Trial Outcomes & Findings for Treatment of Pain Associated With Fibromyalgia (NCT NCT02146430)

Last Updated: 2020-11-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1293 participants

Primary outcome timeframe

Baseline up to Week 13 postdose

Results posted on

2020-11-09

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 QD Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 BID Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Overall Study STARTED	323	323	324	323
Overall Study Safety Analysis Set	318	318	320	320
Overall Study Modified Intent to Treat Set (mITT)	318	317	319	319
Overall Study COMPLETED	256	236	242	224
Overall Study NOT COMPLETED	67	87	82	99

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 QD Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 BID Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Overall Study Protocol Violation	5	4	8	6
Overall Study Lack of Efficacy	13	11	8	5
Overall Study Adverse Event	20	40	32	49
Overall Study Reason missing or not reported	2	3	4	5
Overall Study Withdrawal by Subject	27	29	30	34

Baseline Characteristics

Treatment of Pain Associated With Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=323 Participants Placebo for oral administration matching capsule for DS-5565 and matching tablet for pregabalin	Pregabalin n=323 Participants Participants take one pregabalin capsule and one placebo tablet BID	DS-5565 QD n=324 Participants 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	DS-5565 BID n=323 Participants Participants take one DS-5565 tablet and one placebo capsule BID	Total n=1293 Participants Total of all reporting groups
Age, Continuous	48.6 years STANDARD_DEVIATION 11.76 • n=5 Participants	49.5 years STANDARD_DEVIATION 11.53 • n=7 Participants	50.3 years STANDARD_DEVIATION 10.88 • n=5 Participants	49.5 years STANDARD_DEVIATION 11.77 • n=4 Participants	49.5 years STANDARD_DEVIATION 11.49 • n=21 Participants
Age, Customized Age Categorical · 18-64 Years	298 Participants n=5 Participants	298 Participants n=7 Participants	300 Participants n=5 Participants	287 Participants n=4 Participants	1183 Participants n=21 Participants
Age, Customized Age Categorical · 65-84 Years	25 Participants n=5 Participants	24 Participants n=7 Participants	24 Participants n=5 Participants	36 Participants n=4 Participants	109 Participants n=21 Participants
Age, Customized Age Categorical · 85 Years and over	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Sex: Female, Male Female	299 Participants n=5 Participants	292 Participants n=7 Participants	286 Participants n=5 Participants	291 Participants n=4 Participants	1168 Participants n=21 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	31 Participants n=7 Participants	38 Participants n=5 Participants	32 Participants n=4 Participants	125 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change From Baseline in Weekly Average Daily Pain Score (ADPS) at Week 13 in Participants Receiving DS-5565, Pregabalin, Placebo	-1.66 units on a scale Standard Error 0.132	-1.90 units on a scale Standard Error 0.134	-1.97 units on a scale Standard Error 0.134	-1.93 units on a scale Standard Error 0.136

SECONDARY outcome

Timeframe: Baseline up Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
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	83 Participants	105 Participants	104 Participants	82 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change in Fibromyalgia Index Questionnaire (FIQ) Total Score From Baseline to Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo	-13.20 units on a scale Standard Deviation 1.173	-16.60 units on a scale Standard Deviation 1.166	-14.48 units on a scale Standard Deviation 1.191	-13.13 units on a scale Standard Deviation 1.199

SECONDARY outcome

Timeframe: Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

The number of participants with at least a 30% or 50% reduction in average daily pain score (ADPS) at Week 13 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo 30% responders	101 Participants	118 Participants	106 Participants	100 Participants
Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo 50% responders	57 Participants	71 Participants	71 Participants	57 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 13 postdose

Population: This outcome was assessed in the modified intent-to-treat analysis set.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo	-1.9 units on a scale Standard Deviation 3.4	-2.0 units on a scale Standard Deviation 3.82	-2.0 units on a scale Standard Deviation 3.51	-1.6 units on a scale Standard Deviation 3.38

SECONDARY outcome

Timeframe: Baseline up to Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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).

