Original Research Article
A Phase 2a, Randomized, Crossover Trial of Gabapentin Enacarbil for the Treatment of Postherpetic Neuralgia in Gabapentin Inadequate Responders
- Conflict of Interest Statement: This study was sponsored by GlaxoSmithKline. Drs Chen, Graff, and Schwartzbach, and Mr Bell, Ms Berges, Ms Harding, Ms Kavanagh, Ms Warren, and Ms McClung are all employees of and stakeholders in GlaxoSmithKline. Ms Hunter was an employee of GlaxoSmithKline at the time of this study. Dr Zhang was an investigator in the conduct of this study and received funding from GlaxoSmithKline. Dr Rainka was a subinvestigator of Dr Zhang in the conduct of this study. Drs Harden and Freeman were paid consultants for GlaxoSmithKline and provided input into the study design and/or interpretation of the data. Additionally, Dr Harden has research grants from Forest, Covidien, Depomed, DOD, and Mayday Fund, and has participated in advisory boards with Nevro, Astellas, Depomed, and Covidien.
- Funding Statement: This study was sponsored by GlaxoSmithKline.
- Authors' Contributions: RNH participated in the design and planning of the study, and in preparation of the manuscript. RF participated in the design and planning of the study and in critical review of the manuscript. MR and LZ participated in the conduct of the study and in critical review of the manuscript. CB, AB, CC, and CM participated in the design, setup, review of the clinical data and interpretation of the study, and in the preparation of this manuscript. OG participated in the review of the clinical data and interpretation of the study, and in the preparation of this manuscript. KH and SW participated in the setup of the study and data collection, and in the preparation of the manuscript. SH participated in the review of the clinical data and interpretation of the study, and in the preparation of the manuscript. CS participated in the setup of the study, data collection, review of the clinical data and interpretation of the study, and in the preparation of this manuscript. SK participated in the interpretation of the study data and results, and in the preparation of this manuscript.
- Previous publication: This work has not been published previously, in any form.
To compare the efficacy of high-dose (3,600 mg/day) vs low-dose (1,200 mg/day) oral gabapentin enacarbil (GEn) on pain intensity in adults with postherpetic neuralgia (PHN) and a history of inadequate response to ≥1,800 mg/day gabapentin.
Multicenter, randomized, double-blind, crossover study (NCT00617461).
Thirty-five outpatient centers in Germany and the United States.
Subjects aged ≥18 years with a diagnosis of PHN.
During a 2-week baseline period, subjects received open-label treatment with 1,800 mg/day gabapentin. Subjects who had a mean 24-hour average pain intensity score ≥4 during the last 7 days of the baseline period were randomized to receive GEn (1,200 or 3,600 mg/day) for treatment period 1 (28 days), followed by GEn 2,400 mg/day (4 days), and the alternate GEn dose for treatment period 2 (28 days).
There was a modest but significant improvement in pain intensity scores with GEn 3,600 mg vs 1,200 mg (adjusted mean [90% confidence interval] treatment difference, −0.29 [−0.48 to −0.10]; P = 0.013). The difference in efficacy between doses was observed primarily in subjects who received the higher dose during treatment period 2; certain aspects of the study design may have contributed to this outcome. Plasma steady-state gabapentin exposure during GEn treatment was as expected and consistent between treatment periods. No new safety signals or adverse event trends relating to GEn exposure were identified.
While the overall results demonstrated efficacy in a PHN population, the differences between treatment periods confound the interpretation. These findings could provide insight into future trial designs.