Treatment of Pain Associated With Fibromyalgia
Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02146430
Collaborator
Syneos Health (Other)
1,293
165
4
20.6
7.8
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 subjects receiving either dose of DS-5565 versus placebo. Weekly ADPS is based on daily pain scores reported by the participant 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
:
1293 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
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
:
Oct 27, 2014
Actual Primary Completion Date
:
Jul 14, 2016
Actual Study Completion Date
:
Jul 14, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: DS-5565 QD Participants take one each of placebo tablet and capsule in the morning, and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening |
Drug: DS-5565
DS-5565 15 mg tablet for oral administration
Other Names:
Drug: Placebo tablet
Placebo tablet (matching DS-5565) for oral administration
Other Names:
Drug: Placebo capsule
Placebo capsule (matching pregabalin) for oral administration
Other Names:
|
| Experimental: DS-5565 BID Participants take one DS-5565 tablet and one placebo capsule, twice daily (BID) |
Drug: DS-5565
DS-5565 15 mg tablet for oral administration
Other Names:
Drug: Placebo capsule
Placebo capsule (matching pregabalin) for oral administration
Other Names:
|
| Active Comparator: Pregabalin Participants take one pregabalin capsule and one placebo tablet BID |
Drug: Pregabalin
Pregabalin 150 mg capsule for oral administration
Other Names:
Drug: Placebo tablet
Placebo tablet (matching DS-5565) for oral administration
Other Names:
|
| Placebo Comparator: Placebo Participants take one each of placebo tablet and capsule BID |
Drug: Placebo tablet
Placebo tablet (matching DS-5565) for oral administration
Other Names:
Drug: Placebo capsule
Placebo capsule (matching pregabalin) for oral administration
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Weekly Average Daily Pain Score (ADPS) at Week 13 in Participants Receiving DS-5565, Pregabalin, 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 (PGIC) at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up 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 in Fibromyalgia Index Questionnaire (FIQ) Total Score From Baseline to Week 13 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. 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 Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo [Week 13 postdose]
The number of participants with at least a 30% or 50% reduction in average daily pain score (ADPS) at Week 13 is reported.
- Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in 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) in 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 (no anxiety/depression) to 21 (most severe anxiety/depression).
- Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up to Week 13 postdose]
The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 scale ranges from 0 to 100 where lower scores indicate more disability (worse health) and higher scores represent less disability (better health). The physical component summary (PCS) and mental component summary (MCS) scores are reported.
- Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in 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 a 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 in Participants Receiving DS-5565, Pregabalin, or Placebo [Baseline up Week 13 postdose]
Pain-associated sleep interference was assessed using electronic daily diaries using 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). ADSIS is the mean value of all available recordings of the respective week.
- Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale In 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 to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in 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 participant-reported questionnaires per the investigator's judgment
-
At screening, participants must meet the 1990 American College of Rheumatology (ACR) criteria for fibromyalgia (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 questions about active suicidal ideation/intent/behaviors occurring within the past 12 months must be excluded (C-SSRS Suicide Ideation section - Questions 3, 4, or 5; C-SSRS Suicidal Behavior section, any of the suicide behaviors questions). 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
-
Participants 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.
-
Participants 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
-
Participant 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.
-
Participants 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 participants documented to have Gilbert's syndrome may be enrolled.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Glendale | Arizona | United States | ||
| 2 | Phoenix | Arizona | United States | ||
| 3 | Anaheim | California | United States | ||
| 4 | Beverly Hills | California | United States | 90211 | |
| 5 | Los Alamitos | California | United States | 90720 | |
| 6 | Newport Beach | California | United States | ||
| 7 | Oakland | California | United States | ||
| 8 | Rancho Mirage | California | United States | ||
| 9 | Roseville | California | United States | 95661 | |
| 10 | San Diego | California | United States | 92108 | |
| 11 | Sherman Oaks | California | United States | 91403 | |
| 12 | Torrance | California | United States | 90502 | |
| 13 | Tustin | California | United States | 92780 | |
| 14 | Colorado Springs | Colorado | United States | 80916 | |
| 15 | Denver | Colorado | United States | 80209 | |
| 16 | Cromwell | Connecticut | United States | ||
| 17 | Danbury | Connecticut | United States | ||
| 18 | Boynton Beach | Florida | United States | 33472 | |
| 19 | Bradenton | Florida | United States | ||
| 20 | Brooksville | Florida | United States | ||
| 21 | Coral Springs | Florida | United States | ||
| 22 | Gainesville | Florida | United States | ||
| 23 | Jacksonville | Florida | United States | ||
| 24 | Lakeland | Florida | United States | ||
| 25 | Miami | Florida | United States | ||
| 26 | Ocala | Florida | United States | ||
| 27 | Orlando | Florida | United States | ||
| 28 | Port Orange | Florida | United States | 32129 | |
| 29 | Royal Palm Beach | Florida | United States | ||
| 30 | Saint Petersburg | Florida | United States | 33707 | |
| 31 | Sanford | Florida | United States | ||
| 32 | Savannah | Georgia | United States | 31406 | |
| 33 | Chicago | Illinois | United States | 60634 | |
