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

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02234583
• Collaborator: (none)
• Enrollment: 2,485
• Locations: 276
• Arm: 1
• Actual Duration (Months): 26.4
• Patients Per Site: 9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is an open-label study of DS-5565 in subjects who either completed participation in a preceding Phase 3 study of DS-5565 in fibromyalgia (FM); i.e. DS5565-A-E309 (NCT02146430), DS5565-A-E310 (NCT02187471), or DS5565-A-E311 (NCT02187159) or are de novo subjects. Eligible subjects will be assigned to receive open-label DS-5565 for 52 weeks. All subjects will receive DS-5565 15 mg once daily (QD) for the first three weeks of the treatment period. After three weeks, subjects may be titrated to 15 mg twice daily (BID) based on protocol-specified criteria.

Condition or Disease	Intervention/Treatment	Phase
Pain Associated With Fibromyalgia	Drug: DS-5565	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2485 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Extension Study of DS-5565 for 52 Weeks in Pain Associated With Fibromyalgia
• Actual Study Start Date: Feb 4, 2015
• Actual Primary Completion Date: Apr 19, 2017
• Actual Study Completion Date: Apr 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DS-5565 Participants receive 15 mg DS-5565 administered once or twice daily. Each participant's dose can be titrated up or down based on the investigator's decision. Analysis will be based on the dose modality at the time of data collection.	Drug: DS-5565; DS-5565 15 mg tablet for oral administration; Other Names: Investigational product

Outcome Measures

Primary Outcome Measures

1. Average Daily Pain Score (ADPS) for DS-5565 [Day 0 (baseline) up to to Week 52 postdose]

   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.

Secondary Outcome Measures

1. 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 [Week 52 postdose]

   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.

2. Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 [Day 0 (baseline) up to Week 52 postdose]

   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.

3. EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 [Day 0 (baseline) up to Week 52 postdose]

   The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) 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.

4. Short Form-36 (SF-36) Measure for DS-5565 [Day 0 (baseline) to Week 52 postdose]

   The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 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.

5. Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 [Day 0 (baseline) up to Week 52 postdose]

   Pain-associated sleep interference was assessed using electronic daily diaries using an 11-point numeric rating scale (NRS) for pain, ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep, unable to sleep). ADSIS is the mean value of all available recordings of the respective week. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able to give written informed consent

• Completed participation (i.e. completed the End-of-Tapering visit) in a preceding study of DS 5565 in FM (DS5565-A-E309, DS5565-A-E310, or DS5565-A-E311)

• Women of child-bearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during the study and for 4 weeks after study completion

• Able to complete subject-reported questionaires per the investigator's judgement

• The subject must not have experienced any significant safety issues during the preceding study that, in the investigator's judgment, would adversely impact the subject's well-being in the long-term extension

De Novo Subjects

• Age ≥ 18 years

• Able to give written informed consent

• Able to complete subject-reported questionnaires per the investigator's judgment

• At screening, subjects must meet the 1990 American College of Rheumatology (ACR) criteria for FM, i.e. widespread pain present for at least 3 months and pain in at least 11 of 18 specific tender point sites. In addition, the 2010 ACR criteria must be met:

• Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5, or WPI 3 to 6 and SS scale score ≥ 9

• Symptoms have been present at a similar level for at least 3 months

• The subject does not have a disorder that would otherwise explain the pain

• ADPS of ≥ 4 on the 11-point numeric rating scale (NRS) over the past 7 days prior to first dose (based on completion of at least 4 daily pain diaries during the 7-day baseline period)

• Subject must have documented evidence of a fundoscopic examination (with pupil dilation) within 12 months prior to screening or at screening

• Women of child-bearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during the study and for 4 weeks after study completion

Exclusion Criteria:

• Clinically significant unstable neurologic, psychiatric, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (e.g. severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) or any other concurrent disease during the preceding study (for rollover subjects) or within 12 months prior to screening (for de novo subjects) that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability

• Subjects who are at risk of suicide as defined by their responses to the C-SSRS or in the opinion of the investigator.

• Subjects with severe or uncontrolled depression that, in the judgment of the investigator, makes the subject inappropriate for entry into the study

• Subjects with pain due to other conditions (e.g. DPNP or post-herpetic neuralgia) that, in the opinion of the investigator, would confound assessment or self-evaluation of the pain associated with FM

• Subjects with pain due to any widespread inflammatory musculoskeletal disorder (e.g. rheumatoid arthritis, lupus) or widespread rheumatic disease other than FM.

