Safety Study of DS-5565 for Treatment of Fibromyalgia Pain in Subjects With Chronic Kidney Disease

This is an interventional treatment trial for Fibromyalgia focused on measuring chronic kidney disease, . α2δ ligands, mirogabalin, pain relief, kidney metabolism Read More

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