Treatment of Pain Associated With Fibromyalgia | NCT02146430

ID	Type	Description	Link
2013-005161-40	EudraCT Number

Name	Class
Syneos Health	OTHER

Label	Type	Description	Intervention Names
DS-5565 QD	Experimental	Participants take one each of placebo tablet and capsule in the morning, and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening	Drug: DS-5565 Drug: Placebo tablet Drug: Placebo capsule
DS-5565 BID	Experimental	Participants take one DS-5565 tablet and one placebo capsule, twice daily (BID)	Drug: DS-5565 Drug: Placebo capsule
Pregabalin	Active Comparator	Participants take one pregabalin capsule and one placebo tablet BID	Drug: Pregabalin Drug: Placebo tablet
Placebo	Placebo Comparator	Participants take one each of placebo tablet and capsule BID	Drug: Placebo tablet Drug: Placebo capsule

Name	Type	Description	Arm Group Labels	Other Names
DS-5565	Drug	DS-5565 15 mg tablet for oral administration	DS-5565 BID DS-5565 QD

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Weekly Average Daily Pain Score (ADPS) at Week 13 in Participants Receiving DS-5565, Pregabalin, Placebo	Average daily pain scores (ADPS) reported by the participant that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale where 0 = no pain to 10 = worst possible pain. Higher scores indicate a worse outcome. For participants with no Week 13 data, the baseline observation was carried forward (BOCF). The mean (multiple imputation estimate) and standard error (multiple imputation) are reported.	Baseline up to Week 13 postdose

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Who Answered "Much Improved or Better" in Patient Global Impression of Change (PGIC) at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo	Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. Higher scores indicate worse outcomes. The number of participants with 'much improved or better' status (≤2) is being reported.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥ 18 years
Able to give written informed consent
Able to complete participant-reported questionnaires per the investigator's judgment
At screening, participants must meet the 1990 American College of Rheumatology (ACR) criteria for fibromyalgia (FM), i.e. widespread pain present for at least 3 months and pain in at least 11 of 18 specific tender point sites. In addition, the 2010 ACR criteria must be met:
Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5, or WPI 3 to 6 and SS scale score ≥ 9
Symptoms have been present at a similar level for at least 3 months
The subject does not have a disorder that would otherwise explain the pain
ADPS of ≥ 4 on the 11-point numeric rating scale (NRS) over the past 7 days prior to randomization (based on completion of at least 4 daily pain diaries during the 7-day baseline period prior to randomization)
Subject must have documented evidence of a fundoscopic examination (with pupil dilation) within 12 months prior to screening or at screening.
Women of child-bearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during the study and for 4 weeks after study completion.

Exclusion Criteria:

Clinically significant unstable neurologic, psychiatric, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (e.g. severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) or any other concurrent disease within 12 months prior to screening that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability
Anticipation of initiation or significant change to normal daily exercise routines or need for ongoing use of concomitant medications or non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety
Unable to undergo pre-study washout of prohibited concomitant medications
Subjects who are at risk of suicide as defined by their responses to the Columbia-Suicide Severity Rating Scale (C-SSRS) or in the opinion of the investigator. Note: Patients answering "yes" to any of the questions about active suicidal ideation/intent/behaviors occurring within the past 12 months must be excluded (C-SSRS Suicide Ideation section - Questions 3, 4, or 5; C-SSRS Suicidal Behavior section, any of the suicide behaviors questions). Such patients should be referred immediately to a mental health professional for appropriate evaluation.
Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study.
Any diagnosis of lifetime bipolar disorder or psychotic disorder
Participants with pain due to other conditions (e.g. diabetic peripheral neuropathic pain or post-herpetic neuralgia) that in the opinion of the investigator, would confound assessment or self-evaluation of the pain associated with FM.
Participants with pain due to any widespread inflammatory musculoskeletal disorder (e.g. rheumatoid arthritis, lupus) or widespread rheumatic disease other than FM.
Abuse or dependence of prescription medications, street drugs, or alcohol within the last 1 year
Any history of a malignancy other than basal cell carcinoma within the past 5 years
A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months
Pregnancy or breast-feeding, or intent to become pregnant during the study period
Participant is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents.
Known hypersensitivity to alpha2-delta (α2δ) ligands or other components of the study medications. Note: Prior exposure to DS-5565 is allowed, as long as hypersensitivity to DS-5565 was not observed.
Participants who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the investigator to be unlikely to complete the study.
Abnormal investigative tests (i.e. electrocardiograms [ECGs]) and laboratory values judged by the investigator to be clinically significant at screening, with particular focus on: a. Abnormal renal function defined as calculated creatinine clearance (CrCl) < 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen> 1.5 × upper limit of normal (ULN); creatine kinase > 3.0 × ULN; serum creatinine > 1.6 mg/dL (> 141.4 μmol/L); b. Abnormal liver function defined as aspartate aminotransferase (AST) > 2.0 × ULN, alanine aminotransferase (ALT) > 2.0 × ULN; alkaline phosphatase > 1.5 × ULN; total bilirubin> 1.2 × ULN. If a subject has total bilirubin > 1.2 ULN, unconjugated and conjugated bilirubin fractions should be analyzed and only participants documented to have Gilbert's syndrome may be enrolled.

