An Open-Label Extension Study of DS-5565 for 52 Weeks in Pain Associated With Fibromyalgia
Condition: Pain Associated With Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Intervention: DS-5565
Intervention description: DS-5565 15 mg tablet for oral administration
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2485.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pain; fibromyalgia

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.
    

Eligibility criteria:

        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)