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo Change from baseline to Week 13: Anxiety	-1.0 units on a scale Standard Deviation 3.17	-0.8 units on a scale Standard Deviation 3.04	-1.0 units on a scale Standard Deviation 3.25	-1.1 units on a scale Standard Deviation 3.34
Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo Change from baseline to Week 13: Depression	-0.8 units on a scale Standard Deviation 3.54	-1.1 units on a scale Standard Deviation 3.23	-0.8 units on a scale Standard Deviation 3.52	-0.6 units on a scale Standard Deviation 3.30

SECONDARY outcome

Timeframe: Baseline up to Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo Change from baseline to Week 13: Mental Component	1.506 units on a scale Standard Deviation 9.25	1.995 units on a scale Standard Deviation 8.59	1.163 units on a scale Standard Deviation 9.32	1.286 units on a scale Standard Deviation 8.85
Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo Change from baseline to Week 13:Physical Component	8.052 units on a scale Standard Deviation 19.91	9.898 units on a scale Standard Deviation 16.73	8.598 units on a scale Standard Deviation 18.62	7.099 units on a scale Standard Deviation 19.52

SECONDARY outcome

Timeframe: Baseline up to Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo	0.0779 units on a scale Standard Deviation 0.190	0.0712 units on a scale Standard Deviation 0.182	0.0740 units on a scale Standard Deviation 0.173	0.0696 units on a scale Standard Deviation 0.185

SECONDARY outcome

Timeframe: Baseline up Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change From Baseline to Week 13 in Average Daily Sleep Interference in Participants Receiving DS-5565, Pregabalin, or Placebo	-1.67 units on a scale Standard Error 0.120	-2.22 units on a scale Standard Error 0.120	-2.30 units on a scale Standard Error 0.121	-2.52 units on a scale Standard Error 0.121

SECONDARY outcome

Timeframe: Week 13 postdose

Population: This outcome was assessed in the modified intent-to-treat analysis set.

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).

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
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	87 Participants	117 Participants	93 Participants	109 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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.

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Worst pain	6.6 units on a scale Standard Error 1.41	6.3 units on a scale Standard Error 1.50	6.5 units on a scale Standard Error 1.48	6.6 units on a scale Standard Error 1.47
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Least pain	-1.2 units on a scale Standard Error 0.13	-1.5 units on a scale Standard Error 0.13	-1.3 units on a scale Standard Error 0.13	-1.3 units on a scale Standard Error 0.13
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Average pain	-1.2 units on a scale Standard Error 0.12	-1.5 units on a scale Standard Error 0.12	-1.4 units on a scale Standard Error 0.12	-1.4 units on a scale Standard Error 0.12
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Pain right now	-1.7 units on a scale Standard Error 0.14	-1.9 units on a scale Standard Error 0.14	-1.7 units on a scale Standard Error 0.14	-1.7 units on a scale Standard Error 0.14
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Severity score	-1.4 units on a scale Standard Error 0.12	-1.7 units on a scale Standard Error 0.12	-1.5 units on a scale Standard Error 0.12	-1.5 units on a scale Standard Error 0.12
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Relief (%) by treatment pain	15.9 units on a scale Standard Error 1.78	18.5 units on a scale Standard Error 1.74	17.1 units on a scale Standard Error 1.77	15.6 units on a scale Standard Error 1.76
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Interference (%)	-14.04 units on a scale Standard Error 1.30	-17.91 units on a scale Standard Error 1.28	-15.46 units on a scale Standard Error 1.30	-15.65 units on a scale Standard Error 1.29
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo General activity	-1.5 units on a scale Standard Error 0.15	-1.9 units on a scale Standard Error 0.15	-1.6 units on a scale Standard Error 0.15	-1.6 units on a scale Standard Error 0.15
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Mood	-1.1 units on a scale Standard Error 0.16	-1.6 units on a scale Standard Error 0.15	-1.3 units on a scale Standard Error 0.15	-1.3 units on a scale Standard Error 0.15
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Walking ability	-1.1 units on a scale Standard Error 0.16	-1.5 units on a scale Standard Error 0.15	-1.1 units on a scale Standard Error 0.15	-1.1 units on a scale Standard Error 0.15
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Normal work	-1.5 units on a scale Standard Error 0.15	-1.8 units on a scale Standard Error 0.15	-1.5 units on a scale Standard Error 0.15	-1.5 units on a scale Standard Error 0.15
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Relations with other people	-0.9 units on a scale Standard Error 0.15	-1.3 units on a scale Standard Error 0.15	-1.3 units on a scale Standard Error 0.15	-1.3 units on a scale Standard Error 0.15
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Sleep	-2.1 units on a scale Standard Error 0.17	-2.7 units on a scale Standard Error 0.17	-2.5 units on a scale Standard Error 0.17	-2.6 units on a scale Standard Error 0.17
Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo Enjoyment of life	-1.6 units on a scale Standard Error 0.16	-1.9 units on a scale Standard Error 0.16	-1.6 units on a scale Standard Error 0.16	-1.5 units on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: Week 1 to Week 13 postdose

Population: This outcome was assessed using the modified intent-to-treat analysis set.

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).

