Safety Study of DS-5565 for Treatment of Fibromyalgia Pain in Subjects With Chronic Kidney Disease
Condition: Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes; Kidney Diseases; Renal Insufficiency, Chronic
Intervention: DS-5565; Placebo
Intervention description: DS-5565 7.5 mg tablet for oral use; Placebo tablet for oral use to match DS-5565 7.5 mg tablet
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: chronic kidney disease; . α2δ ligands; mirogabalin; pain relief; kidney metabolism

Summary:

      DS-5565 (mirogabalin) is being studied as treatment for fibromyalgia (FM) pain. Because it is
      excreted through the kidneys, people who have reduced kidney function will not process the
      drug as well as with those with normal kidney function, so the dose must be reduced. This
      study will test two reduced dose levels for both moderately reduced and severely reduced
      kidney function. The study will test the hypothesis that the drug will be safe and
      well-tolerated in people who have both fibromyalgia and chronic kidney disease.
    

Eligibility criteria:

        Abbreviations: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine
        clearance [(CrCL) determined by the central laboratory using the Cockcroft-Gault equation],
        upper limit of normal (ULN), Columbia-Suicide Severity Rating Scale (C-SSRS)

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Able to give written informed consent

          -  Able to complete patient-reported questionnaires per the Investigator's judgment

          -  Estimated CrCl between 15-59 mL/min from serum creatinine by the central laboratory
             using the Cockcroft-Gault equation

          -  Fibromyalgia meeting American College of Rheumatology criteria for FM:

               -  Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5 or WPI
                  3 to 6 and SS scale score ≥ 9,

               -  Pain in at least 11 of 18 specific tender point sites,

               -  Symptoms have been present at a similar level for at least 3 months, and

               -  The subject does not have a disorder that would otherwise explain the pain

          -  Average Daily Pain Score of ≥ 4 on the 11-point numeric rating scale (NRS) over the 7
             days prior to randomization (based on completion of at least 4 daily pain assessments
             during the 7-day baseline period prior to randomization)

          -  Women of child bearing potential (WOCBP) must be using adequate methods of
             contraception to avoid pregnancy during the study and for 4 weeks after study
             completion.

        Exclusion Criteria:

          -  Need for ongoing use of concomitant chronic pain medications or any new
             non-pharmacological pain management techniques that may confound assessments of
             efficacy and/or safety, including neurolytic treatments (destruction of nerves by
             chemicals, heat, cold) or surgery, intrathecal pumps, spinal cord stimulators or
             psychological support within the previous year. Also excluded: topical capsaicin
             within 6 months; or systemic corticosteroids within 3 months of baseline period.

          -  Unable to undergo pre-study washout of prohibited concomitant medications

          -  Subjects with recent history (i.e., within 1 year prior to screening) of alcohol abuse
             or illicit drug use (cocaine, heroin, marijuana [including medical, prescribed], etc.)

          -  Use of any selective serotonin reuptake inhibitor (SSRI), unless the subject has been
             on a stable dose for ≥ 90 days prior to screening and is not anticipated to need any
             dose adjustment during the course of the study

          -  Subjects with severe or uncontrolled depression that, in the judgment of the
             Investigator, makes the subject inappropriate for entry into the study

          -  Significant neurological or psychiatric disorder unrelated to neuropathic pain

          -  Other severe pain (eg, sciatica, rheumatoid arthritis) that might impair the
             assessment of neuropathic pain

          -  CrCl ≥ 60 mL/min estimated from serum creatinine by the central laboratory using the
             Cockcroft-Gault equation.

          -  Subjects who are on hemodialysis or who require hemodialysis before the follow-up
             assessment; acute renal failure; history of kidney transplant

          -  Any history of a malignancy other than basal cell carcinoma within the past 5 years

          -  Clinically significant unstable neurologic, ophthalmologic, hepatobiliary,
             respiratory, or hematologic illness or unstable cardiovascular disease (eg, severe
             hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) within 12
             months prior to screening

          -  Pregnancy or breast feeding or intent to become pregnant during the study period

          -  Known hypersensitivity to 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.

          -  Clinically significant ECG abnormalities at the Screening Visit

          -  Subjects who are at risk of suicide, as defined by their responses to the C-SSRS or in
             the opinion of the Investigator. Note: Subjects answering "yes" to any of the
             questions about active suicidal ideation/intent/behaviors that occurred 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
             subjects should be referred immediately to a mental health professional for
             appropriate evaluation.

          -  Subjects who are unlikely to comply with the protocol (eg, uncooperative attitude,
             inability to return for subsequent visits, and/or otherwise considered by the
             Investigator to be unlikely to complete the study)

          -  Subject is currently enrolled in, or it has been fewer than 30 days since ending,
             another investigational device or drug study or is receiving another investigational
             agent.

          -  Subjects who are employees or immediate family of employees of the study site,
             Sponsor, or contract research organization (CRO)

          -  Screening laboratory values outside the limits listed in the table below:

               -  Hematology

               -  Hemoglobin < 8 g/dL

               -  Platelet count < 100,000/mm3

               -  Absolute neutrophil count < 1,500/mm3

               -  Blood chemistry

               -  AST > 2.0 × ULN

               -  ALT > 2.0 × ULN

               -  Alkaline phosphatase > 1.5 × ULN

               -  Total bilirubin > 1.2 × ULN (If a subject has total bilirubin >ULN: unconjugated
                  and conjugated bilirubin fractions should be analyzed and only subject documented
                  to have Gilbert's syndrome may be enrolled)

               -  Creatine kinase > 3.0 × ULN

               -  Calculated CrCl ≥ 60 mL/min