Trial Outcomes & Findings for An Open-Label Extension Study of DS-5565 for 52 Weeks in Pain Associated With Fibromyalgia (NCT NCT02234583)

Last Updated: 2020-07-23

Results Overview

Average of daily pain scores are reported by the participant and best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale of 0 = no pain to 10 = worst possible pain.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2485 participants

Primary outcome timeframe

Day 0 (baseline) up to to Week 52 postdose

Results posted on

2020-07-23

Participant Flow

A total of 2485 participants who met all inclusion and no exclusion criteria enrolled from 04 Feb 2015 to 19 Apr 2017 at 406 clinic sites. Of the 2485 enrolled, 397 discontinued prior to randomization. A total of 2088 participants received study treatment.

Participants who completed the double-blind studies of DS-5565 in fibromyalgia were eligible to Rollover to this open-label extension study (referred to as Rollover participants). Participants who did not participate in a preceding double-blind study (referred to as De Novo participants) could be enrolled at the discretion of the Sponsor.

Participant milestones

Participant milestones
Measure	DS-5565 15 mg QD Modal Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo QD modal.	DS-5565 15 mg BID Modal Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo twice daily (BID) modal.
Overall Study STARTED	847	1241
Overall Study COMPLETED	434	685
Overall Study NOT COMPLETED	413	556

Reasons for withdrawal

Reasons for withdrawal
Measure	DS-5565 15 mg QD Modal Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo QD modal.	DS-5565 15 mg BID Modal Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo twice daily (BID) modal.
Overall Study Adverse Event	172	156
Overall Study Withdrawal by Subject	109	157
Overall Study Lost to Follow-up	0	1
Overall Study Lack of Efficacy	58	103
Overall Study Protocol Violation	35	42
Overall Study Other	39	97

Baseline Characteristics

An Open-Label Extension Study of DS-5565 for 52 Weeks in Pain Associated With Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DS-5565 15 mg QD Modal n=847 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo QD modal.	DS-5565 15 mg BID Modal n=1241 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). This group includes both rollover and De Novo BID modal.	Total n=2088 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Age, Categorical Between 18 and 65 years	750 Participants n=113 Participants	1128 Participants n=163 Participants	1878 Participants n=160 Participants
Age, Categorical >=65 years	97 Participants n=113 Participants	113 Participants n=163 Participants	210 Participants n=160 Participants
Age, Continuous	51.4 years STANDARD_DEVIATION 11.18 • n=113 Participants	49.3 years STANDARD_DEVIATION 11.94 • n=163 Participants	50.2 years STANDARD_DEVIATION 11.68 • n=160 Participants
Sex: Female, Male Female	770 Participants n=113 Participants	1130 Participants n=163 Participants	1900 Participants n=160 Participants
Sex: Female, Male Male	77 Participants n=113 Participants	111 Participants n=163 Participants	188 Participants n=160 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=113 Participants	4 Participants n=163 Participants	8 Participants n=160 Participants
Race (NIH/OMB) Asian	2 Participants n=113 Participants	5 Participants n=163 Participants	7 Participants n=160 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Black or African American	82 Participants n=113 Participants	113 Participants n=163 Participants	195 Participants n=160 Participants
Race (NIH/OMB) White	740 Participants n=113 Participants	1101 Participants n=163 Participants	1841 Participants n=160 Participants
Race (NIH/OMB) More than one race	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants
Race (NIH/OMB) Unknown or Not Reported	19 Participants n=113 Participants	18 Participants n=163 Participants	37 Participants n=160 Participants
Region of Enrollment United States	569 participants n=113 Participants	913 participants n=163 Participants	1879 participants n=160 Participants
Region of Enrollment Czechia	11 participants n=113 Participants	27 participants n=163 Participants	38 participants n=160 Participants
Region of Enrollment Portugal	0 participants n=113 Participants	4 participants n=163 Participants	4 participants n=160 Participants
Region of Enrollment Russia	10 participants n=113 Participants	1 participants n=163 Participants	11 participants n=160 Participants
Region of Enrollment Austria	5 participants n=113 Participants	10 participants n=163 Participants	15 participants n=160 Participants
Region of Enrollment Latvia	11 participants n=113 Participants	8 participants n=163 Participants	19 participants n=160 Participants
Region of Enrollment Poland	16 participants n=113 Participants	24 participants n=163 Participants	40 participants n=160 Participants
Region of Enrollment Slovakia	14 participants n=113 Participants	4 participants n=163 Participants	18 participants n=160 Participants
Region of Enrollment Slovenia	4 participants n=113 Participants	3 participants n=163 Participants	7 participants n=160 Participants
Region of Enrollment Bulgaria	14 participants n=113 Participants	6 participants n=163 Participants	20 participants n=160 Participants
Region of Enrollment Chile	1 participants n=113 Participants	4 participants n=163 Participants	5 participants n=160 Participants
Region of Enrollment France	4 participants n=113 Participants	2 participants n=163 Participants	6 participants n=160 Participants
Region of Enrollment Lithuania	3 participants n=113 Participants	1 participants n=163 Participants	4 participants n=160 Participants
Region of Enrollment Serbia	0 participants n=113 Participants	3 participants n=163 Participants	3 participants n=160 Participants
Region of Enrollment Romania	3 participants n=113 Participants	1 participants n=163 Participants	4 participants n=160 Participants
Region of Enrollment Hungary	6 participants n=113 Participants	1 participants n=163 Participants	7 participants n=160 Participants
Region of Enrollment Ukraine	73 participants n=113 Participants	59 participants n=163 Participants	264 participants n=160 Participants
Region of Enrollment United Kingdom	14 participants n=113 Participants	27 participants n=163 Participants	41 participants n=160 Participants
Region of Enrollment Spain	8 participants n=113 Participants	19 participants n=163 Participants	27 participants n=160 Participants
Region of Enrollment New Zealand	7 participants n=113 Participants	11 participants n=163 Participants	18 participants n=160 Participants
Region of Enrollment Canada	17 participants n=113 Participants	35 participants n=163 Participants	52 participants n=160 Participants
Region of Enrollment Norway	12 participants n=113 Participants	30 participants n=163 Participants	42 participants n=160 Participants
Region of Enrollment Finland	0 participants n=113 Participants	1 participants n=163 Participants	1 participants n=160 Participants
Region of Enrollment Denmark	7 participants n=113 Participants	5 participants n=163 Participants	12 participants n=160 Participants
Region of Enrollment South Africa	9 participants n=113 Participants	10 participants n=163 Participants	38 participants n=160 Participants
Region of Enrollment Australia	5 participants n=113 Participants	8 participants n=163 Participants	13 participants n=160 Participants
Region of Enrollment Germany	22 participants n=113 Participants	16 participants n=163 Participants	38 participants n=160 Participants
Region of Enrollment Estonia	2 participants n=113 Participants	8 participants n=163 Participants	10 participants n=160 Participants