• Abuse or dependence of prescription medications, street drugs, or alcohol within the last 1 year

• A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months

• Known hypersensitivity to α2δ ligands or other components of the study medications

• Pregnancy or breast-feeding, or intent to become pregnant during the study period

• Abnormal investigative tests (i.e. ECGs) and laboratory values judged by the investigator to be clinically significant at the End-of-Treatment visit (Visit - Week

1. in the preceding study (for rollover subjects) or at screening (for de novo subjects), with particular focus on:

For De Novo Subjects Only

• Unable to undergo pre-study washout of prohibited concomitant medications (as listed in Section 5.2.1 of the protocol)

• Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) interview (Version 6.0) at screening are excluded, but mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study

• Any diagnosis of lifetime bipolar disorder or psychotic disorder

• Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents

• Subject is an employee of the study center, an immediate family member* of an employee of the study center, or an employee of Daiichi Sankyo, INC Research, or any of the study vendors supporting this study. *(spouse, parent, child, or sibling, whether biological or legally adopted)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States	35242
2		Mobile	Alabama	United States	36608
3		Phoenix	Arizona	United States	85018
4		Anaheim	California	United States	92801
5		Fresno	California	United States	93710
6		Fresno	California	United States	93720
7		Los Alamitos	California	United States	90720
8		Los Angeles	California	United States	90036
9		Newport Beach	California	United States	92660
10		Rancho Mirage	California	United States	92270
11		Roseville	California	United States	95661
12		San Diego	California	United States	92103
13		Santa Ana	California	United States	92705
14		Santa Barbara	California	United States	93108
15		Santa Monica	California	United States	90404
16		Spring Valley	California	United States	91978
17		Thousand Oaks	California	United States	91360
18		Tustin	California	United States	92780
19		Walnut Creek	California	United States	94598
20		Cromwell	Connecticut	United States	06416
21		Bradenton	Florida	United States	34201
22		Brandon	Florida	United States	33511
23		Brooksville	Florida	United States	34601
24		Clearwater	Florida	United States	33761
25		Clearwater	Florida	United States	33765
26		Coral Springs	Florida	United States	33067
27		Fort Lauderdale	Florida	United States	33308
28		Fort Myers	Florida	United States	33912
29		Hialeah	Florida	United States	33013
30		Jacksonville	Florida	United States	32256
31		Kissimmee	Florida	United States	34744
32		Lakeland	Florida	United States	33805
33		Leesburg	Florida	United States	34748
34		Miami	Florida	United States	33140
35		New Port Richey	Florida	United States	34652
36		Ocala	Florida	United States	34471
37		Orlando	Florida	United States	32801
38		Ormond Beach	Florida	United States	32174
39		Royal Palm Beach	Florida	United States	33411
40		Saint Petersburg	Florida	United States	33709
41		Sunrise	Florida	United States	33351
42		Tampa	Florida	United States	33606
43		Alpharetta	Georgia	United States	30005
44		Atlanta	Georgia	United States	30342
45		Columbus	Georgia	United States	31909
46		Savannah	Georgia	United States	31405
47		Smyrna	Georgia	United States	30080
48		Bolingbrook	Illinois	United States	60490
49		Chicago	Illinois	United States	60634
50		Gurnee	Illinois	United States	60031
51		Melrose Park	Illinois	United States	60160
52		Oak Brook	Illinois	United States	60523
53		Evansville	Indiana	United States	47714
54		Indianapolis	Indiana	United States	46260
55		West Des Moines	Iowa	United States	50265
56		Newton	Kansas	United States	67114
57		Shawnee Mission	Kansas	United States	66218
58		Wichita	Kansas	United States	67205
59		Wichita	Kansas	United States	67207
60		Lexington	Kentucky	United States	40509
61		Paducah	Kentucky	United States	42003
62		Lake Charles	Louisiana	United States	70601
63		Boston	Massachusetts	United States	02131
64		Fall River	Massachusetts	United States	02720
65		New Bedford	Massachusetts	United States	02740
66		Watertown	Massachusetts	United States	02472
67		Biloxi	Mississippi	United States	39531
68		Hazelwood	Missouri	United States	63042
69		Kansas City	Missouri	United States	64114
70		Saint Louis	Missouri	United States	63141
71		Springfield	Missouri	United States	65807
72		Billings	Montana	United States	59102
73		Omaha	Nebraska	United States	68114
74		Las Vegas	Nevada	United States	89123
75		Berlin	New Jersey	United States	08009
76		Blackwood	New Jersey	United States	08012
77		Albuquerque	New Mexico	United States	87109
78		Brooklyn	New York	United States	11230
79		Manhasset	New York	United States	11030
80		New York	New York	United States	10168
81		North Massapequa	New York	United States	11758
82		Charlotte	North Carolina	United States	28210
83		Greensboro	North Carolina	United States	27408
84		High Point	North Carolina	United States	27262
85		Raleigh	North Carolina	United States	27612
86		Winston-Salem	North Carolina	United States	27103
87		Fargo	North Dakota	United States	58103
88		Cincinnati	Ohio	United States	45242
89		Dayton	Ohio	United States	45417
90		Kettering	Ohio	United States	45429
91		Tiffin	Ohio	United States	44863
92		Willoughby	Ohio	United States	44094
93		Oklahoma City	Oklahoma	United States	73103
94		Tulsa	Oklahoma	United States	74104
95		Eugene	Oregon	United States	97404
