Treatment of Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
Condition: Diabetic Peripheral Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies
Intervention: DS-5565 tablet; pregabalin capsule; Placebo tablet; placebo capsule
Intervention description: 5mg and 10mg tablets; 75mg and 150mg over-encapsulated
Intervention MeSH terms: Pregabalin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 452.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Keywords: pain, diabetes, neuropathy

Summary:

      The purpose of this study is to evaluate the safety, tolerability and effectiveness of
      DS-5565 compared to placebo (inactive substance) and pregabalin in diabetic subjects with
      DPN.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age > 18 years of age

          2. Able to give informed consent and willing to comply with scheduled visits, treatment
             plan, laboratory tests, and other trial procedures

          3. Type 1 or type 2 diabetes with a hemoglobin A1c (HbA1c) ≤ 10% at Screening and on a
             stable antidiabetic medication regimen for at least 30 days prior to Screening
             (insulin therapy is acceptable)

          4. Painful distal symmetrical sensorimotor polyneuropathy (as per American Society of
             Pain Educators guidelines ) diagnosed for at least 6 months, based on neurological
             history and/or examination; diagnosis includes absent or reduced deep tendon reflexes
             at both ankles

          5. At Screening, a pain score of ≥ 40 mm on the SF-MPQ VAS

          6. At Randomization, a pain score of ≥ 40 mm on the SF-MPQ VAS and an ADPS of ≥ 4 on the
             11-point NRS, the latter calculated from a minimum of 4 pain ratings in daily diaries
             obtained during the 1-week Baseline Period (prior to randomization)

          7. Creatinine clearance > 60 mL/min (estimated using the Cockcroft-Gault equation)

          8. Antidiabetic and other medications anticipated to remain stable and constant during
             the study period

          9. Women of child bearing potential (WOCBP) must be using an adequate method of
             contraception as detailed in the protocol to avoid pregnancy during the study and for
             4 weeks after study completion

        Exclusion Criteria:

          1. Diagnosis of mononeuropathy

          2. Use of concomitant medications that may confound assessments of efficacy and/or safety
             (see Section 5.2)

          3. Major psychiatric disorders

          4. Have had a malignancy other than basal cell carcinoma within the past 2 years

          5. At Visit 1, have a white blood cell count < 2500/mm3, neutrophil count < 1500/mm3, or
             platelet count < 100 x 103/mm3

          6. Clinically significant unstable diabetes mellitus, unstable hepatic, respiratory, or
             hematologic illness, unstable cardiovascular disease (including myocardial infarction
             in the 3 months prior to Visit 1), or symptomatic peripheral vascular disease

          7. Clinically significant findings on the Screening ECG

          8. History of pernicious anemia, untreated hypothyroidism, chronic hepatitis B, hepatitis
             B within the past 3 months, or human immunodeficiency virus infection

          9. Amputations of body parts other than toes

         10. Prior therapeutic failure of pregabalin or gabapentin (considered unresponsive or
             intolerant to treatment); therapeutic failure implies lack of efficacy following full
             titration to effective doses (eg, 300 mg/day for pregabalin)

         11. Known hypersensitivity to pregabalin or gabapentin

         12. Requirement for concomitant anticonvulsant and antidepressant therapy, with the
             exception of stable doses of SSRIs

         13. Neurologic disorders unrelated to DPN that may confound the assessment of pain
             associated with DPN

         14. Skin conditions that could alter sensation

         15. Other sources of pain that may confound assessment or self-evaluation of the pain due
             to DPN

         16. Abuse of prescription medications, street drugs or alcohol (including alcohol
             dependence) within the last 1 year

         17. Current enrollment in another investigational study, participation in another
             investigational study with the past 30 days, or other current or recent use of any
             investigational drug

         18. Pregnancy (as based on lab test results) or breast feeding

         19. Laboratory values exceeding limits listed in Table 4.1 of the protocol