Study of the Safety, Tolerability and Efficacy of V3381 in Patients With Diabetic Peripheral Neuropathic Pain
Condition: Diabetic Peripheral Neuropathic Pain
MeSH terms: Neuralgia; Diabetic Neuropathies
Study type: Interventional
Phase: Phase 2

Summary: 
      Randomised, double-blind, placebo-controlled, parallel group, multicentre study of oral doses
      of V3381, titrated to effect. A 2-week single-blind run-in period will be followed by a 13
      week double-blind titration and maintenance phase. Doses will be titrated up in 100 mg bid
      increments every one or two weeks, starting from 100 mg bid. A 2 week follow-up period will
      conclude patient participation in the study.
    

Detailed description: 
      Patients who provide written informed consent will be screened for entry into the study.

      Patients will initially enter a 2-week single-blind run-in phase, during which they will
      complete an 11 point numerical pain rating scale (NPRS) on their average daily pain; patients
      with a mean weekly score of >4 and <9 will be allowed to continue in the study to
      randomisation (unless they have exhibited a >50% decrease in pain score, compared to the Day
      -14 score, during the run-in).

      Patients will be randomised to receive either Placebo (PL) bid (n=75) or V3381 (n=75) and
      will initially be treated with 100 mg V3381 (or placebo equivalent) twice daily (bid) for one
      week. Patients will remain on the same study treatment throughout the trial. At the end of
      one week those patients who adequately tolerated study medication will escalate the dose of
      V3381 to 200 mg bid on a blinded basis. Patients who do not tolerate 100 mg bid will be
      withdrawn.

      After one week of treatment at the 200 mg bid dose level, those subjects who continue to
      tolerate adequately 200 mg bid study drug will escalate to 300 mg bid. Subjects who have not
      tolerated the 200 mg bid dose may revert to the 100 mg bid dose and should remain at this
      dose level for the remainder of the trial.

      After a further 2 weeks of treatment those subjects who continue to tolerate adequately 300
      mg bid study drug will escalate to 400 mg bid. Subjects who have not tolerated the 300 mg bid
      dose may revert to the 200 mg bid dose and should remain at this dose level for the remainder
      of the trial.

      Subjects will then remain on these doses (that is, the dose of V3381 or placebo which they
      tolerate) for the remaining 9 weeks of the treatment period. In exceptional cases of new
      intolerability developing, patients may be down-titrated to the next lower dose level.

      All patients will be provided with the rescue medication paracetamol (acetaminophen) 650 mg
      up to four times daily (North America [NA]) or 1000 mg up to three times daily (Europe [EU])
      to supplement study drug, should they wish to do so, throughout the study, including the
      single-blind placebo phase.

      Patients will be expected to attend the clinic 9 times (at Screening, Baseline, Week 1, Week
      2, Week 4, Week 7, Week 10, Week 13 and Follow-up clinic visits) for safety and efficacy
      assessments. The safety assessments will include biochemistry, haematology and urinalysis
      tests, 12 lead electrocardiogram (ECG), vital signs, recording of adverse events, Beck
      Depression Inventory, review of medication compliance, and of blood glucose control.

      The following assessments will also be conducted at each clinic visit during treatment and
      follow up:

        -  Modified Brief Pain Inventory for diabetic painful neuropathy (DPN)

        -  Neuropathic Pain Symptom Inventory

        -  Patient Clinical Global Impression score

        -  Investigator Clinical Global Impression score

      The Medical Outcomes Survey Short Form-36, Version 2 will be assessed at baseline and Visit
      8.

      Subjects will complete home diaries on a daily basis on which they will rate average pain
      using the 11-point Likert NPRS. Sleep interference scores, worst daily pain and use of rescue
      medication will also be recorded on the daily diaries.

      A Steering Committee will be established to provide oversight of the conduct of the trial. A
      Data Safety Monitoring Board (DSMB) will be convened to periodically review patient safety.
    

Intervention name(s): V3381; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 100 mg capsules, titrated to a maximum of 400 mg bid for 13 weeks; Capsule, bid, for 13 weeks
Other intervention name(s): Indantadol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Safety; Tolerability; Efficacy; Patients; Diabetic peripheral neuropathic pain.