Name	Affiliation	Role
Global Clinical Leader	Daiichi Sankyo	Study Director

PubMed Identifier	Type	Citation	Retractions
31284771	Derived	Arnold LM, Whitaker S, Hsu C, Jacobs D, Merante D. Efficacy and safety of mirogabalin for the treatment of fibromyalgia: results from three 13-week randomized, double-blind, placebo- and active-controlled, parallel-group studies and a 52-week open-label extension study. Curr Med Res Opin. 2019 Oct;35(10):1825-1835. doi: 10.1080/03007995.2019.1629757. Epub 2019 Jul 9.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.
FG001	Pregabalin 150 mg BID	Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Weekly Average Daily Pain Score (ADPS) at Week 13 in Participants Receiving DS-5565, Pregabalin, Placebo

Average daily pain scores (ADPS) reported by the participant that best describes his or her worst pain over the previous 24 hours. A daily pain score has a scale where 0 = no pain to 10 = worst possible pain. Higher scores indicate a worse outcome. For participants with no Week 13 data, the baseline observation was carried forward (BOCF). The mean (multiple imputation estimate) and standard error (multiple imputation) are reported.

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

Posted

Mean

Standard Error

units on a scale

Baseline up to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.
OG001	Pregabalin 150 mg BID	Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.
OG002	DS-5565 15 mg QD	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.
OG003	DS-5565 15 mg BID	Participants who received oral DS-5565 15 mg and pregabalin placebo in the morning and evening.

Units	Counts
Participants	OG000318 OG001317 OG002319 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.66± 0.132 OG001-1.90± 0.134 OG002-1.97± 0.134 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Difference of means		0.1870		Mean Difference (Final Values)	-0.25	Standard Error of the Mean	0.187	2-Sided	95	-0.61	0.12					Superiority
OG000 OG002		Difference of means

Secondary

Number of Participants Who Answered "Much Improved or Better" in Patient Global Impression of Change (PGIC) at Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo

Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. Higher scores indicate worse outcomes. The number of participants with 'much improved or better' status (≤2) is being reported.

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

Posted

Count of Participants

Participants

Baseline up Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.
OG001	Pregabalin 150 mg BID	Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.
OG002	DS-5565 15 mg QD	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.
OG003	DS-5565 15 mg BID

Secondary

Change in Fibromyalgia Index Questionnaire (FIQ) Total Score From Baseline to Week 13 in Participants Receiving DS-5565, Pregabalin, or Placebo

The total FIQ score is composed of 10 items, with a maximum possible score of 100. The first item contains 11 questions related to physical functioning and are rated on a 4-point Likert-type scale, where 0 indicates 'always' and 3 indicates 'never'. The overall impact items are rated on a 0-7 scale for the number of days that the patient felt well and the number of days they were unable to work (including housework) because of fibromyalgia symptoms. The symptoms items are rated on visual analog scales (0-10 cm), with higher numbers indicated greater symptomatology. Scores range from 0 (no impairment) to 10 (maximum impairment), where higher scores indicate worse outcome.