Outcome measures

Outcome measures
Measure	Placebo n=318 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.	Pregabalin 150 mg BID n=317 Participants Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.	DS-5565 15 mg QD n=319 Participants Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.	DS-5565 15 mg BID n=319 Participants Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.
Proportion of Days a Rescue Medication Was Used Among Participants Receiving DS-5565, Pregabalin, or Placebo	0.23 proportion of days Standard Deviation 0.32	0.18 proportion of days Standard Deviation 0.30	0.22 proportion of days Standard Deviation 0.31	0.19 proportion of days Standard Deviation 0.28

Adverse Events

Placebo

Serious events: 11 serious events

Other events: 145 other events

Deaths: 0 deaths

Pregabalin

Serious events: 2 serious events

Other events: 247 other events

Deaths: 0 deaths

DS-5565 QD

Serious events: 5 serious events

Other events: 229 other events

Deaths: 0 deaths

DS-5565 BID

Serious events: 8 serious events

Other events: 251 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=318 participants at risk Placebo for oral administration matching capsule for DS-5565 and matching tablet for pregabalin	Pregabalin n=318 participants at risk Participants take one pregabalin capsule and one placebo tablet BID	DS-5565 QD n=320 participants at risk 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	DS-5565 BID n=320 participants at risk Participants take one DS-5565 tablet and one placebo capsule BID
General disorders Oedema peripheral	3.5% 11/318 • Number of events 11 • 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. 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.	6.0% 19/318 • Number of events 19 • 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. 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.	4.4% 14/320 • Number of events 14 • 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. 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.	3.4% 11/320 • Number of events 11 • 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. 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.
Investigations Weight increased	5.0% 16/318 • Number of events 16 • 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. 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.	11.3% 36/318 • Number of events 36 • 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. 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.	6.6% 21/320 • Number of events 21 • 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. 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.	11.2% 36/320 • Number of events 36 • 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. 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.
Nervous system disorders Dizziness	6.3% 20/318 • Number of events 20 • 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. 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.	20.4% 65/318 • Number of events 65 • 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. 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.	16.6% 53/320 • Number of events 53 • 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. 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.	22.2% 71/320 • Number of events 71 • 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. 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.
Nervous system disorders Headache	11.3% 36/318 • Number of events 36 • 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. 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.	15.1% 48/318 • Number of events 48 • 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. 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.	14.1% 45/320 • Number of events 45 • 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. 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.	17.2% 55/320 • Number of events 55 • 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. 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.
Nervous system disorders Somnolence	2.2% 7/318 • Number of events 7 • 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. 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.	11.6% 37/318 • Number of events 37 • 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. 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.	7.8% 25/320 • Number of events 25 • 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. 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.	12.2% 39/320 • Number of events 39 • 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. 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.
General disorders Fatigue	3.1% 10/318 • Number of events 10 • 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. 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.	7.2% 23/318 • Number of events 23 • 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. 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.	7.2% 23/320 • Number of events 23 • 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. 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.	11.2% 36/320 • Number of events 36 • 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. 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.
Psychiatric disorders Insomnia	2.2% 7/318 • Number of events 7 • 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. 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.	4.1% 13/318 • Number of events 13 • 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. 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.	5.0% 16/320 • Number of events 16 • 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. 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.	6.9% 22/320 • Number of events 22 • 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. 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.
Gastrointestinal disorders Nausea	6.0% 19/318 • Number of events 19 • 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. 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.	8.5% 27/318 • Number of events 27 • 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. 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.	8.4% 27/320 • Number of events 27 • 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. 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.	11.2% 36/320 • Number of events 36 • 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. 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.
Gastrointestinal disorders Dry mouth	1.6% 5/318 • Number of events 5 • 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. 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.	6.6% 21/318 • Number of events 21 • 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. 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.	4.7% 15/320 • Number of events 15 • 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. 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.	5.6% 18/320 • Number of events 18 • 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. 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.
Gastrointestinal disorders Diarrhoea	4.4% 14/318 • Number of events 14 • 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. 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.	3.1% 10/318 • Number of events 10 • 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. 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.	3.1% 10/320 • Number of events 10 • 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. 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.	5.0% 16/320 • Number of events 16 • 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. 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.
Infections and infestations Nasopharyngitis	7.5% 24/318 • Number of events 24 • 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. 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.	6.6% 21/318 • Number of events 21 • 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. 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.	6.9% 22/320 • Number of events 22 • 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. 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.	6.6% 21/320 • Number of events 21 • 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. 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.

Additional Information

Daiichi Sankyo US Contact for Clinical Trial Results

Daiichi Sankyo, Inc.

Phone: +1 (908) 992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place