SLEEP 2011 Abstract Supplement

B. Clinical Sleep Science V. Sleep Disorders – Movement Disorders
Methods: Data from two 12-week, multicenter, double-blind, randomized,
placebo-controlled studies (XP052 and XP053) of subjects
with moderate-to-severe primary RLS were retrospectively pooled for
analyses of novel sleep endpoints (comparing GEn 1200mg and placebo
groups). Subjects were divided into subgroups based on response
to item 4 on the International Restless Legs Scale at baseline: severe/
very severe or moderate-to-no sleep disturbance. Two novel sleep endpoints
were derived using the sponsor-developed 24-Hour Patient RLS
Record: sleep time (ST) and time awake during the night (TAN); these
endpoints were compared with similar endpoints derived using the Pittsburgh
Sleep Diary (PghSD): total sleep time (TST) and wake time after
sleep onset (WASO).
Results: The integrated, modified intent-to-treat population comprised
427 subjects (GEn 1200mg=223; placebo=204). At baseline, 43.8%
and 56.2% of subjects reported severe/very severe and moderate-to-no
sleep disturbance, respectively. In the severe/very severe sleep disturbance
subgroup, GEn 1200mg decreased TAN compared with placebo
at Week 12/early termination (ET) (unadjusted mean [SD] change from
baseline: -17.2 [175.36] minutes for placebo, -83.1 [177.11] minutes for
GEn 1200 mg; chi-squared value for adjusted mean treatment difference
[AMTD] using nonparametric analysis of covariance [ANCOVA]: 10.9;
P=0.0010); no significant treatment difference was seen for TAN in the
moderate-to-no sleep disturbance subgroup (P=0.8047), or in either subgroup
for ST at Week 12/ET. GEn 1200mg decreased WASO compared
with placebo at Week 12/ET in both subgroups (parametric ANCOVA):
severe/very severe sleep disturbance AMTD: -12.7; 95% CI: -20.35,
-5.15; P=0.0011; moderate-to-no sleep disturbance AMTD: -4.8; 95%
CI: -8.36, -1.15; P=0.0100); no significant treatment difference was seen
in either subgroup for TST at Week 12/ET.
Conclusion: Evaluation of sleep endpoints derived using the 24-Hour
Patient RLS Record and the PghSD yielded similar results.
Support (If Any): XenoPort, Inc., Santa Clara, CA and GlaxoSmith-
Kline, Research Triangle Park, NC
0591
GABAPENTIN ENACARBIL FOR RESTLESS LEGS
SYNDROME: RESULTS FROM INTEGRATED SAFETY DATA
Caivano CK 1 , Lassauzet M 2 , Kavanagh ST 1 , VanMeter SA 1
1
GlaxoSmithKline, Research Triangle Park, NC, USA, 2 XenoPort, Inc.,
Santa Clara, CA, USA
Introduction: Gabapentin enacarbil (GEn) is a non-dopaminergic treatment
under investigation for moderate-to-severe primary Restless Legs
Syndrome (RLS). Subject data were integrated to evaluate the long-term
safety of GEn in adults with RLS.
Methods: Data from the 52-week open-label extension study XP055
and relevant parent studies were integrated to provide long-term safety
information on GEn treatment in RLS. Completers of one of four
double-blind placebo-controlled parent studies (XP052, XP053, XP081
[12-week studies], or XP083 [2-week study]) had the option of participating
in XP055. This summary includes safety data from all subjects
who received GEn in a parent study and all subjects who received GEn
in XP055. GEn was dosed once daily at 5PM with food; this grouping
included 600mg, 1200mg, 1800mg, and 2400mg.
Results: A total of 777 subjects received at least one dose of GEn; mean
(SD) age was 49.3 (12.51) years and 60% were female. Roughly half
of subjects (371/777 [48%]) received GEn for ≥12 months and 74%
(577/777) received GEn for ≥3 months. Total duration of exposure was
highest in the 1200mg group (307.24 subject-years). Somnolence (30%)
and dizziness (22%) were the most frequently reported adverse events
(AEs) in GEn-treated subjects; each led to withdrawal in 2% (18/777)
of subjects. Any AE led to withdrawal of 14% (108/777) of subjects.
Serious AEs were reported by 3% (20/777); none were reported more
than once. Most subjects reported no RLS symptoms or a delay in time
to onset of symptoms based on the 24-hour RLS Symptom Diary at each
assessment (Week 12 [78% (303/390)] - Week 64/65 [87% (151/173)]).
Conclusion: The most common AEs were somnolence and dizziness;
generally these AEs were not treatment limiting. There was no pattern of
earlier RLS symptom onset observed that would suggest augmentation
associated with up to 64 weeks of GEn treatment.
Support (If Any): XenoPort, Inc., Santa Clara, CA and GlaxoSmith-
Kline, Research Triangle Park, NC
0592
AN INTEGRATED ANALYSIS OF 600MG AND 1200MG
DOSES OF GABAPENTIN ENACARBIL VERSUS PLACEBO
IN SUBJECTS WITH MODERATE-TO-SEVERE RESTLESS
LEGS SYNDROME (RLS) PARTICIPATING IN THREE 12-
WEEK TRIALS
Warren S 1 , Kavanagh ST 1 , VanMeter SA 1 , Barrett RW 2
1
Neurosciences, GlaxoSmithKline, Research Triangle Park, NC, USA,
2
XenoPort, Inc., Santa Clara, CA, USA
Introduction: Gabapentin enacarbil (GEn), an investigational nondopaminergic
treatment that provides dose-proportional, sustained
exposure to gabapentin, has demonstrated efficacy in reducing RLS
symptoms. Data from subjects with RLS who participated in three 12-
week trials were retrospectively integrated to evaluate the efficacy and
tolerability of GEn.
Methods: Data from three 12-week, multicenter, double-blind, randomized,
placebo-controlled studies were integrated for the GEn 600mg,
GEn 1200mg, and placebo groups to provide efficacy and tolerability
data on GEn treatment in RLS. Analyses evaluated change from baseline
in the International Restless Legs Scale (IRLS) total score and proportion
of responders on the investigator-rated Clinical Global Impression-
Improvement (CGI-I) scale at Week 12 last observation carried forward
(LOCF). Safety assessments included treatment-emergent adverse
events (TEAEs).
Results: The integrated modified intent-to-treat population comprised
671 subjects (GEn 600mg = 161; GEn 1200mg = 266; placebo = 244).
GEn 600mg improved mean [SD] IRLS total score versus placebo from
baseline to Week 12 LOCF (−13.8 [8.49] versus −9.3 [8.17]; adjusted
mean treatment difference [AMTD]: −4.3; 95% confidence interval [CI]:
−6.01, −2.52; P