For this outcome, the change in total FIQ score from baseline is being reported. Negative values indicate improvement from baseline in impairment.

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

Posted

Mean

Standard Deviation

units on a scale

Baseline up to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral pregabalin placebo and DS5565 placebo twice daily (BID).
OG001	Pregabalin 150 mg BID	Participants who received oral pregabalin 150 mg twice daily (BID).
OG002

Secondary

Number of Responders at Week 13 Among Participants Receiving DS-5565, Pregabalin, or Placebo

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

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

Posted

Count of Participants

Participants

Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral pregabalin placebo and DS5565 placebo twice daily (BID).
OG001	Pregabalin 150 mg BID	Participants who received oral pregabalin 150 mg twice daily (BID).
OG002	DS-5565 15 mg QD	Participants who received oral DS5565 15 mg once daily (QD).
OG003	DS-5565 15 mg BID	Participants who received DS-5565 15 mg twice daily (BID).

Secondary

Change From Baseline to Week 13 in Multidimensional Fatigue Inventory (MFI-20) General Fatigue Score in Participants Receiving DS-5565, Pregabalin, or Placebo

MFI is a validated 20-item, self-reported instrument designed to measure fatigue in the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. The respondent is asked to mark an 'X' in 1 of 5 boxes arranged linearly where 1 is 'Yes, that is true' and 5 is 'No, that is not true.' Each subscale consists of 4 items, 2 indicative for fatigue and 2 contraindicative. For the indicative questions, a high score indicates a high fatigue level and low scores indicate a low fatigue levels. Conversely, for the contraindicative questions a high score indicates a low fatigue level and a low score indicates a high fatigue level. Overall, respondents are rated on a scale of 0 (no fatigue) to 7 (high fatigue).

For this outcome, the change from baseline in MFI-20 general fatigue subscale score is being reported. Negative values indicate an improvement in fatigue.

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

Posted

Mean

Standard Deviation

units on a scale

Baseline up to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.
OG001	Pregabalin 150 mg BID	Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.

Secondary

Change From Baseline to Week 13 in Hospital Anxiety and Depression Scale (HADS) in Participants Receiving DS-5565, Pregabalin, or Placebo

The HADS questionnaire is a reliable, widely-used self-assessment scale to assess symptoms of anxiety and depression. The instrument consists of 7 questions related to anxiety and 7 related to depression, each rated on a 4-point scale (score of 0 to 3). Scores for anxiety and depression are independently summed to compute HADS Anxiety and HADS-Depression subscale scores, with ranges from 0 (no anxiety/depression) to 21 (most severe anxiety/depression).

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

Posted

Mean

Standard Deviation

units on a scale

Baseline up to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral pregabalin placebo and DS5565 placebo twice daily (BID).
OG001	Pregabalin 150 mg BID	Participants who received oral pregabalin 150 mg twice daily (BID).
OG002	DS-5565 15 mg QD	Participants who received oral DS5565 15 mg once daily (QD).
OG003

Secondary

Change From Baseline to Week 13 in Short Form 36 (SF-36) in Participants Receiving DS-5565, Pregabalin, or Placebo

The SF-36 is a 36-question health survey that measures functional health and well-being from the participant's point of view. It is a measure of physical and mental health used across various disease areas, including fibromyalgia. The SF-36 scale ranges from 0 to 100 where lower scores indicate more disability (worse health) and higher scores represent less disability (better health). The physical component summary (PCS) and mental component summary (MCS) scores are reported.