96		Medford	Oregon	United States	97504
97		Portland	Oregon	United States	97210
98		Salem	Oregon	United States	97301
99		Tipton	Pennsylvania	United States	16684
100		Wyomissing	Pennsylvania	United States	19610
101		Anderson	South Carolina	United States	29621
102		Fountain Inn	South Carolina	United States	29644
103		Greer	South Carolina	United States	29651
104		Dakota Dunes	South Dakota	United States	57049
105		Rapid City	South Dakota	United States	57702
106		Knoxville	Tennessee	United States	37919
107		New Tazewell	Tennessee	United States	37836
108		Tullahoma	Tennessee	United States	37388
109		Dallas	Texas	United States	75230
110		Lubbock	Texas	United States	79424
111		Plano	Texas	United States	75093
112		San Antonio	Texas	United States	78232
113		Salt Lake City	Utah	United States	84102
114		Virginia Beach	Virginia	United States	23454
115		Bellevue	Washington	United States	98007
116		Seattle	Washington	United States	98104
117		Wenatchee	Washington	United States	98801
118		Camperdown	New South Wales	Australia
119		Campsie	New South Wales	Australia
120		Coffs Harbour	New South Wales	Australia
121		St. Leonards	New South Wales	Australia
122		Maroochydore	Queensland	Australia
123		Sherwood	Queensland	Australia	4075
124		Sherwood	Queensland	Australia
125		Southport	Queensland	Australia
126		Woodville	South Australia	Australia
127		Hobart	Tasmania	Australia
128		Clayton	Victoria	Australia
129		Malvern East	Victoria	Australia
130		Klagenfurt		Austria
131		Senftenberg		Austria
132		Vienna		Austria	1090
133		Burgas		Bulgaria
134		Pleven		Bulgaria
135		Plovdiv		Bulgaria
136		Ruse		Bulgaria
137		Sevlievo		Bulgaria
138		Sofia		Bulgaria
139		Targovishte		Bulgaria
140		Varna		Bulgaria
141		Penticton	British Columbia	Canada
142		Vancouver	British Columbia	Canada
143		Winnipeg	Manitoba	Canada
144		Burlington	Ontario	Canada
145		Kitchener	Ontario	Canada
146		London	Ontario	Canada
147		Markham	Ontario	Canada	L3R 9W9
148		Markham	Ontario	Canada
149		Mississauga	Ontario	Canada
150		Newmarket	Ontario	Canada
151		Oshawa	Ontario	Canada
152		Sarnia	Ontario	Canada	N7T 4X3
153		Sarnia	Ontario	Canada
154		Toronto	Ontario	Canada	M3J 2C5
155		Toronto	Ontario	Canada
156		Pointe-claire	Quebec	Canada	H9R 3J1
157		Quebec City	Quebec	Canada
158		Sherbrooke	Quebec	Canada
159		Antofagasta	Region 11	Chile
160		Puerto Varas	Region X	Chile
161		Chocen		Czechia
162		Pilsen		Czechia
163		Prague		Czechia
164		Ricany		Czechia
165		Rychnov nad Kneznou		Czechia
166		Aalborg		Denmark
167		Odense		Denmark
168		Tallinn		Estonia
169		Tartu		Estonia
170		Hyvinkaa		Finland
171		Kuopio		Finland
172		Saint Etienne	Cedex	France
173		Douai	Nord	France
174		Elancourt		France
175		Berlin		Germany
176		Bohlen		Germany
177		Dresden		Germany
178		Hannover		Germany
179		Leipzig		Germany
180		Magdeburg		Germany
181		Mainz		Germany
182		Stadtroda		Germany
183		Balassagyarmat		Hungary
184		Budapest		Hungary
185		Debrecen		Hungary
186		Nyiregyhaza		Hungary
187		Baldone		Latvia
188		Balvi		Latvia
189		Jekabpils		Latvia
190		Liepaja		Latvia
191		Ogre		Latvia
192		Riga		Latvia
193		Ventspils		Latvia
194		Kaunas		Lithuania
195		Klaipeda		Lithuania
196		Vilnius		Lithuania
197		Auckland		New Zealand
198		Hamilton		New Zealand
199		Nelson		New Zealand
200		Tauranga		New Zealand
201		Wellington		New Zealand
202		Alesund		Norway
203		Hamar		Norway
204		Hønefoss		Norway
205		Klofta		Norway
206		Lillehammer		Norway
207		Stavanger		Norway
208		Elblag		Poland
209		Gdansk		Poland
210		Katowice		Poland
211		Kraków		Poland
212		Lublin		Poland
213		Nadarzyn		Poland
214		Nowa Sol		Poland
215		Torun		Poland
216		Tychy		Poland
217		Warsaw		Poland
218		Wroclaw		Poland
219		Aveiro		Portugal
220		Guimaraes		Portugal
221		Porto		Portugal
222		Vila Nova de Gaia		Portugal
223		Ponce		Puerto Rico	00716
224		San Juan		Puerto Rico	00909
225		Bacau		Romania
226		Bucharest		Romania
227		Targu Mures		Romania
228		Krasnoyarsk		Russian Federation
229		Moscow		Russian Federation
230		Nizhniy Novgarad		Russian Federation
231		Stavropol		Russian Federation
232		Belgrade		Serbia
233		Banska Bystrica		Slovakia
234		Bratislava		Slovakia
235		Dubnica nad Vahom		Slovakia
236		Galanta		Slovakia
237		Krompachy		Slovakia	05342
238		Piešťany		Slovakia
239		Presov		Slovakia
240		Ljubljana		Slovenia
241		Slovenj Gradec		Slovenia
242		Bayview	Chatsworth	South Africa
243		Johannesburg	Gautang	South Africa
244		Pretoria	Gautang	South Africa
245		Durban	Kwazulu Natal	South Africa
246		Cape Town	Western Cape	South Africa
247		Somerset West	Western Cape	South Africa
248		Stellenbosch		South Africa
249		Santiago de Compostela	A Coruna	Spain
250		Barcelona		Spain
251		Granada		Spain
252		Madrid		Spain
253		Dnipropetrovsk		Ukraine
254		Ivano-Frankivsk		Ukraine
255		Kharkiv		Ukraine
256		Kherson		Ukraine
257		Kyiv		Ukraine
258		Lviv		Ukraine
259		Vinnytsia		Ukraine
260		Zaporizhzhia		Ukraine
261		Penzance	Cornwall	United Kingdom
262		Chesterfield	Derbyshire	United Kingdom
263		Romford	Essex	United Kingdom
264		Manchester	Greater Manchester	United Kingdom
265		Blackpool	Lancashire	United Kingdom
266		Thornton-Cleveleys	Lancashire	United Kingdom
267		Wigan	Lancashire	United Kingdom
268		Stourton	Leeds	United Kingdom
269		Salford	Manchester	United Kingdom
270		Southport	Merseyside	United Kingdom
271		Wellingborough	Northamptonshire	United Kingdom
272		Belfast	Northern Ireland	United Kingdom
273		Cannock	Staffordshire	United Kingdom
274		North Shields	Tyne And Wear	United Kingdom
275		Atherstone	Warwickshire	United Kingdom	CV9 1EU
276		Torpoint		United Kingdom