PRIMARY outcome

Timeframe: Day 0 (baseline) up to to Week 52 postdose

Population: Average daily pain score was assessed in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Rollover DS-5565 15 mg QD Modal n=578 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	Rollover DS-5565 15 mg BID Modal n=962 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg QD Modal n=269 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg BID Modal n=279 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.
Average Daily Pain Score (ADPS) for DS-5565 Baseline	4.77 score on a scale Standard Deviation 2.23	5.58 score on a scale Standard Deviation 2.22	7.08 score on a scale Standard Deviation 1.40	7.38 score on a scale Standard Deviation 1.37
Average Daily Pain Score (ADPS) for DS-5565 Week 13	3.47 score on a scale Standard Deviation 2.11	4.36 score on a scale Standard Deviation 2.32	3.21 score on a scale Standard Deviation 2.20	4.06 score on a scale Standard Deviation 2.37
Average Daily Pain Score (ADPS) for DS-5565 Week 24	3.28 score on a scale Standard Deviation 2.08	4.24 score on a scale Standard Deviation 2.35	3.0 score on a scale Standard Deviation 2.14	4.0 score on a scale Standard Deviation 2.38
Average Daily Pain Score (ADPS) for DS-5565 Week 36	3.20 score on a scale Standard Deviation 2.06	4.25 score on a scale Standard Deviation 2.34	2.74 score on a scale Standard Deviation 2.23	3.95 score on a scale Standard Deviation 2.59
Average Daily Pain Score (ADPS) for DS-5565 Week 48	3.22 score on a scale Standard Deviation 2.16	4.25 score on a scale Standard Deviation 2.37	2.46 score on a scale Standard Deviation 2.15	3.80 score on a scale Standard Deviation 2.61
Average Daily Pain Score (ADPS) for DS-5565 Week 52	3.20 score on a scale Standard Deviation 2.18	4.26 score on a scale Standard Deviation 2.42	2.31 score on a scale Standard Deviation 1.94	3.80 score on a scale Standard Deviation 2.70

SECONDARY outcome

Timeframe: Week 52 postdose

Population: Patient Global Impression of Change was assessed in the Safety Analysis Set.

Patient-rated global impression of change (PGIC) on a categorical scale from 1 = very much improved to 7 = very much worse. The number of participants with "much improved or better" status are reported.