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

Posted

Mean

Standard Deviation

units on a scale

Baseline up to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral pregabalin placebo and DS5565 placebo twice daily (BID).
OG001	Pregabalin 150 mg BID	Participants who received oral pregabalin 150 mg twice daily (BID).
OG002	DS-5565 15 mg QD	Participants who received oral DS5565 15 mg once daily (QD).
OG003

Secondary

Change From Baseline to Week 13 in EuroQol Five Dimensions Questionnaire (EQ-5D) in Participants Receiving DS-5565, Pregabalin, or Placebo

The EQ-5D is an instrument that shows high construct validity and responsiveness in patients with chronic pain and has been used specifically in fibromyalgia. The EQ-5D includes a descriptive section with 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with a scale that ranges from 0 (no problems) to 5 (extreme problems). These 5 dimensions are combined into an overall health utilities index, and a numeric rating scale (100 mm visual analog scale) that measures perception of overall health, with 0 indicating worst health and 100 representing best imaginable health. A summary index with a maximum total score of 1 can be derived from these five dimensions by conversion with a table of scores. The maximum total score of 1 indicates the best health outcome.

For this outcome, the change from baseline in total EQ-5D score is being reported. Positive values indicate an improvement in health.

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

Posted

Mean

Standard Deviation

units on a scale

Baseline up to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral pregabalin placebo and DS5565 placebo twice daily (BID).
OG001	Pregabalin 150 mg BID	Participants who received oral pregabalin 150 mg twice daily (BID).

Secondary

Change From Baseline to Week 13 in Average Daily Sleep Interference in Participants Receiving DS-5565, Pregabalin, or Placebo

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.

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

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline up Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral pregabalin placebo and DS5565 placebo twice daily (BID).
OG001	Pregabalin 150 mg BID	Participants who received oral pregabalin 150 mg twice daily (BID).
OG002	DS-5565 15 mg QD	Participants who received oral DS5565 15 mg once daily (QD).
OG003	DS-5565 15 mg BID

Secondary

Number of Participants Reporting Optimal Sleep at Week 13 on the Medical Outcomes Study (MOS) Sleep Scale In Participants Receiving DS-5565, Pregabalin, or Placebo

The MOS Sleep Scale is a 12-item questionnaire from which the following subscales were derived: sleep disturbance (4 items), quantity of sleep/optimal sleep (1 item), snoring (1 item), awakening due to shortness of breath or due to headache (1 item), sleep adequacy (2 items), and somnolence (3 items). In addition, values for sleep disturbances index (9 items), optimal sleep scale (1 item), and sleep quantity scale (1 item) were determined. Most subscales range from 0 to 100, where higher scores indicate more of the concept begin measured (eg., higher sleep disturbance scores indicate greater sleep disturbances).

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

Posted

Count of Participants

Participants

Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.
OG001	Pregabalin 150 mg BID	Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.
OG002	DS-5565 15 mg QD

Secondary

Change From Baseline to Week 13 in the Brief Pain Inventory Short Form (BPI-SF) in Participants Receiving DS-5565, Pregabalin, or Placebo

The BPI-SF measures pain severity and interference within the past 24 hours. Items are rated on an 11-point NRS from 0 to 10, where 0 indicates does not interfere and 10 indicates completely interferes. Severity score is the average of the responses to the 4 pain intensity items that assess the Worst/Least/Average pain in the last 24 hours and the Pain Right Now. The individual items being reported (using the same scale as noted above) are Severity, General Activity, Mood, Walking Ability, Normal Work, Relations With Other People, Sleep, and Enjoyment of Life. Percentage relief of treatment pain scale ranges from 100% (complete pain relief) to 0% (no pain relief) and higher percentages indicate better outcome. Interference % is the average of responses for General activity, Mood, Walking ability, Normal work, Relations with other people, Sleep, Enjoyment of life where 0% (no interference) to 100% (completely interferes) and negative (ie. lower) percentages indicate better outcomes.

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

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline up to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral pregabalin placebo and DS5565 placebo twice daily (BID).
OG001	Pregabalin 150 mg BID

Secondary

Proportion of Days a Rescue Medication Was Used Among Participants Receiving DS-5565, Pregabalin, or Placebo

Proportion of days with rescue medication intake during the double-blind treatment period equals number of days with rescue medication intake/(date of last study drug administration in the double-blind treatment period) - (date of first study drug administration + 1).