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 14, 2017

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT02234583
• Other Study ID Numbers: DS5565-A-E312; 2013-005164-26
• First Posted: Sep 9, 2014
• Last Update Posted: Jul 23, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: pain; fibromyalgia
• Additional relevant MeSH terms: Fibromyalgia; Myofascial Pain Syndromes

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	DS-5565 15 mg QD Modal	DS-5565 15 mg BID Modal
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	847	1241
COMPLETED	434	685
NOT COMPLETED	413	556

Baseline Characteristics

Arm/Group Title	DS-5565 15 mg QD Modal	DS-5565 15 mg BID Modal	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	847	1241	2088
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	750 88.5%	1128 90.9%	1878 89.9%
>=65 years	97 11.5%	113 9.1%	210 10.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (11.18)	49.3 (11.94)	50.2 (11.68)
Sex: Female, Male (Count of Participants)
Female	770 90.9%	1130 91.1%	1900 91%
Male	77 9.1%	111 8.9%	188 9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 0.5%	4 0.3%	8 0.4%
Asian	2 0.2%	5 0.4%	7 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	82 9.7%	113 9.1%	195 9.3%
White	740 87.4%	1101 88.7%	1841 88.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	19 2.2%	18 1.5%	37 1.8%
Region of Enrollment (participants) [Number]
United States	569 67.2%	913 73.6%	1879 90%
Czechia	11 1.3%	27 2.2%	38 1.8%
Portugal	0 0%	4 0.3%	4 0.2%
Russia	10 1.2%	1 0.1%	11 0.5%
Austria	5 0.6%	10 0.8%	15 0.7%
Latvia	11 1.3%	8 0.6%	19 0.9%
Poland	16 1.9%	24 1.9%	40 1.9%
Slovakia	14 1.7%	4 0.3%	18 0.9%
Slovenia	4 0.5%	3 0.2%	7 0.3%
Bulgaria	14 1.7%	6 0.5%	20 1%
Chile	1 0.1%	4 0.3%	5 0.2%
France	4 0.5%	2 0.2%	6 0.3%
Lithuania	3 0.4%	1 0.1%	4 0.2%
Serbia	0 0%	3 0.2%	3 0.1%
Romania	3 0.4%	1 0.1%	4 0.2%
Hungary	6 0.7%	1 0.1%	7 0.3%
Ukraine	73 8.6%	59 4.8%	264 12.6%
United Kingdom	14 1.7%	27 2.2%	41 2%
Spain	8 0.9%	19 1.5%	27 1.3%
New Zealand	7 0.8%	11 0.9%	18 0.9%
Canada	17 2%	35 2.8%	52 2.5%
Norway	12 1.4%	30 2.4%	42 2%
Finland	0 0%	1 0.1%	1 0%
Denmark	7 0.8%	5 0.4%	12 0.6%
South Africa	9 1.1%	10 0.8%	38 1.8%
Australia	5 0.6%	8 0.6%	13 0.6%
Germany	22 2.6%	16 1.3%	38 1.8%
Estonia	2 0.2%	8 0.6%	10 0.5%

