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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pain Associated With Fibromyalgia

Intervention / Treatment
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* Drug: DS-5565


Participation Criteria
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Eligibility Criteria
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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 13) 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DS-5565<br>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<br>* DS-5565 15 mg tablet for oral administration<br>* Other names: Investigational product;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Week 52 postdose | 
| Hospital Anxiety Depression Scale (HADS) Depression and Anxiety Scores for DS-5565 | 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. | Day 0 (baseline) up to Week 52 postdose | 
| EuroQol Five Dimensions Questionnaire (EQ-5D) Measure for DS-5565 | 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. | Day 0 (baseline) up to Week 52 postdose | 
| Short Form-36 (SF-36) Measure for DS-5565 | 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. | Day 0 (baseline) to Week 52 postdose | 
| Pain-Associated Sleep Interference as Assessed by Average Daily Sleep Interference Score (ADSIS) for DS-5565 | 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. | Day 0 (baseline) up to Week 52 postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, fibromyalgia