| 34 | Elwood | Indiana | United States | 46036 | |
| 35 | Indianapolis | Indiana | United States | ||
| 36 | Newton | Kansas | United States | 67114 | |
| 37 | Wichita | Kansas | United States | ||
| 38 | Wheaton | Maryland | United States | 20902 | |
| 39 | Boston | Massachusetts | United States | 02131 | |
| 40 | Fall River | Massachusetts | United States | ||
| 41 | Methuen | Massachusetts | United States | ||
| 42 | New Bedford | Massachusetts | United States | ||
| 43 | Southfield | Michigan | United States | 48034 | |
| 44 | Biloxi | Mississippi | United States | 39531 | |
| 45 | Hattiesburg | Mississippi | United States | ||
| 46 | Kansas City | Missouri | United States | ||
| 47 | Saint Louis | Missouri | United States | 63141 | |
| 48 | Springfield | Missouri | United States | ||
| 49 | Omaha | Nebraska | United States | 68114 | |
| 50 | Las Vegas | Nevada | United States | 89102 | |
| 51 | Berlin | New Jersey | United States | 08009 | |
| 52 | Princeton | New Jersey | United States | ||
| 53 | Stratford | New Jersey | United States | 08084 | |
| 54 | West Long Branch | New Jersey | United States | ||
| 55 | Hartsdale | New York | United States | 10530 | |
| 56 | New York | New York | United States | 10168 | |
| 57 | Valley Stream | New York | United States | ||
| 58 | Williamsville | New York | United States | 14221 | |
| 59 | Charlotte | North Carolina | United States | ||
| 60 | Durham | North Carolina | United States | ||
| 61 | Greensboro | North Carolina | United States | 27410 | |
| 62 | High Point | North Carolina | United States | 27262 | |
| 63 | Raleigh | North Carolina | United States | ||
| 64 | Winston-Salem | North Carolina | United States | ||
| 65 | Cincinnati | Ohio | United States | ||
| 66 | Middleburg Heights | Ohio | United States | ||
| 67 | Toledo | Ohio | United States | 43623 | |
| 68 | Oklahoma City | Oklahoma | United States | ||
| 69 | Medford | Oregon | United States | ||
| 70 | Allentown | Pennsylvania | United States | 18104 | |
| 71 | Mechanicsburg | Pennsylvania | United States | ||
| 72 | Philadelphia | Pennsylvania | United States | 19152 | |
| 73 | Anderson | South Carolina | United States | ||
| 74 | Fountain Inn | South Carolina | United States | ||
| 75 | Greenville | South Carolina | United States | 29601 | |
| 76 | Summerville | South Carolina | United States | 29485 | |
| 77 | Dakota Dunes | South Dakota | United States | 57049 | |
| 78 | Tullahoma | Tennessee | United States | ||
| 79 | Allen | Texas | United States | 75013 | |
| 80 | Austin | Texas | United States | 78731 | |
| 81 | Carrollton | Texas | United States | 75007 | |
| 82 | Dallas | Texas | United States | 75230 | |
| 83 | DeSoto | Texas | United States | ||
| 84 | Houston | Texas | United States | 77079 | |
| 85 | Lubbock | Texas | United States | ||
| 86 | Mesquite | Texas | United States | ||
| 87 | Plano | Texas | United States | ||
| 88 | Richardson | Texas | United States | 75080 | |
| 89 | Sugar Land | Texas | United States | ||
| 90 | Bountiful | Utah | United States | 84010 | |
| 91 | Seattle | Washington | United States | ||
| 92 | Morgantown | West Virginia | United States | ||
| 93 | Burlington | Canada | |||
| 94 | Edmonton | Canada | |||
| 95 | Kentville | Canada | |||
| 96 | Kitchener | Canada | N2M 5N6 | ||
| 97 | London | Canada | N5W 6A2 | ||
| 98 | Markham | Canada | L3R 9W9 | ||
| 99 | Mississauga | Canada | L5B 4M4 | ||
| 100 | Newmarket | Canada | L3Y 5G8 | ||
| 101 | Oshawa | Canada | L1H 1G6 | ||
| 102 | Penticton | Canada | |||
| 103 | Pointe-Claire | Canada | H9R 3J1 | ||
| 104 | Sarnia | Canada | N7T 4X3 | ||
| 105 | Sherbrooke | Canada | |||
| 106 | Toronto | Canada | M3J 2C5 | ||
| 107 | Vancouver | Canada | |||
| 108 | Winnipeg | Canada | |||
| 109 | Choceň | Czechia | |||
| 110 | Prague | Czechia | |||
| 111 | Rychnov nad Kneznou | Czechia | |||
| 112 | Říčany | Czechia | |||
| 113 | Aalborg | Denmark | |||
| 114 | Odense | Denmark | |||
| 115 | Hyvinkää | Finland | |||
| 116 | Kokkola | Finland | |||
| 117 | Amiens | France | |||
| 118 | Cubray | France | |||
| 119 | Elancourt | France | |||
| 120 | Grenoble | France | |||
| 121 | Paris | France | |||
| 122 | Saint-Étienne | France | |||
| 123 | Toulouse | France | |||
| 124 | Bad Doberan | Germany | |||
| 125 | Berlin | Germany | |||
| 126 | Böhlen | Germany | |||
| 127 | Chemnitz | Germany | |||
| 128 | Cottbus | Germany | |||
| 129 | Dresden | Germany | |||
| 130 | Eichstätt | Germany | |||
| 131 | Essen | Germany | |||
| 132 | Fellbach | Germany | |||
| 133 | Frankfurt | Germany | |||
| 134 | Hamburg | Germany | |||
| 135 | Jena | Germany | |||
| 136 | Koeln | Germany | |||
| 137 | Leipzig | Germany | |||
| 138 | Mainz | Germany | |||
| 139 | Marburg | Germany | |||
| 140 | Munich | Germany | |||
| 141 | Mönchengladbach | Germany | |||
| 142 | Rodgau | Germany | |||
| 143 | Stadtroda | Germany | |||
| 144 | Wallerfing | Germany | |||
| 145 | Weinheim | Germany | |||
| 146 | Westerstede | Germany | |||
| 147 | Wiesbaden | Germany | |||
| 148 | Würzburg | Germany | |||
| 149 | Beek | Netherlands | |||
| 150 | Leiden | Netherlands | |||
| 151 | Sneek | Netherlands | |||
| 152 | Hamar | Norway | |||
| 153 | Hønefoss | Norway | |||
| 154 | Kløfta | Norway | |||
| 155 | Lier | Norway | |||
| 156 | Lillehammer | Norway | |||
| 157 | Stavanger | Norway | |||
| 158 | Ålesund | Norway | |||
| 159 | Belgrade | Serbia | |||
| 160 | Kragujevac | Serbia | |||
| 161 | Niš | Serbia | |||
| 162 | Novi Sad | Serbia | |||
| 163 | Borås | Sweden | |||
| 164 | Mölndal | Sweden | |||
| 165 | Stockholm | Sweden |
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:
NCT02146430
Other Study ID Numbers:
- DS5565-A-E309
- 2013-005161-40
First Posted:
May 23, 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 1293 participants who met all inclusion and no exclusion criteria were randomized to treatment at 158 sites in 11 countries from 12 Nov 2014 to 14 Jul 2016. |
|---|---|
| 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 QD | DS-5565 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 | 323 | 323 | 324 | 323 |
| Safety Analysis Set | 318 | 318 | 320 | 320 |
| Modified Intent to Treat Set (mITT) | 318 | 317 | 319 | 319 |
| COMPLETED | 256 | 236 | 242 | 224 |
| NOT COMPLETED | 67 | 87 | 82 | 99 |
Baseline Characteristics
| Arm/Group Title | Placebo | Pregabalin | DS-5565 QD | DS-5565 BID | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo for oral administration matching capsule for DS-5565 and matching tablet for pregabalin | Participants take one pregabalin capsule and one placebo tablet BID | Participants take one each of placebo tablet and capsule in the morning and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening | Participants take one DS-5565 tablet and one placebo capsule BID | Total of all reporting groups |