Outcome Measures

1. Primary Outcome

Title	Average Daily Pain Score (ADPS) for DS-5565
Description	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.
Time Frame	Day 0 (baseline) up to to Week 52 postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rollover DS-5565 15 mg QD Modal	Rollover DS-5565 15 mg BID Modal	De Novo DS-5565 15 mg QD Modal	De Novo DS-5565 15 mg BID Modal
Arm/Group Description	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.	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.	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.	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.
Measure Participants	578	962	269	279
Baseline	4.77 (2.23)	5.58 (2.22)	7.08 (1.40)	7.38 (1.37)
Week 13	3.47 (2.11)	4.36 (2.32)	3.21 (2.20)	4.06 (2.37)
Week 24	3.28 (2.08)	4.24 (2.35)	3.0 (2.14)	4.0 (2.38)
Week 36	3.20 (2.06)	4.25 (2.34)	2.74 (2.23)	3.95 (2.59)
Week 48	3.22 (2.16)	4.25 (2.37)	2.46 (2.15)	3.80 (2.61)
Week 52	3.20 (2.18)	4.26 (2.42)	2.31 (1.94)	3.80 (2.70)

2. Secondary Outcome

Title	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
Description	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.
Time Frame	Week 52 postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rollover DS-5565 15 mg QD Modal	Rollover DS-5565 15 mg BID Modal	De Novo DS-5565 15 mg QD Modal	De Novo DS-5565 15 mg BID Modal
Arm/Group Description	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.	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.	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.	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.
Measure Participants	578	962	269	279
Count of Participants [Participants]	208 24.6%	333 26.8%	96 4.6%	92 NaN

3. Secondary Outcome

Title	Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565
Description	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.
Time Frame	Day 0 (baseline) up to Week 52 postdose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rollover DS-5565 15 mg QD Modal	Rollover DS-5565 15 mg BID Modal	De Novo DS-5565 15 mg QD Modal	De Novo DS-5565 15 mg QID Modal
Arm/Group Description	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. DS-5565: DS-5565 15 mg tablet for oral administration	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. DS-5565: DS-5565 15 mg tablet for oral administration	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. DS-5565: DS-5565 15 mg tablet for oral administration	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. DS-5565: DS-5565 15 mg tablet for oral administration
Measure Participants	578	962	269	279
Anxiety Subscale Baseline	5.7 (3.86)	7.2 (4.05)	6.9 (3.97)	7.4 (4.21)
Anxiety Subscale Week 52	4.8 (3.71)	7.0 (4.03)	4.4 (3.29)	5.7 (3.88)
Depression Subscale Baseline	5.1 (4.18)	6.3 (4.34)	5.6 (4.06)	5.7 (4.10)
Depression Subscale Week 52	3.5 (3.47)	4.8 (4.01)	2.8 (3.11)	3.9 (4.00)

4. Secondary Outcome

Title	EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565
Description	The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) 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.
Time Frame	Day 0 (baseline) up to Week 52 postdose

Outcome Measure Data

Analysis Population Description

EQ-5D was assessed in the Safety Analysis Set.

Arm/Group Title	Rollover DS-5565 15 mg QD Modal	Rollover DS-5565 15 mg BID Modal	De Novo DS-5565 15 mg QD Modal	De Novo DS-5565 15 mg BID Modal
Arm/Group Description	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.	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.	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.	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.
Measure Participants	578	962	269	279
Total Score Baseline	0.70 (0.17)	0.64 (0.19)	0.62 (0.16)	0.61 (0.18)
Total Score Week 52	0.76 (0.16)	0.70 (0.20)	0.81 (0.15)	0.77 (0.17)

5. Secondary Outcome

Title	Short Form-36 (SF-36) Measure for DS-5565
Description	The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 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.
Time Frame	Day 0 (baseline) to Week 52 postdose

Outcome Measure Data

Analysis Population Description

SF-36 was assessed in the Safety Analysis Set.

