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Pregabalin as Treatment of Painful Diabetic Peripheral Neuropathy (DPN): Nerve Conduction and Analgesic Effect in a 13-week Double-Blind, Placebo-Controlled Trial
J. Rosenstock1, J. Arezzo2, L. Pauer3, L. LaMoreaux3, J. Barrett, PhD4, and E. Durso-De Cruz4. (1) Dallas Diabetes & Endo Research Center,, 7777 Forest Lane, C618, Dallas, TX 75230, (2) Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, (3) Pfizer Global R&D, 2800 Plymouth Rd., Ann Arbor, MI 48105, (4) Pfizer Global Pharmaceuticals, 235 E 42nd St, New York, NY 10017
To further elucidate the safety and efficacy of pregabalin at the upper end of its dosing range, this 13-week trial evaluated nerve conduction and the analgesic effect of pregabalin 600 mg/d (BID) in patients with painful DPN. Amplitude and conduction velocity were primary endpoints and were assessed at baseline, endpoint, and 2-week follow-up for 4 nerves: median-motor, median-sensory, ulnar-sensory, and peroneal-motor. The study's primary efficacy measure was endpoint mean pain score (MPS) on an 11-point numeric rating scale (NRS) derived from patients' daily pain diaries. Secondary efficacy measures included weekly MPS and analysis of endpoint and weekly sleep-interference scores (also on an 11-point NRS). 82 patients were randomized to double-blind treatment with pregabalin, 85 to placebo. After a 1-week dosage escalation, pregabalin patients received 600 mg/d for 12 weeks. No statistically significant differences were observed for any of the 4 nerves based on predefined criteria. Pregabalin patients' MPS was significantly lower than placebo patients' at endpoint (mean difference, ¨C1.28; P<.001). Significant pain improvement among pregabalin patients was evident at Week 1 and was sustained at every weekly timepoint. Analysis of sleep-interference scores showed pregabalin was statistically significantly superior to placebo at every weekly timepoint (except Weeks 9 and 10) and at endpoint. In the open-label extension, patients received 150-600 mg/d pregabalin (BID), adjusted to optimize efficacy and tolerability, for as long as 6 months. During open-label treatment, 97% of patients received pregabalin at dosages °Ý300 mg/d. Pregabalin was generally well tolerated, with 80/104 patients completing 6-months of treatment. 15 patients (14%) withdrew because of AEs. Peripheral edema, dizziness, and somnolence were the most common AEs. BID dosing at the upper end of pregabalin's effective dosing range showed robust and sustained efficacy and was well tolerated, with no meaningful effect on nerve conduction during 13 weeks of double-blind treatment.