/319 (0%) | 1/324 (0.3%) | 0/323 (0%) | ||||
| Lumbar spinal stenosis | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
| Nervous system disorders | ||||||||
| Uraemic encephalopathy | 0/324 (0%) | 0/319 (0%) | 0/324 (0%) | 1/323 (0.3%) | ||||
| Convulsion | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
| Seizure like phenomena | 0/324 (0%) | 1/319 (0.3%) | 0/324 (0%) | 0/323 (0%) | ||||
| Transient ischaemic attack | 0/324 (0%) | 1/319 (0.3%) | 0/324 (0%) | 0/323 (0%) | ||||
| Psychiatric disorders | ||||||||
| Suicidal ideation | 0/324 (0%) | 0/319 (0%) | 1/324 (0.3%) | 0/323 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Renal failure | 0/324 (0%) | 0/319 (0%) | 0/324 (0%) | 1/323 (0.3%) | ||||
| Nephrolithiasis | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Cervical dysplasia | 1/324 (0.3%) | 0/319 (0%) | 0/324 (0%) | 0/323 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | Pregabalin 150 mg BID | DS-5565 15 mg QD | DS-5565 15 mg BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 171/324 (52.8%) | 289/319 (90.6%) | 258/324 (79.6%) | 247/323 (76.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 11/324 (3.4%) | 18/319 (5.6%) | 25/324 (7.7%) | 20/323 (6.2%) | ||||
| General disorders | ||||||||
| Drug withdrawal syndrome | 10/324 (3.1%) | 12/319 (3.8%) | 15/324 (4.6%) | 21/323 (6.5%) | ||||
| Oedema peripheral | 4/324 (1.2%) | 18/319 (5.6%) | 11/324 (3.4%) | 15/323 (4.6%) | ||||
| Fatigue | 10/324 (3.1%) | 15/319 (4.7%) | 15/324 (4.6%) | 14/323 (4.3%) | ||||
| Infections and infestations | ||||||||
| Urinary tract infection | 14/324 (4.3%) | 10/319 (3.1%) | 20/324 (6.2%) | 16/323 (5%) | ||||
| Nasopharyngitis | 13/324 (4%) | 19/319 (6%) | 13/324 (4%) | 14/323 (4.3%) | ||||
| Investigations | ||||||||
| Weight increased | 22/324 (6.8%) | 49/319 (15.4%) | 26/324 (8%) | 34/323 (10.5%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 11/324 (3.4%) | 11/319 (3.4%) | 18/324 (5.6%) | 7/323 (2.2%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 17/324 (5.2%) | 56/319 (17.6%) | 47/324 (14.5%) | 36/323 (11.1%) | ||||
| Headache | 50/324 (15.4%) | 41/319 (12.9%) | 39/324 (12%) | 31/323 (9.6%) | ||||
| Somnolence | 9/324 (2.8%) | 40/319 (12.5%) | 29/324 (9%) | 39/323 (12.1%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Daiichi Sankyo US Contact for Clinical Trial Results |
|---|---|
| Organization | Daiichi Sankyo, Inc. |
| Phone | 1-908-992-6400 |
| CTRinfo@DSI.com |
Responsible Party:
Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier:
NCT02187471
Other Study ID Numbers:
- DS5565-A-E310
- 2013-005162-20
First Posted:
Jul 11, 2014
Last Update Posted:
Nov 9, 2020
Last Verified:
Nov 1, 2020