Outcome measures

Outcome measures
Measure	Rollover DS-5565 15 mg QD Modal n=578 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	Rollover DS-5565 15 mg BID Modal n=962 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg QD Modal n=269 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg BID Modal n=279 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.
Number of Participants With Much Improved or Better (≤2) Status in Status at Week 52 As Assessed by the Patient-Rated Global Impression of Change	208 Participants	333 Participants	96 Participants	92 Participants

SECONDARY outcome

Timeframe: Day 0 (baseline) up to Week 52 postdose

Population: HADS-Depression and Anxiety was assessed in the Safety Analysis Set.

The HADS questionnaire is a 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 from 0 to 3, where higher scores indicate greater anxiety or depression. Scores for anxiety and depression are independently summed to compute HADS-Anxiety and HADS-Depression subscale scores, with ranges from 0 to 21, where higher scores indicate greater severity.

Outcome measures

Outcome measures
Measure	Rollover DS-5565 15 mg QD Modal n=578 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	Rollover DS-5565 15 mg BID Modal n=962 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg QD Modal n=269 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg BID Modal n=279 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.
Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 Anxiety Subscale Baseline	5.7 score on a scale Standard Deviation 3.86	7.2 score on a scale Standard Deviation 4.05	6.9 score on a scale Standard Deviation 3.97	7.4 score on a scale Standard Deviation 4.21
Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 Anxiety Subscale Week 52	4.8 score on a scale Standard Deviation 3.71	7.0 score on a scale Standard Deviation 4.03	4.4 score on a scale Standard Deviation 3.29	5.7 score on a scale Standard Deviation 3.88
Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 Depression Subscale Baseline	5.1 score on a scale Standard Deviation 4.18	6.3 score on a scale Standard Deviation 4.34	5.6 score on a scale Standard Deviation 4.06	5.7 score on a scale Standard Deviation 4.10
Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 Depression Subscale Week 52	3.5 score on a scale Standard Deviation 3.47	4.8 score on a scale Standard Deviation 4.01	2.8 score on a scale Standard Deviation 3.11	3.9 score on a scale Standard Deviation 4.00

SECONDARY outcome

Timeframe: Day 0 (baseline) up to Week 52 postdose

Population: EQ-5D was assessed in the Safety 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) that are combined into an overall health utilities index, and an NRS (100 mm VAS) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health.

Outcome measures

Outcome measures
Measure	Rollover DS-5565 15 mg QD Modal n=578 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	Rollover DS-5565 15 mg BID Modal n=962 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg QD Modal n=269 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg BID Modal n=279 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.
EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 Total Score Baseline	0.70 units on a scale Standard Deviation 0.17	0.64 units on a scale Standard Deviation 0.19	0.62 units on a scale Standard Deviation 0.16	0.61 units on a scale Standard Deviation 0.18
EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 Total Score Week 52	0.76 units on a scale Standard Deviation 0.16	0.70 units on a scale Standard Deviation 0.20	0.81 units on a scale Standard Deviation 0.15	0.77 units on a scale Standard Deviation 0.17

SECONDARY outcome

Timeframe: Day 0 (baseline) to Week 52 postdose

Population: SF-36 was assessed in the Safety 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 physical component summary and mental component summary scales range 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) total scores at baseline and Week 52 are reported.

Outcome measures

Outcome measures
Measure	Rollover DS-5565 15 mg QD Modal n=578 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	Rollover DS-5565 15 mg BID Modal n=962 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg QD Modal n=269 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg BID Modal n=279 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.
Short Form-36 (SF-36) Measure for DS-5565 Physical Component Summary Baseline	37.91 score on a scale Standard Deviation 8.86	35.13 score on a scale Standard Deviation 8.55	34.41 score on a scale Standard Deviation 8.58	32.12 score on a scale Standard Deviation 7.85
Short Form-36 (SF-36) Measure for DS-5565 Physical Component Summary Week 52	42.96 score on a scale Standard Deviation 8.52	39.09 score on a scale Standard Deviation 9.38	45.61 score on a scale Standard Deviation 9.63	42.31 score on a scale Standard Deviation 10.47
Short Form-36 (SF-36) Measure for DS-5565 Mental Component Summary Baseline	50.12 score on a scale Standard Deviation 10.19	47.76 score on a scale Standard Deviation 11.15	47.54 score on a scale Standard Deviation 10.98	47.92 score on a scale Standard Deviation 11.46
Short Form-36 (SF-36) Measure for DS-5565 Mental Component Summary Week 52	52.63 score on a scale Standard Deviation 9.61	49.15 score on a scale Standard Deviation 11.24	52.75 score on a scale Standard Deviation 8.02	50.49 score on a scale Standard Deviation 10.54

SECONDARY outcome

Timeframe: Day 0 (baseline) up to Week 52 postdose

Population: Average Daily Sleep Interference Score was assessed in the Safety 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. For rollover participants, the baseline scores from the End-of-Tapering period in the preceding study are reported. For de novo participants, the baseline scores are derived from the 7 days prior to the start of treatment.

