Safety and efficacy of pregabalin in adolescents with fibromyalgia: a randomized, double-blind, placebo-controlled trial and a 6-month open-label extension study

Abstract

Background: Fibromyalgia (FM) is a common pain condition characterized by widespread musculoskeletal pain and tenderness. Pregabalin is an approved treatment for adults in the United States, but there are no approved treatments for adolescents with FM.

Methods: This was a 15-week, randomized, double-blind, placebo-controlled study and 6-month open-label safety trial of flexible-dose pregabalin (75-450 mg/day) for the treatment of adolescents (12-17 years) with FM. Primary outcome was change in mean pain score at endpoint (scored from 0-10, with 24-h recall). Secondary outcomes included global assessments and measures of pain, sleep, and FM impact.

Results: A total of 107 subjects were randomized to treatment (54 pregabalin, 53 placebo) and 80 completed the study (44 pregabalin, 36 placebo). Improvement in mean pain score at endpoint with pregabalin versus placebo was not statistically significant, treatment difference (95 % CI), -0.66 (-1.51, 0.18), P = 0.121. There were significant improvements with pregabalin versus placebo in secondary outcomes of change in pain score by week (P < 0.05 for 10 of 15 weeks); change in pain score at week 15 (1-week recall), treatment difference (95 % CI), -0.87 (-1.68, -0.05), P = 0.037; and patient global impression of change, 53.1 % versus 29.5 % very much or much improved (P = 0.013). Trends toward improvement with pregabalin in other secondary outcomes measuring pain, sleep, and FM impact were not significant. Safety was consistent with the known profile of pregabalin in adults with FM.

Conclusion: Pregabalin did not significantly improve the mean pain score in adolescents with FM. There were significant improvements in secondary outcomes measuring pain and impression of change.

Trial registrations: NCT01020474 ; NCT01020526 .

Keywords: Clinical trial; Juvenile fibromyalgia; Pain; Pregabalin.

Fig. 1

Subject disposition. AE adverse event, FAS full analysis set, PPAS per protocol analysis set

Fig. 2

Primary efficacy outcome and sensitivity analyses in the double-blind trial BOCF baseline observation carried forward, CI confidence interval, FAS full analysis set; LOCF last observation carried forward, mBOCF modified baseline observation carried forward (applying BOCF rule for subjects discontinued due to adverse events and LOCF rule for subjects discontinued due to any other reason); SE standard error. For the primary outcome the FAS was assessed, where missing data for week 15 mean pain score were imputed based on distribution of baseline pain scores if patients discontinued due to adverse events or abnormal laboratory test results or lack of efficacy; otherwise, if subjects discontinued due to other reasons, it was imputed based on distribution of post-baseline weekly mean pain scores using Markov chain Monte Carlo method. Mean (SD) pain score at baseline was 6.94 (1.23) with pregabalin and 6.95 (1.27) with placebo

Fig. 3

Mean pain score by week in the double-blind trial. *P < 0.05 for pregabalin compared with placebo at each week

Fig. 4

Patient global impression of change and parent global impression of change in the double-blind trial. Responders were those who were very much improved or much improved at endpoint. P values for pregabalin compared with placebo for each assessment. GIC Global impression of change