This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective: To assess the efficacy and tolerability of the nondopaminergic agent XP13512/GSK1838262 in adults with moderate to severe primary restless legs syndrome (RLS).
Methods: Patient Improvements in Vital Outcomes following Treatment in Restless Legs Syndrome I was a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of XP13512 1,200 mg or placebo taken once daily at 5:00 pm with food. Coprimary endpoints were mean change from baseline International Restless Legs Scale (IRLS) total score and proportion of investigator-rated responders (very much improved or much improved on the Clinical Global Impression–Improvement scale) at week 12 (last observation carried forward). Tolerability was assessed using adverse events, vital signs, and clinical laboratory parameters.
Results: A total of 222 patients were randomized (XP13512 = 114, placebo = 108) and 192 patients (XP13512 = 100, placebo = 92) completed the study. At week 12, the mean change from baseline IRLS total score was greater with XP13512 (−13.2) compared with placebo (−8.8). Analysis of covariance, adjusted for baseline score and pooled site, demonstrated a mean treatment difference of −4.0 (95% confidence interval [CI], −6.2 to −1.9; p = 0.0003). More patients treated with XP13512 (76.1%) were responders compared with placebo (38.9%; adjusted OR 5.1; 95% CI, 2.8 to 9.2; p < 0.0001). Significant treatment effects for both coprimary measures were identified at week 1, the earliest time point measured. The most commonly reported adverse events were somnolence (XP13512 27%, placebo 7%) and dizziness (XP13512 20%, placebo 5%), which were mild to moderate in intensity and generally remitted.
Conclusions: XP13512 1,200 mg, taken once daily, significantly improved restless legs syndrome (RLS) symptoms compared with placebo and was generally well tolerated in adults with moderate to severe primary RLS.
Glossary
- AE=
- adverse event;
- ANCOVA=
- analysis of covariance;
- CGI-I=
- Clinical Global Impression–Improvement;
- CI=
- confidence interval;
- ESS=
- Epworth Sleepiness Scale;
- IRLS=
- International Restless Legs Scale;
- LOCF=
- last observation carried forward;
- LS=
- least squares;
- MITT=
- modified intent-to-treat population;
- MOS=
- Medical Outcomes Study;
- NNT=
- numbers needed to treat;
- OR=
- odds ratio;
- PghSD=
- Pittsburgh Sleep Diary;
- PSQ=
- post-sleep questionnaire;
- RLS=
- restless legs syndrome;
- RLSQoL=
- RLS Quality of Life;
- SAE=
- serious adverse events;
- SOS=
- Sudden Onset of Sleep questionnaire;
- TST=
- total sleep time;
- WASO=
- wake time after sleep onset.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.