Outcome measures

Outcome measures
Measure	Rollover DS-5565 15 mg QD Modal n=578 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	Rollover DS-5565 15 mg BID Modal n=962 Participants Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309 \[NCT02146430\], DS5565-A-E310 \[NCT02187471\], or DS5565-A-E311 \[NCT02187159\]) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg QD Modal n=269 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.	De Novo DS-5565 15 mg BID Modal n=279 Participants Participants with no prior exposure to DS-5565 and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to twice daily (BID). Participants were reported by their modal dose or dose received most frequently.
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 Baseline	3.84 score on a scale Standard Deviation 2.41	4.74 score on a scale Standard Deviation 2.52	6.71 score on a scale Standard Deviation 1.70	6.82 score on a scale Standard Deviation 1.82
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 Week 13	2.56 score on a scale Standard Deviation 2.16	3.18 score on a scale Standard Deviation 2.50	2.50 score on a scale Standard Deviation 2.15	3.13 score on a scale Standard Deviation 2.51
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 Week 24	2.34 score on a scale Standard Deviation 1.96	3.09 score on a scale Standard Deviation 2.50	2.36 score on a scale Standard Deviation 2.18	3.19 score on a scale Standard Deviation 2.48
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 Week 36	2.25 score on a scale Standard Deviation 1.98	3.09 score on a scale Standard Deviation 2.50	2.19 score on a scale Standard Deviation 2.20	3.11 score on a scale Standard Deviation 2.63
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 Week 48	2.32 score on a scale Standard Deviation 2.07	3.22 score on a scale Standard Deviation 2.56	1.87 score on a scale Standard Deviation 2.05	3.02 score on a scale Standard Deviation 2.64
Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 Week 52	2.22 score on a scale Standard Deviation 2.06	3.19 score on a scale Standard Deviation 2.63	1.79 score on a scale Standard Deviation 1.86	3.09 score on a scale Standard Deviation 2.71

Adverse Events

DS-5565 15 mg QD Modal

Serious events: 41 serious events

Other events: 669 other events

Deaths: 3 deaths

DS-5565 15 mg BID Modal

Serious events: 94 serious events

Other events: 1056 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

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
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Measure	DS-5565 15 mg QD Modal n=847 participants at risk Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309, DS5565-A-E310, or DS5565-A-E311) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo QD modal.	DS-5565 15 mg BID Modal n=1241 participants at risk Participants received DS-5565 in a preceding Phase 3 study of DS-5565 in fibromyalgia (DS5565-A-E309, DS5565-A-E310, or DS5565-A-E311) and received 15 mg DS-5565 administered once daily (QD) for the first 3 weeks. After 3 weeks, participants could be titrated to BID. This group includes both rollover and De Novo twice daily (BID) modal.
Infections and infestations Upper respiratory tract infection	5.1% 43/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	10.8% 134/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Infections and infestations Urinary tract infection	6.0% 51/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	8.6% 107/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Infections and infestations Nasopharyngitis	5.5% 47/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	8.9% 110/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Infections and infestations Sinusitis	4.3% 36/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	7.2% 89/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Nervous system disorders Dizziness	15.8% 134/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	11.9% 148/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Nervous system disorders Headache	14.5% 123/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	12.7% 158/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Nervous system disorders Somnolence	15.3% 130/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	8.2% 102/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
General disorders Drug withdrawal syndrome	7.2% 61/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	10.9% 135/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
General disorders Fatigue	9.0% 76/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	6.7% 83/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
General disorders Oedema peripheral	6.1% 52/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	6.6% 82/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Musculoskeletal and connective tissue disorders Back pain	4.1% 35/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	7.2% 89/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 32/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	7.1% 88/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Musculoskeletal and connective tissue disorders Pain in extremity	3.2% 27/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	5.2% 64/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Musculoskeletal and connective tissue disorders Fibromyalgia	3.1% 26/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	5.0% 62/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Gastrointestinal disorders Nausea	7.2% 61/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	9.1% 113/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Gastrointestinal disorders Diarrhoea	4.7% 40/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	7.8% 97/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Investigations Weight increased	9.8% 83/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	16.7% 207/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Psychiatric disorders Insomnia	4.0% 34/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	5.1% 63/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.
Eye disorders Vision blurred	3.1% 26/847 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.	4.5% 56/1241 • Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months. A TEAE was any adverse event that emerged on or after the first dosing of open-label extension (OLE) medication and during study treatment up to 4 weeks after the last dose of OLE medication (having been absent prior to treatment) or worsened relative to the pre-OLE treatment state.