Gabapentin extended-release tablets for the treatment of patients with postherpetic neuralgia: a randomized, double-blind, placebo-controlled, multicentre study.Clin Drug Investig. 2010; 30(11):765-76.CD
Postherpetic neuralgia (PHN) is a neuropathic pain syndrome that may develop subsequent to healing of herpes zoster rash.
This study aimed to determine the efficacy and safety of gabapentin extended-release (gabapentin ER) tablets for the treatment of patients with PHN and to determine whether optimal benefits might be achieved with once-daily (QD) or divided-dose (DD) administration.
This was a 10-week, randomized, double-blind, placebo-controlled, multicentre trial comparing gabapentin ER (total daily dose 1800 mg) either QD or as an asymmetrical DD with placebo in 407 patients with post-zoster pain for >or=3 months and a baseline average daily pain score (ADP)>or=4 on a 0-10 Likert numerical rating scale. The primary efficacy outcome was the ADP score mean change from baseline to week 10 using baseline observation carried forward (BOCF). Secondary efficacy outcomes included changes to week 10 in last observation carried forward (LOCF) ADP score, LOCF average daily sleep interference score, Short-Form McGill Pain Questionnaire score, Neuropathic Pain Scale score, and Brief Pain Inventory score.
Of 407 randomized patients, 400 were included in the intent-to-treat population (gabapentin ER QD, n=134; gabapentin ER DD, n=135; placebo, n=131). Between-group differences in the least squares (LS) mean changes in BOCF ADP scores did not reach statistical significance (gabapentin ER QD -1.85 [p=0.110 vs placebo]; gabapentin ER DD -1.72 [p=0.255 vs placebo]; placebo -1.42). In the LOCF analysis, the LS mean ADP score for the gabapentin ER QD group, but not for the DD group, improved compared with placebo (gabapentin ER QD, -2.28; p=0.032 vs placebo). Improvements compared with placebo were also observed in the gabapentin ER QD group, but not for the DD group, for mean daily sleep interference scores (gabapentin ER QD, -2.49; placebo, -1.63; p<0.001). Most adverse events (AEs) were mild or moderate. Among gabapentin-treated patients, 12% and 11% withdrew due to AEs, most commonly for dizziness (2% and 3%), in the gabapentin ER QD and DD groups, respectively. Treatment-related AEs in the gabapentin ER-treated groups occurred in 31% of patients. The most common AEs in the gabapentin ER QD and DD groups included dizziness (10% and 15%), headache (4% and 7%), somnolence (3% and 7%) and peripheral oedema (5% and 5%), respectively.
The primary efficacy endpoint for this study of gabapentin ER was not met, most likely due to the unexpectedly large placebo response. Outcomes on secondary endpoints suggest the potential efficacy of gabapentin ER QD. Gabapentin ER was well tolerated in this study. [Clinicaltrials.gov identifier NCT00335933].