Arm/Group Title	Rollover DS-5565 15 mg QD Modal	Rollover DS-5565 15 mg BID Modal	De Novo DS-5565 15 mg QD Modal	De Novo DS-5565 15 mg BID Modal
Arm/Group Description	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.	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.	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.	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.
Measure Participants	578	962	269	279
Physical Component Summary Baseline	37.91 (8.86)	35.13 (8.55)	34.41 (8.58)	32.12 (7.85)
Physical Component Summary Week 52	42.96 (8.52)	39.09 (9.38)	45.61 (9.63)	42.31 (10.47)
Mental Component Summary Baseline	50.12 (10.19)	47.76 (11.15)	47.54 (10.98)	47.92 (11.46)
Mental Component Summary Week 52	52.63 (9.61)	49.15 (11.24)	52.75 (8.02)	50.49 (10.54)

6. Secondary Outcome

Title	Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565
Description	Pain-associated sleep interference was assessed using electronic daily diaries using an 11-point numeric rating scale (NRS) for pain, ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep, unable to sleep). ADSIS is the mean value of all available recordings of the respective week. 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.
Time Frame	Day 0 (baseline) up to Week 52 postdose

Outcome Measure Data

Analysis Population Description

Average Daily Sleep Interference Score was assessed in the Safety Analysis Set.

Arm/Group Title	Rollover DS-5565 15 mg QD Modal	Rollover DS-5565 15 mg BID Modal	De Novo DS-5565 15 mg QD Modal	De Novo DS-5565 15 mg BID Modal
Arm/Group Description	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.	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.	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.	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.
Measure Participants	578	962	269	279
Baseline	3.84 (2.41)	4.74 (2.52)	6.71 (1.70)	6.82 (1.82)
Week 13	2.56 (2.16)	3.18 (2.50)	2.50 (2.15)	3.13 (2.51)
Week 24	2.34 (1.96)	3.09 (2.50)	2.36 (2.18)	3.19 (2.48)
Week 36	2.25 (1.98)	3.09 (2.50)	2.19 (2.20)	3.11 (2.63)
Week 48	2.32 (2.07)	3.22 (2.56)	1.87 (2.05)	3.02 (2.64)
Week 52	2.22 (2.06)	3.19 (2.63)	1.79 (1.86)	3.09 (2.71)