| Overall Participants | 323 | 323 | 324 | 323 | 1293 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
48.6
(11.76)
|
49.5
(11.53)
|
50.3
(10.88)
|
49.5
(11.77)
|
49.5
(11.49)
|
| Age, Customized (Count of Participants) | |||||
| 18-64 Years |
298
92.3%
|
298
92.3%
|
300
92.6%
|
287
88.9%
|
1183
91.5%
|
| 65-84 Years |
25
7.7%
|
24
7.4%
|
24
7.4%
|
36
11.1%
|
109
8.4%
|
| 85 Years and over |
0
0%
|
1
0.3%
|
0
0%
|
0
0%
|
1
0.1%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
299
92.6%
|
292
90.4%
|
286
88.3%
|
291
90.1%
|
1168
90.3%
|
| Male |
24
7.4%
|
31
9.6%
|
38
11.7%
|
32
9.9%
|
125
9.7%
|
Outcome Measures
| Title | Change From Baseline in Weekly Average Daily Pain Score (ADPS) at Week 13 in Participants Receiving DS-5565, Pregabalin, 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 | 318 | 317 | 319 | 319 |
| Mean (Standard Error) [units on a scale] |
-1.66
(0.132)
|
-1.90
(0.134)
|
-1.97
(0.134)
|
-1.93
(0.136)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1870 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.25 | |
| Confidence Interval |
(2-Sided) 95% -0.61 to 0.12 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.187 |
|
| Estimation Comments | ||
Statistical Analysis 2
| 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 | 0.0944 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.67 to 0.05 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.185 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | 0.1391 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.64 to 0.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.187 |
|
| 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 | 0.7338 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.43 to 0.30 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.187 |
|
| 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 | 0.8705 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.40 to 0.34 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.190 |
|
| Estimation Comments | ||
| Title | Number of Participants Who Answered "Much Improved or Better" in Patient Global Impression of Change (PGIC) at Week 13 in Participants 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 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 | 318 | 317 | 319 | 319 |
| Count of Participants [Participants] |
83
25.7%
|
105
32.5%
|
104
32.1%
|
82
25.4%
|
| Title | Change in Fibromyalgia Index Questionnaire (FIQ) Total Score From Baseline to Week 13 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. 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 pregabalin placebo and DS5565 placebo twice daily (BID). | Participants who received oral pregabalin 150 mg twice daily (BID). | Participants who received oral DS5565 15 mg once daily (QD). | Participants who received DS-5565 15 mg twice daily (BID). |
| Measure Participants | 318 | 317 | 319 | 319 |
| Mean (Standard Deviation) [units on a scale] |
-13.20
(1.173)
|
-16.60
(1.166)
|
-14.48
(1.191)
|
-13.13
(1.199)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0326 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -3.40 | |
| Confidence Interval |
(2-Sided) 95% -6.52 to -0.28 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.592 |
|
| Estimation Comments | ||
Statistical Analysis 2
| 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 | 0.4220 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.28 | |
| Confidence Interval |
(2-Sided) 95% -4.40 to 1.84 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.592 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | 0.9659 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.07 | |
| Confidence Interval |
(2-Sided) 95% -3.10 to 3.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.615 |
|
| 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 | 0.1867 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.12 | |
| Confidence Interval |
(2-Sided) 95% -1.03 to 5.28 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.608 |
|
| 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 | 0.0333 |
| Comments | ||
| Method | Difference of means | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 3.47 | |
| Confidence Interval |
(2-Sided) 95% 0.27 to 6.67 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.631 |
|
| Estimation Comments | ||
| Title | Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The number of participants with at least a 30% or 50% reduction in average daily pain score (ADPS) at Week 13 is reported. |
| 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 pregabalin placebo and DS5565 placebo twice daily (BID). | Participants who received oral pregabalin 150 mg twice daily (BID). | Participants who received oral DS5565 15 mg once daily (QD). | Participants who received DS-5565 15 mg twice daily (BID). |
| Measure Participants | 318 | 317 | 319 | 319 |
| 30% responders |
101
31.3%
|
118
36.5%
|
106
32.7%
|
100
31%
|
| 50% responders |
57
17.6%
|
71
22%
|
71
21.9%
|
57
17.6%
|
| Title | Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in 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 |
|---|
| 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 | 318 | 317 | 319 | 319 |
| Mean (Standard Deviation) [units on a scale] |
-1.9
(3.4)
|
-2.0
(3.82)
|
-2.0
(3.51)
|
-1.6
(3.38)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2474 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| 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 2
| 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 | 0.3347 |
| 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: 0.28 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | 0.3999 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.8 |
|
| 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 | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8435 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.1 | |
| 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 | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0446 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% 0.0 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.28 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in 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 (no anxiety/depression) to 21 (most severe anxiety/depression). |
