Treatment of Pain Associated With Fibromyalgia
Condition: Pain Associated With Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Intervention: DS-5565; Pregabalin; Placebo tablet; Placebo capsule
Intervention description: DS-5565 15 mg QD or BID; tablet for oral use; Pregabalin capsule for oral use; 75 mg capsule for one week, then 150 mg capsule; Placebo tablet for oral use, matching DS-5565 tablet; Placebo capsule for oral use, matching pregabalin capsule
Intervention MeSH terms: Pregabalin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1301.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pain; fibromyalgia

Summary:

      The main objective of this trial is to compare change in weekly average daily pain score
      (ADPS) from baseline to Week 13 in participants receiving either dose of DS-5565 versus
      placebo.

      Weekly ADPS is based on daily pain scores reported by the subject that best describes his or
      her worst pain over the previous 24 hours.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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
             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 C-SSRS questions at screening must be
             excluded. 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

          -  Subjects 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.

          -  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

          -  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

          -  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.

          -  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.

          -  Subjects 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 subjects documented to have Gilbert's syndrome may be
             enrolled.