Abstract| Volume 14, ISSUE 4, SUPPLEMENT , S68, April 2013

Efficacy and safety of subcutaneous tanezumab in patients with pain related to diabetic peripheral neuropathy (NCT01087203)

      This randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluated efficacy, safety, and tolerability of tanezumab in patients with diabetic peripheral neuropathy (DPN) pain. Patients received two subcutaneous injections of placebo or tanezumab (20 mg) at 8-week intervals. Efficacy was evaluated by change from baseline in average DPN pain and Patient’s Global Assessment (PGA) of DPN. Safety evaluations included adverse event reports, physical and neurological examinations, and laboratory tests. Protein gene product (PGP) 9.5-positive intraepidermal nerve fiber (IENF) density was assessed from skin biopsy sites in the thigh and distal leg. Quantitative Sensory Testing including heat-as-pain thresholds and stimulus response slopes at the thigh and foot were also performed. The study was terminated early with only 46% of planned enrollment (tanezumab n=38; placebo: n=35) and most patients receiving a single dose of study medication due to a partial clinical hold placed on most tanezumab clinical studies by the FDA. At Week 8, tanezumab treatment resulted in significantly greater mean pain reduction (least squares mean difference versus placebo: -1.32; p=0.009), but no significant improvement or worsening in PGA of DPN (p>0.05). The most frequently reported adverse events with tanezumab treatment were arthralgia, pain in extremity, back pain, and myalgia. More tanezumab-treated patients reported adverse events of abnormal peripheral sensation. Nearly all patients (97%) treated with tanezumab had final neurological examinations that were either unchanged from their baseline assessment or exhibited small, clinically insignificant changes. A small decline in IENF density was evident with tanezumab at both locations while a small increase in IENF density occurred with placebo treatment; changes in IENF were not statistically significant. For the heat-as-pain evaluation, no significant thermal hyperalgesia was demonstrated. In this initial study for DPN-related pain, tanezumab was generally safe and efficacious with significantly improved pain relief versus placebo treatment. Supported by Pfizer Inc.