| 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 pregabalin placebo and DS5565 placebo twice daily (BID). | Participants who received oral pregabalin 150 mg twice daily (BID). | Participants who received oral DS5565 15 mg once daily (QD). | Participants who received DS-5565 15 mg twice daily (BID). |
| Measure Participants | 318 | 317 | 319 | 319 |
| Change from baseline to Week 13: Anxiety |
-1.0
(3.17)
|
-0.8
(3.04)
|
-1.0
(3.25)
|
-1.1
(3.34)
|
| Change from baseline to Week 13: Depression |
-0.8
(3.54)
|
-1.1
(3.23)
|
-0.8
(3.52)
|
-0.6
(3.30)
|
Statistical Analysis 1
| 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 | 0.9775 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of least squares means |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.24 |
|
| Estimation Comments | ||
Statistical Analysis 2
| 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 | 0.6500 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.24 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | 0.6546 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.24 |
|
| 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 | 0.6692 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.24 |
|
| 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 | 0.6737 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.24 |
|
| Estimation Comments | ||
Statistical Analysis 6
| 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 | 0.3888 |
| 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: 0.27 |
|
| Estimation Comments | ||
Statistical Analysis 7
| 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 | 0.9200 |
| 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: 0.27 |
|
| Estimation Comments | ||
Statistical Analysis 8
| 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 | 0.7061 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.27 |
|
| 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 | 0.3337 |
| 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 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.27 |
|
| 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 | 0.2139 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.27 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 scale ranges from 0 to 100 where lower scores indicate more disability (worse health) and higher scores represent less disability (better health). The physical component summary (PCS) and mental component summary (MCS) scores 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 pregabalin placebo and DS5565 placebo twice daily (BID). | Participants who received oral pregabalin 150 mg twice daily (BID). | Participants who received oral DS5565 15 mg once daily (QD). | Participants who received DS-5565 15 mg twice daily (BID). |
| Measure Participants | 318 | 317 | 319 | 319 |
| Change from baseline to Week 13:Physical Component |
8.052
(19.91)
|
9.898
(16.73)
|
8.598
(18.62)
|
7.099
(19.52)
|
| Change from baseline to Week 13: Mental Component |
1.506
(9.25)
|
1.995
(8.59)
|
1.163
(9.32)
|
1.286
(8.85)
|
Statistical Analysis 1
| 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 | 0.1416 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 2.197 | |
| Confidence Interval |
(2-Sided) 95% -0.733 to 5.126 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4933 |
|
| Estimation Comments | ||
Statistical Analysis 2
| 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 | 0.8677 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.249 | |
| Confidence Interval |
(2-Sided) 95% -2.679 to 3.176 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4920 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | 0.5481 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.899 | |
| Confidence Interval |
(2-Sided) 95% -3.834 to 2.036 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4959 |
|
| 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 | 0.1906 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.948 | |
| Confidence Interval |
(2-Sided) 95% -4.866 to 0.971 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4875 |
|
| 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 | 0.0378 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -3.095 | |
| Confidence Interval |
(2-Sided) 95% -6.015 to -0.175 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.4883 |
|
| Estimation Comments | ||
Statistical Analysis 6
| 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 | 0.3337 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.664 | |
| Confidence Interval |
(2-Sided) 95% -0.683 to 2.011 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6865 |
|
| Estimation Comments | ||
Statistical Analysis 7
| 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 | 0.7778 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.194 | |
| Confidence Interval |
(2-Sided) 95% -1.540 to 1.152 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6860 |
|
| Estimation Comments | ||
Statistical Analysis 8
| 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 | 0.8991 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.087 | |
| Confidence Interval |
(2-Sided) 95% -1.437 to 1.262 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6879 |
|
| 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 | 0.2098 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.857 | |
| Confidence Interval |
(2-Sided) 95% -2.198 to 0.483 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6833 |
|
| 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 | 0.2725 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.751 | |
| Confidence Interval |
(2-Sided) 95% -2.093 to 0.591 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6842 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in 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 a 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 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 pregabalin placebo and DS5565 placebo twice daily (BID). | Participants who received oral pregabalin 150 mg twice daily (BID). | Participants who received oral DS5565 15 mg once daily (QD). | Participants who received DS-5565 15 mg twice daily (BID). |
| Measure Participants | 318 | 317 | 319 | 319 |
| Mean (Standard Deviation) [units on a scale] |
0.0779
(0.190)
|
0.0712
(0.182)
|
0.0740
(0.173)
|
0.0696
(0.185)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8923 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0018 | |
| Confidence Interval |
(2-Sided) 95% -0.0243 to 0.0279 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01329 |
|
| Estimation Comments | ||
Statistical Analysis 2
| 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 | 0.8749 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0021 | |
