An Open-Label, Randomized Comparison of Duloxetine, Pregabalin, and the Combination of Duloxetine and Gabapentin among Patients with Inadequate Response to Gabapentin for the Management of Diabetic Peripheral Neuropathic Pain
Abstract Number: 969-P
Authors: ROBERT J. TANENBERG, GORDON IRVING, RICHARD C. RISSER, JONNA AHL, SANDRA MALCOLM
Institutions: Greenville, NC, Seattle, WA, Indianapolis, IN
Results: The aim of this investigation was to test the non-inferiority of duloxetine monotherapy compared to pregabalin monotherapy among patients with diabetic peripheral neuropathic pain (DPNP). This was a 12-week, phase IV, open-label, randomized, multi-center parallel study in patients with DPNP, who had been treated with a stable dose of gabapentin (at least 900 mg/d) and had an inadequate response (defined by having a daily pain score ≥4 on an 11-point likert scale). Patients were randomly assigned to duloxetine (D) monotherapy (N=138), pregabalin (P) monotherapy (N=134), or a combination of duloxetine and gabapentin (D+G) (N=135). The primary efficacy variable was improvement in weekly mean 24-hour average pain at 12 weeks (based on a 0-to-10 likert scale). The primary objective was a non-inferiority comparison on the intent-to-treat population between P and D on this primary efficacy measure. Non-inferiority to P would be declared if the mean improvement for D was no worse than mean improvement for P within the statistical variability of 0.8 units. Estimated mean improvement (decrease in pain score) at 12 weeks was 2.12 for P and 2.62 for D, representing an observed +0.49 advantage for D. The 97.5% lower confidence bound was -0.05, establishing non-inferiority. The estimated mean improvement for D+G was 2.39, the 97.5% lower confidence bound was -0.32, also establishing non-inferiority. Completion rates did not differ significantly between the groups (D, 63%; P, 71.6%; D+G, 73.3%). Discontinuation due to adverse events (AEs) was significantly greater in D vs. P patients (19.6% vs.10.4%; p=.042); D+G (13.3%) vs. P or D was not significant (p=.573; p=.193, respectively). AEs that occurred significantly more frequently between groups were: D>P: nausea, insomnia, hyperhydrosis, decreased appetite; D>D+G: insomnia; P>D: peripheral edema; D+G>P: nausea, hyperhydrosis, decreased appetite, and vomiting. In conclusion, duloxetine met statistical criteria for non-inferiority compared with pregabalin for the treatment of pain in patients with DPNP.