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

Diabetes Care. 2014 Dec;37(12):3253-61. doi: 10.2337/dc14-1044. Epub 2014 Sep 17.

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).

Research design and 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Analgesics / administration & dosage*
  • Analgesics / adverse effects
  • Bridged Bicyclo Compounds / administration & dosage*
  • Bridged Bicyclo Compounds / adverse effects
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Neuropathies / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuralgia / drug therapy*
  • Placebos
  • Pregabalin
  • Treatment Outcome
  • gamma-Aminobutyric Acid / analogs & derivatives
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • Analgesics
  • Bridged Bicyclo Compounds
  • Placebos
  • Pregabalin
  • gamma-Aminobutyric Acid
  • mirogabalin