| Confidence Interval |
(2-Sided) 95% -0.0281 to 0.0240 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01327 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | 0.4932 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0091 | |
| Confidence Interval |
(2-Sided) 95% -0.0353 to 0.0170 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01332 |
|
| 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 | 0.7688 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0039 | |
| Confidence Interval |
(2-Sided) 95% -0.0298 to 0.0221 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01323 |
|
| 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 | 0.4099 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0109 | |
| Confidence Interval |
(2-Sided) 95% -0.0369 to 0.0151 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.01326 |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 in Average Daily Sleep Interference in Participants Receiving DS-5565, Pregabalin, or Placebo |
|---|---|
| Description | Pain-associated sleep interference was assessed using electronic daily diaries using 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). ADSIS is the mean value of all available recordings of the respective week. |
| Time Frame | Baseline up 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 pregabalin placebo and DS5565 placebo twice daily (BID). | Participants who received oral pregabalin 150 mg twice daily (BID). | Participants who received oral DS5565 15 mg once daily (QD). | Participants who received DS-5565 15 mg twice daily (BID). |
| Measure Participants | 318 | 317 | 319 | 319 |
| Least Squares Mean (Standard Error) [units on a scale] |
-1.67
(0.120)
|
-2.22
(0.120)
|
-2.30
(0.121)
|
-2.52
(0.121)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.55 | |
| Confidence Interval |
(2-Sided) 95% -0.88 to -0.23 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.166 |
|
| Estimation Comments | ||
Statistical Analysis 2
| 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 | 0.0001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.63 | |
| Confidence Interval |
(2-Sided) 95% -0.96 to -0.31 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.166 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | -0.85 | |
| Confidence Interval |
(2-Sided) 95% -1.17 to -0.52 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.167 |
|
| 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 | 0.6408 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.40 to 0.25 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.167 |
|
| 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 | 0.0786 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -0.62 to 0.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.167 |
|
| Estimation Comments | ||
| Title | Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale In 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 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 | 318 | 317 | 319 | 319 |
| Count of Participants [Participants] |
87
26.9%
|
117
36.2%
|
93
28.7%
|
109
33.7%
|
| Title | Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in 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 pregabalin placebo and DS5565 placebo twice daily (BID). | Participants who received oral pregabalin 150 mg twice daily (BID). | Participants who received oral DS5565 15 mg once daily (QD). | Participants who received DS-5565 15 mg twice daily (BID). |
| Measure Participants | 318 | 317 | 319 | 319 |
| Worst pain |
6.6
(1.41)
|
6.3
(1.50)
|
6.5
(1.48)
|
6.6
(1.47)
|
| Least pain |
-1.2
(0.13)
|
-1.5
(0.13)
|
-1.3
(0.13)
|
-1.3
(0.13)
|
| Average pain |
-1.2
(0.12)
|
-1.5
(0.12)
|
-1.4
(0.12)
|
-1.4
(0.12)
|
| Pain right now |
-1.7
(0.14)
|
-1.9
(0.14)
|
-1.7
(0.14)
|
-1.7
(0.14)
|
| Severity score |
-1.4
(0.12)
|
-1.7
(0.12)
|
-1.5
(0.12)
|
-1.5
(0.12)
|
| Relief (%) by treatment pain |
15.9
(1.78)
|
18.5
(1.74)
|
17.1
(1.77)
|
15.6
(1.76)
|
| Interference (%) |
-14.04
(1.30)
|
-17.91
(1.28)
|
-15.46
(1.30)
|
-15.65
(1.29)
|
| General activity |
-1.5
(0.15)
|
-1.9
(0.15)
|
-1.6
(0.15)
|
-1.6
(0.15)
|
| Mood |
-1.1
(0.16)
|
-1.6
(0.15)
|
-1.3
(0.15)
|
-1.3
(0.15)
|
| Walking ability |
-1.1
(0.16)
|
-1.5
(0.15)
|
-1.1
(0.15)
|
-1.1
(0.15)
|
| Normal work |
-1.5
(0.15)
|
-1.8
(0.15)
|
-1.5
(0.15)
|
-1.5
(0.15)
|
| Relations with other people |
-0.9
(0.15)
|
-1.3
(0.15)
|
-1.3
(0.15)
|
-1.3
(0.15)
|
| Sleep |
-2.1
(0.17)
|
-2.7
(0.17)
|
-2.5
(0.17)
|
-2.6
(0.17)
|
| Enjoyment of life |
-1.6
(0.16)
|
-1.9
(0.16)
|
-1.6
(0.16)
|
-1.5
(0.16)
|
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 | 0.0541 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference of least squares means |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.0 |
|
| 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 | 0.7771 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.3 |
|
| 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 | 0.5488 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 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 | 0.0987 |
| 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 0.7 |
|
| 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 | 0.1840 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.2 | |
| 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 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 | 0.1903 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in 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: 0.18 |
|
| 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 | 0.5787 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.2 |
|
| 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 | 0.5535 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.2 |
|
| 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 | 0.4476 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.18 |
|
| 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 | 0.4737 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.18 |
|
| 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 | 0.0814 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| 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 | 0.3069 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| 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 | 0.3916 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| 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 | 0.4667 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| 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 | 0.3744 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| 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 | 0.2959 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| 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 | 0.9119 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| 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 | 0.9399 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.19 |