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) were collected from baseline up to 4 weeks after last dose, up to 2 years 3 months.
Adverse Event Reporting Description	A TEAE was any adverse event that emerged on or after the first dosing of 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.
Arm/Group Title	DS-5565 15 mg QD Modal		DS-5565 15 mg BID Modal
Arm/Group Description	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.		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.
All Cause Mortality
	DS-5565 15 mg QD Modal		DS-5565 15 mg BID Modal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/847 (0.4%)		2/1241 (0.2%)
Serious Adverse Events
	DS-5565 15 mg QD Modal		DS-5565 15 mg BID Modal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/847 (4.8%)		94/1241 (7.6%)
Cardiac disorders
Cardiac failure congestive	1/847 (0.1%)		1/1241 (0.1%)
Coronary artery disease	0/847 (0%)		2/1241 (0.2%)
Acute myocardial infarction	0/847 (0%)		1/1241 (0.1%)
Angina pectoris	0/847 (0%)		1/1241 (0.1%)
Myocardial infarction	1/847 (0.1%)		0/1241 (0%)
Supraventricular tachycardia	0/847 (0%)		1/1241 (0.1%)
Congenital, familial and genetic disorders
Spine malformation	0/847 (0%)		1/1241 (0.1%)
Ear and labyrinth disorders
Vertigo	1/847 (0.1%)		1/1241 (0.1%)
Gastrointestinal disorders
Gastritis	0/847 (0%)		2/1241 (0.2%)
Abdominal pain upper	0/847 (0%)		1/1241 (0.1%)
Diverticulum	0/847 (0%)		1/1241 (0.1%)
Incarcerated umbilical hernia	0/847 (0%)		1/1241 (0.1%)
Intestinal perforation	0/847 (0%)		1/1241 (0.1%)
Pancreatitis	0/847 (0%)		1/1241 (0.1%)
General disorders
Non-cardiac chest pain	1/847 (0.1%)		4/1241 (0.3%)
Oedema peripheral	0/847 (0%)		2/1241 (0.2%)
Asthenia	0/847 (0%)		1/1241 (0.1%)
Chest discomfort	0/847 (0%)		1/1241 (0.1%)
Death	0/847 (0%)		1/1241 (0.1%)
Pyrexia	0/847 (0%)		1/1241 (0.1%)
Hepatobiliary disorders
Cholecystitis	1/847 (0.1%)		1/1241 (0.1%)
Cholecystitis acute	0/847 (0%)		1/1241 (0.1%)
Cholecystitis chronic	1/847 (0.1%)		0/1241 (0%)
Cholelithiasis	0/847 (0%)		1/1241 (0.1%)
Infections and infestations
Appendicitis	3/847 (0.4%)		1/1241 (0.1%)
Gastroenteritis	0/847 (0%)		2/1241 (0.2%)
Pneumonia	1/847 (0.1%)		1/1241 (0.1%)
Urinary tract infection	0/847 (0%)		2/1241 (0.2%)
Abscess limb	0/847 (0%)		1/1241 (0.1%)
Chronic hepatitis C	0/847 (0%)		1/1241 (0.1%)
Cystitis	0/847 (0%)		1/1241 (0.1%)
Diverticulitis	0/847 (0%)		1/1241 (0.1%)
Gastroenteritis salmonella	0/847 (0%)		1/1241 (0.1%)
Infectious colitis	0/847 (0%)		1/1241 (0.1%)
Influenza	0/847 (0%)		1/1241 (0.1%)
Localised infection	0/847 (0%)		1/1241 (0.1%)
Meningitis aseptic	1/847 (0.1%)		0/1241 (0%)
Septic shock	0/847 (0%)		1/1241 (0.1%)
Sinusitis	0/847 (0%)		1/1241 (0.1%)
Viral upper respiratory tract infection	0/847 (0%)		1/1241 (0.1%)
Injury, poisoning and procedural complications
Femur fracture	1/847 (0.1%)		1/1241 (0.1%)
Road traffic accident	0/847 (0%)		2/1241 (0.2%)
Acetabulum fracture	0/847 (0%)		1/1241 (0.1%)
Anaesthetic complication	0/847 (0%)		1/1241 (0.1%)
Burns third degree	0/847 (0%)		1/1241 (0.1%)
Fall	0/847 (0%)		1/1241 (0.1%)
Fibula fracture	0/847 (0%)		1/1241 (0.1%)
Foot fracture	0/847 (0%)		1/1241 (0.1%)
Hand fracture	1/847 (0.1%)		0/1241 (0%)
Head injury	0/847 (0%)		1/1241 (0.1%)
Humerous fracture	0/847 (0%)		1/1241 (0.1%)
Meniscus injury	0/847 (0%)		1/1241 (0.1%)
Overdose	0/847 (0%)		1/1241 (0.1%)
Periprosthetic fracture	1/847 (0.1%)		0/1241 (0%)
Radius fracture	0/847 (0%)		1/1241 (0.1%)
Rib fracture	0/847 (0%)		1/1241 (0.1%)
Seroma	0/847 (0%)		1/1241 (0.1%)
Tibia fracture	0/847 (0%)		1/1241 (0.1%)
Investigations
Hepatic enzyme increased	2/847 (0.2%)		1/1241 (0.1%)
Aspartate aminotransferase increased	0/847 (0%)		1/1241 (0.1%)
Blood creatinine phosphokinase abnormal	1/847 (0.1%)		0/1241 (0%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/847 (0%)		2/1241 (0.2%)
Dehydration	1/847 (0.1%)		0/1241 (0%)
Diabetic ketoacidosis	0/847 (0%)		1/1241 (0.1%)