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

Posted

Mean

Standard Deviation

proportion of days

Week 1 to Week 13 postdose

ID	Title	Description
OG000	Placebo	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and evening.
OG001	Pregabalin 150 mg BID	Participants who received oral DS-5565 placebo and pregabalin 150 mg BID in the morning and evening.
OG002	DS-5565 15 mg QD	Participants who received oral DS-5565 placebo and pregabalin placebo in the morning and DS-5565 15 mg and pregabalin placebo in the evening.
OG003	DS-5565 15 mg BID

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Transaminases increased	Investigations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG0030 events0 affected320 at risk
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0011 events1 affected318 at risk EG0020 events0 affected320 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0021 events1 affected320 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0021 events1 affected320 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Catheter site haemorrhage	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0021 events1 affected320 at risk EG003
Pyrexia	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0021 events1 affected320 at risk EG003
Salivary gland calculus	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Withdrawal syndrome	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0011 events1 affected318 at risk EG0020 events0 affected320 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Postmenopausal haemorrhage	Reproductive system and breast disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0011 events1 affected318 at risk EG0020 events0 affected320 at risk EG003
Calculus ureteric	Renal and urinary disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Back disorder	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Appendicitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Bronchitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0021 events1 affected320 at risk EG003
Infectious colitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Staphylococcal infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected318 at risk EG0010 events0 affected318 at risk EG0021 events1 affected320 at risk EG003
Cellulitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003
Sepsis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected318 at risk EG0010 events0 affected318 at risk EG0020 events0 affected320 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Weight increased	Investigations	MedDRA 17.1	Systematic Assessment	EG00016 events16 affected318 at risk EG00136 events36 affected318 at risk EG00221 events21 affected320 at risk EG00336 events36 affected320 at risk
Dizziness	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG00020 events20 affected318 at risk EG00165 events65 affected318 at risk EG00253 events53 affected320 at risk EG003
Headache	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG00036 events36 affected318 at risk EG00148 events48 affected318 at risk EG00245 events45 affected320 at risk EG003
Somnolence	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0007 events7 affected318 at risk EG00137 events37 affected318 at risk EG00225 events25 affected320 at risk EG003
Fatigue	General disorders	MedDRA 17.1	Systematic Assessment	EG00010 events10 affected318 at risk EG00123 events23 affected318 at risk EG00223 events23 affected320 at risk EG003
Oedema peripheral	General disorders	MedDRA 17.1	Systematic Assessment	EG00011 events11 affected318 at risk EG00119 events19 affected318 at risk EG00214 events14 affected320 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0007 events7 affected318 at risk EG00113 events13 affected318 at risk EG00216 events16 affected320 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG00019 events19 affected318 at risk EG00127 events27 affected318 at risk EG00227 events27 affected320 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0005 events5 affected318 at risk EG00121 events21 affected318 at risk EG00215 events15 affected320 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG00014 events14 affected318 at risk EG00110 events10 affected318 at risk EG00210 events10 affected320 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG00024 events24 affected318 at risk EG00121 events21 affected318 at risk EG00222 events22 affected320 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Glendale	Arizona		United States

ID	Term
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases

ID	Term
D005680	gamma-Aminobutyric Acid
D000613	Aminobutyrates
D002087	Butyrates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	Placebo	Placebo for oral administration matching capsule for DS-5565 and matching tablet for pregabalin
BG001	Pregabalin	Participants take one pregabalin capsule and one placebo tablet BID
BG002	DS-5565 QD	Participants take one each of placebo tablet and capsule in the morning and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening
BG003	DS-5565 BID	Participants take one DS-5565 tablet and one placebo capsule BID
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo for oral administration matching capsule for DS-5565 and matching tablet for pregabalin	318	11	318	145	318
EG001	Pregabalin	Participants take one pregabalin capsule and one placebo tablet BID	318	2	318	247	318
EG002	DS-5565 QD	Participants take one each of placebo tablet and capsule in the morning and one DS-5565 tablet once daily (QD) with a placebo capsule in the evening	320	5	320	229	320
EG003	DS-5565 BID	Participants take one DS-5565 tablet and one placebo capsule BID	320	8	320	251	320