|
| 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 BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2455 |
| 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 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 | 0.3311 |
| 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 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 | 0.1233 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.254 | |
| Confidence Interval |
(2-Sided) 95% -0.577 to 0.069 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1647 |
|
| 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 | 0.6610 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.072 | |
| Confidence Interval |
(2-Sided) 95% -0.394 to 0.250 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1643 |
|
| 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 | 0.5514 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.098 | |
| Confidence Interval |
(2-Sided) 95% -0.422 to 0.225 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1649 |
|
| 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 | 0.2673 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.182 | |
| Confidence Interval |
(2-Sided) 95% -0.140 to 0.503 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1638 |
|
| 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 | 0.3439 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.156 | |
| Confidence Interval |
(2-Sided) 95% -0.167 to 0.478 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.1644 |
|
| 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 | 0.2708 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 2.6 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 7.4 |
|
| 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 | 0.6285 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 1.2 | |
| Confidence Interval |
(2-Sided) 95% -3.5 to 5.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.40 |
|
| 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 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9177 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -5.0 to 4.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.41 |
|
| 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 | 0.5334 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.5 | |
| Confidence Interval |
(2-Sided) 95% -6.2 to 3.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.38 |
|
| 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 | 0.2261 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -2.9 | |
| Confidence Interval |
(2-Sided) 95% -7.6 to 1.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.39 |
|
| Estimation Comments | ||
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Interference: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0281 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -3.87 | |
| Confidence Interval |
(2-Sided) 95% -7.32 to -0.42 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.758 |
|
| Estimation Comments | ||
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Interference: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4190 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.42 | |
| Confidence Interval |
(2-Sided) 95% -4.87 to 2.03 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.756 |
|
| Estimation Comments | ||
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Interference: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3622 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -1.61 | |
| Confidence Interval |
(2-Sided) 95% -5.06 to 1.85 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.763 |
|
| Estimation Comments | ||
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Interference: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1623 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 2.45 | |
| Confidence Interval |
(2-Sided) 95% -0.99 to 5.88 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.750 |
|
| Estimation Comments | ||
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Interference: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1978 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 2.26 | |
| Confidence Interval |
(2-Sided) 95% -1.18 to 5.70 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.753 |
|
| Estimation Comments | ||
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | General activity: 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 | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 37
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | General activity: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6993 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 38
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | General activity: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8702 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 39
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | General activity: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1826 |
| 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 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.20 |
|
| Estimation Comments | ||
Statistical Analysis 40
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | General activity: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1206 |
| 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 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 41
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Mood: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0211 |
| 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: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 42
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Mood: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4963 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 43
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Mood: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3031 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 44
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Mood: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1019 |
| 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 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 45
