title: Efficacy and safety of mirogabalin (DS-5565) for the treatment of diabetic peripheral neuropathic pain: a randomized, double-blind, placebo- and active comparator-controlled, adaptive proof-of-concept phase 2 study.
abstract: OBJECTIVE
  We aimed to identify doses of mirogabalin (DS-5565) providing clinically meaningful efficacy with manageable side effects for treatment of diabetic peripheral neuropathic pain (DPNP).
  
  
  METHODS
  Adults (≥18 years) with type 1 or 2 diabetes, HbA₁c ≤10% at screening, and DPNP for ≥6 months were eligible for study participation. Subjects (n = 452) were randomized (2:1:1:1:1:1:1 ratio) to placebo, dose-ranging mirogabalin (5, 10, 15, 20, and 30 mg/day), or pregabalin (300 mg/day) for 5 weeks. The primary end point was weekly change in average daily pain score (ADPS; 0 to 10 numeric rating scale) from baseline to week 5 (minimally meaningful effect, ≥1.0-point decrease versus placebo). ANCOVA was conducted using last observation carried forward, and treatment effect least squares (LS) means were provided for each contrast. Safety assessments included adverse events (AEs), clinical laboratory tests, and electrocardiograms.
  
  
  RESULTS
  LS mean differences in change in ADPS from baseline to week 5 versus placebo were -0.22, -0.53, -0.94, -0.88, and -1.01 for the mirogabalin 5-, 10-, 15-, 20-, and 30-mg/day treatment groups, respectively, and -0.05 in the pregabalin group (P < 0.05 versus placebo for mirogabalin 15, 20, and 30 mg/day). Most frequent AEs (n = 277) were primarily mild to moderate dizziness (9.4%), somnolence (6.1%), and headache (6.1%); otherwise, mirogabalin was well tolerated.
  
  
  CONCLUSIONS
  Mirogabalin 15, 20, and 30 mg/day had statistically significant reductions in ADPS versus placebo, and mirogabalin 30 mg/day also met the criteria of minimally meaningful effect. Mirogabalin may be a promising new treatment option for patients with DPNP.
authors.affiliation: Eastern Virginia Medical School, Norfolk, VA vinikai@evms.edu.
authors.forename: Aaron
authors.initials: A
authors.lastname: Vinik
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: MMS Holdings Inc., Canton, MI.
authors.forename: Uma
authors.initials: U
authors.lastname: Sharma
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: Karen
authors.initials: K
authors.lastname: Feins
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: Ching
authors.initials: C
authors.lastname: Hsu
authors.affiliation: Daiichi Sankyo Development, Gerrards Cross, Buckinghamshire, U.K.
authors.forename: Domenico
authors.initials: D
authors.lastname: Merante
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D010919:Placebos; D000069583:Pregabalin; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D001643:Bridged Bicyclo Compounds; D010919:Placebos; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; C000598618:mirogabalin