A 52-week study of gabapentin enacarbil in restless legs syndrome.
OBJECTIVE
This open-label, multicenter, 52-week extension study (NCT00333359) assessed the long-term safety and efficacy of gabapentin enacarbil in subjects with moderate-to-severe primary restless legs syndrome (RLS).


METHODS
Subjects had completed one of 4 randomized, double-blind parent studies (XP052/XP053/XP081/XP083). Gabapentin enacarbil 1200 mg was administered once daily at 5 pm; dose adjustments to 600 or 1800 mg were permitted based on investigator judgment. Safety assessments included adverse events (AEs), vital signs, clinical laboratory tests, and electrocardiograms. Efficacy evaluations included the International Restless Legs Scale total score and the investigator-rated Clinical Global Impression-Improvement scale, at week 52 last observation carried forward.


RESULTS
The safety population comprised 573 subjects; 386 (67.4%) completed the study. Treatment-emergent AEs were reported by 80.1% of subjects and led to withdrawal in 10.3% of subjects; most (67.7%) were mild or moderate in intensity. The most common AEs were somnolence and dizziness (19.7% and 11.5% of subjects). Twenty subjects (3.5%) reported serious AEs; one subject died (fall, 25 days after stopping gabapentin enacarbil, judged not treatment related). No serious AE occurred in more than 1 subject. No clinically relevant changes were reported in vital signs, laboratory parameters, or electrocardiograms. At week 52 last observation carried forward, the mean (SD) change from parent study baseline in International Restless Legs Scale total score was -15.2 (8.85 [parent study baseline score, 23.2 (5.03)]), and 84.8% of subjects were Clinical Global Impression-Improvement responders ("much improved" or "very much improved").


CONCLUSIONS
Gabapentin enacarbil was generally safe and well tolerated and improved RLS symptoms in subjects with moderate-to-severe primary RLS for up to 64 weeks of treatment.
Quest Research Institute, Farmington Hills, MI 48334, USA. aellenbogen@comcast.net
Aaron L
AL
Ellenbogen
Stephen G
SG
Thein
David H
DH
Winslow
Philip M
PM
Becker
Jerry M
JM
Tolson
Marie-Liesse
ML
Lassauzet
Dan
D
Chen
D000328:Adult; D000368:Aged; D002219:Carbamates / Q000009:adverse effects* / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D018682:GABA Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012148:Restless Legs Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
C493250:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; D002219:Carbamates; D018682:GABA Agents; D005680:gamma-Aminobutyric Acid