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Mood: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2010 |
| 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 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 46
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Walking ability: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0331 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to -0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 47
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Walking ability: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7478 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 48
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Walking ability: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6940 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 49
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Walking ability: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0690 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.0 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 50
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Walking ability: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0816 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.0 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 51
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Normal work: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1174 |
| 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 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 52
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Normal work: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9250 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 53
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Normal work: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8555 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 54
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Normal work: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0956 |
| 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 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 55
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Normal work: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1659 |
| 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 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 56
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Relations with other people: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0468 |
| 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 -0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 57
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Relations with other people: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1083 |
| 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 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 58
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Relations with other people: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0505 |
| 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 0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 59
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Relations with other people: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6993 |
| 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: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 60
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Relations with other people: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9781 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.21 |
|
| Estimation Comments | ||
Statistical Analysis 61
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Sleep: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0154 |
| 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 -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.23 |
|
| Estimation Comments | ||
Statistical Analysis 62
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Sleep: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0731 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.23 |
|
| Estimation Comments | ||
Statistical Analysis 63
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Sleep: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0259 |
| 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: 0.23 |
|
| Estimation Comments | ||
Statistical Analysis 64
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Sleep: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5243 |
| 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 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.23 |
|
| Estimation Comments | ||
Statistical Analysis 65
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Sleep: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8488 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.23 |
|
| Estimation Comments | ||
Statistical Analysis 66
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | Enjoyment of life: Placebo vs Pregabalin 150 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2746 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.22 |
|
| Estimation Comments | ||
Statistical Analysis 67
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg QD |
|---|---|---|
| Comments | Enjoyment of life: Placebo vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9349 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.22 |
|
| Estimation Comments | ||
Statistical Analysis 68
| Statistical Analysis Overview | Comparison Group Selection | Placebo, DS-5565 15 mg BID |
|---|---|---|
| Comments | Enjoyment of life: Placebo vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5164 |
| 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 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.22 |
|
| Estimation Comments | ||
Statistical Analysis 69
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg QD |
|---|---|---|
| Comments | Enjoyment of life: Pregabalin 150 mg BID vs DS-5565 15 mg QD | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2382 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.22 |
|
| Estimation Comments | ||
Statistical Analysis 70
| Statistical Analysis Overview | Comparison Group Selection | Pregabalin 150 mg BID, DS-5565 15 mg BID |
|---|---|---|
| Comments | Enjoyment of life: Pregabalin 150 mg BID vs DS-5565 15 mg BID | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0807 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.0 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.22 |
|