Hyponatraemia	0/847 (0%)		1/1241 (0.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/847 (0%)		2/1241 (0.2%)
Back pain	0/847 (0%)		2/1241 (0.2%)
Flank pain	2/847 (0.2%)		0/1241 (0%)
Fibromyalgia	0/847 (0%)		1/1241 (0.1%)
Intervertebral disc protrusion	0/847 (0%)		1/1241 (0.1%)
Musculoskeletal pain	0/847 (0%)		1/1241 (0.1%)
Osteoarthritis	0/847 (0%)		1/1241 (0.1%)
Spinal column stenosis	0/847 (0%)		1/1241 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma	2/847 (0.2%)		1/1241 (0.1%)
Breast cancer	0/847 (0%)		2/1241 (0.2%)
Renal cell carcinoma	0/847 (0%)		2/1241 (0.2%)
B-cell lymphoma	1/847 (0.1%)		0/1241 (0%)
Breast cancer stage III	1/847 (0.1%)		0/1241 (0%)
Castleman's disease	0/847 (0%)		1/1241 (0.1%)
Fibroadenoma of breast	0/847 (0%)		1/1241 (0.1%)
Lung neoplasm	0/847 (0%)		1/1241 (0.1%)
Lung neoplasm malignant	0/847 (0%)		1/1241 (0.1%)
Lymphoma	0/847 (0%)		1/1241 (0.1%)
Malignant melanoma	0/847 (0%)		1/1241 (0.1%)
Pancreatic carcinoma metastatic	0/847 (0%)		1/1241 (0.1%)
Uterine cancer	1/847 (0.1%)		0/1241 (0%)
Nervous system disorders
Convulsion	0/847 (0%)		3/1241 (0.2%)
Dizziness	2/847 (0.2%)		0/1241 (0%)
Headache	1/847 (0.1%)		1/1241 (0.1%)
Syncope	1/847 (0.1%)		1/1241 (0.1%)
Altered state of consciousness	0/847 (0%)		1/1241 (0.1%)
Cerebrovascular accident	0/847 (0%)		1/1241 (0.1%)
Chronic inflammatory demyelinating polyradiculoneuropathy	1/847 (0.1%)		0/1241 (0%)
Dysarthria	0/847 (0%)		1/1241 (0.1%)
Generalised tonic-clonic seizure	0/847 (0%)		1/1241 (0.1%)
Ischaemic stroke	0/847 (0%)		1/1241 (0.1%)
Loss of consciousness	1/847 (0.1%)		0/1241 (0%)
Migraine	1/847 (0.1%)		0/1241 (0%)
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum	0/847 (0%)		1/1241 (0.1%)
Psychiatric disorders
Suicidal ideation	3/847 (0.4%)		3/1241 (0.2%)
Suicide attempt	3/847 (0.4%)		0/1241 (0%)
Depression	1/847 (0.1%)		1/1241 (0.1%)
Major depression	0/847 (0%)		1/1241 (0.1%)
Suicidal behaviour	0/847 (0%)		1/1241 (0.1%)
Renal and urinary disorders
Renal failure acute	0/847 (0%)		2/1241 (0.2%)
Haematuria	0/847 (0%)		1/1241 (0.1%)
Nephrolithiasis	0/847 (0%)		1/1241 (0.1%)
Reproductive system and breast disorders
Ovarian cyst	0/847 (0%)		2/1241 (0.2%)
Endometrial hyperplasia	1/847 (0.1%)		0/1241 (0%)
Uterine polyp	0/847 (0%)		1/1241 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	2/847 (0.2%)		1/1241 (0.1%)
Dysphonia	1/847 (0.1%)		0/1241 (0%)
Dyspnoea	0/847 (0%)		1/1241 (0.1%)
Pulmonary embolism	1/847 (0.1%)		0/1241 (0%)
Social circumstances
Bereavement	0/847 (0%)		1/1241 (0.1%)
Vascular disorders
Hypertension	1/847 (0.1%)		1/1241 (0.1%)
Aortic stenosis	0/847 (0%)		1/1241 (0.1%)
Blood pressure fluctuation	0/847 (0%)		1/1241 (0.1%)
Peripheral venous disease	0/847 (0%)		1/1241 (0.1%)
Other (Not Including Serious) Adverse Events
	DS-5565 15 mg QD Modal		DS-5565 15 mg BID Modal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	669/847 (79%)		1056/1241 (85.1%)
Eye disorders
Vision blurred	26/847 (3.1%)		56/1241 (4.5%)
Gastrointestinal disorders
Nausea	61/847 (7.2%)		113/1241 (9.1%)
Diarrhoea	40/847 (4.7%)		97/1241 (7.8%)
General disorders
Drug withdrawal syndrome	61/847 (7.2%)		135/1241 (10.9%)
Fatigue	76/847 (9%)		83/1241 (6.7%)
Oedema peripheral	52/847 (6.1%)		82/1241 (6.6%)
Infections and infestations
Upper respiratory tract infection	43/847 (5.1%)		134/1241 (10.8%)
Urinary tract infection	51/847 (6%)		107/1241 (8.6%)
Nasopharyngitis	47/847 (5.5%)		110/1241 (8.9%)
Sinusitis	36/847 (4.3%)		89/1241 (7.2%)
Investigations
Weight increased	83/847 (9.8%)		207/1241 (16.7%)
Musculoskeletal and connective tissue disorders
Back pain	35/847 (4.1%)		89/1241 (7.2%)
Arthralgia	32/847 (3.8%)		88/1241 (7.1%)
Pain in extremity	27/847 (3.2%)		64/1241 (5.2%)
Fibromyalgia	26/847 (3.1%)		62/1241 (5%)
Nervous system disorders
Dizziness	134/847 (15.8%)		148/1241 (11.9%)
Headache	123/847 (14.5%)		158/1241 (12.7%)
Somnolence	130/847 (15.3%)		102/1241 (8.2%)
Psychiatric disorders
Insomnia	34/847 (4%)		63/1241 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.