| 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 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 | 318 | 317 | 319 | 319 |
| Mean (Standard Deviation) [proportion of days] |
0.23
(0.32)
|
0.18
(0.30)
|
0.22
(0.31)
|
0.19
(0.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Pregabalin 150 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0601 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.045 | |
| Confidence Interval |
(2-Sided) 95% -0.091 to 0.002 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0237 |
|
| Estimation Comments | ||
Statistical Analysis 2
| 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 | 0.8299 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.005 | |
| Confidence Interval |
(2-Sided) 95% -0.052 to 0.041 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0237 |
|
| Estimation Comments | ||
Statistical Analysis 3
| 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 | 0.0347 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.050 | |
| Confidence Interval |
(2-Sided) 95% -0.096 to 0.004 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0237 |
|
| 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 | 0.0951 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | 0.040 | |
| Confidence Interval |
(2-Sided) 95% -0.007 to 0.086 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0237 |
|
| 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 | 0.8199 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares means |
| Estimated Value | -0.005 | |
| Confidence Interval |
(2-Sided) 95% -0.052 to 0.041 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0237 |
|
| 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 1 year 9 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 | DS-5565 QD | DS-5565 BID | ||||
| Arm/Group Description | Placebo for oral administration matching capsule for DS-5565 and matching tablet for pregabalin | Participants take one pregabalin capsule and one placebo tablet BID | Participants take one each of placebo tablet and capsule in the morning and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening | Participants take one DS-5565 tablet and one placebo capsule BID | ||||
All Cause Mortality |
||||||||
| Placebo | Pregabalin | DS-5565 QD | DS-5565 BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/318 (0%) | 0/318 (0%) | 0/320 (0%) | 0/320 (0%) | ||||
Serious Adverse Events |
||||||||
| Placebo | Pregabalin | DS-5565 QD | DS-5565 BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/318 (3.5%) | 2/318 (0.6%) | 5/320 (1.6%) | 8/320 (2.5%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Colitis | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 1/320 (0.3%) | 1 | 0/320 (0%) | 0 |
| Salivary gland calculus | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| General disorders | ||||||||
| Non-cardiac chest pain | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 2/320 (0.6%) | 2 |
| Catheter site haemorrhage | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 1/320 (0.3%) | 1 | 0/320 (0%) | 0 |
| Pyrexia | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Infections and infestations | ||||||||
| Appendicitis | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 1/320 (0.3%) | 1 |
| Bronchitis | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 1/320 (0.3%) | 1 | 0/320 (0%) | 0 |
| Infectious colitis | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 1/320 (0.3%) | 1 |
| Staphylococcal infection | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 1/320 (0.3%) | 1 | 0/320 (0%) | 0 |
| Cellulitis | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Gastroenteritis | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Sepsis | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Investigations | ||||||||
| Transaminases increased | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back disorder | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 1/320 (0.3%) | 1 |
| Back pain | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 1/320 (0.3%) | 1 |
| Spinal osteoarthritis | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| B-cell lymphoma | 0/318 (0%) | 0 | 1/318 (0.3%) | 1 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Suicide attempt | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 1/320 (0.3%) | 1 |
| Withdrawal syndrome | 0/318 (0%) | 0 | 1/318 (0.3%) | 1 | 0/320 (0%) | 0 | 1/320 (0.3%) | 1 |
| Suicidal ideation | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Calculus ureteric | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Postmenopausal haemorrhage | 0/318 (0%) | 0 | 1/318 (0.3%) | 1 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 1/320 (0.3%) | 1 | 0/320 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/318 (0%) | 0 | 0/318 (0%) | 0 | 1/320 (0.3%) | 1 | 0/320 (0%) | 0 |
| Bronchospasm | 1/318 (0.3%) | 1 | 0/318 (0%) | 0 | 0/320 (0%) | 0 | 0/320 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | Pregabalin | DS-5565 QD | DS-5565 BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 145/318 (45.6%) | 247/318 (77.7%) | 229/320 (71.6%) | 251/320 (78.4%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 19/318 (6%) | 19 | 27/318 (8.5%) | 27 | 27/320 (8.4%) | 27 | 36/320 (11.3%) | 36 |
| Dry mouth | 5/318 (1.6%) | 5 | 21/318 (6.6%) | 21 | 15/320 (4.7%) | 15 | 18/320 (5.6%) | 18 |
| Diarrhoea | 14/318 (4.4%) | 14 | 10/318 (3.1%) | 10 | 10/320 (3.1%) | 10 | 16/320 (5%) | 16 |
| General disorders | ||||||||
| Fatigue | 10/318 (3.1%) | 10 | 23/318 (7.2%) | 23 | 23/320 (7.2%) | 23 | 36/320 (11.3%) | 36 |
| Oedema peripheral | 11/318 (3.5%) | 11 | 19/318 (6%) | 19 | 14/320 (4.4%) | 14 | 11/320 (3.4%) | 11 |
| Infections and infestations | ||||||||
| Nasopharyngitis | 24/318 (7.5%) | 24 | 21/318 (6.6%) | 21 | 22/320 (6.9%) | 22 | 21/320 (6.6%) | 21 |
| Investigations | ||||||||
| Weight increased | 16/318 (5%) | 16 | 36/318 (11.3%) | 36 | 21/320 (6.6%) | 21 | 36/320 (11.3%) | 36 |
| Nervous system disorders | ||||||||
| Dizziness | 20/318 (6.3%) | 20 | 65/318 (20.4%) | 65 | 53/320 (16.6%) | 53 | 71/320 (22.2%) | 71 |
| Headache | 36/318 (11.3%) | 36 | 48/318 (15.1%) | 48 | 45/320 (14.1%) | 45 | 55/320 (17.2%) | 55 |
| Somnolence | 7/318 (2.2%) | 7 | 37/318 (11.6%) | 37 | 25/320 (7.8%) | 25 | 39/320 (12.2%) | 39 |
| Psychiatric disorders | ||||||||
| Insomnia | 7/318 (2.2%) | 7 | 13/318 (4.1%) | 13 | 16/320 (5%) | 16 | 22/320 (6.9%) | 22 |
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:
NCT02146430
Other Study ID Numbers:
- DS5565-A-E309
- 2013-005161-40
First Posted:
May 23, 2014
Last Update Posted:
Nov 9, 2020
Last Verified:
Nov 1, 2020