New molecular entity: Gabapentin enacarbil extended-release tablets was approved by FDA as treatment for moderate-to-severe restless legs syndrome in adults.
Restless legs syndrome (RLS) is a disruptive neurologic disorder that affects up to 10% of Americans. RLS results in an irresistible urge to move the legs. On April 6, 2011, FDA approved gabapentin enacarbil extended-release tablets for the treatment of moderate-to-severe RLS in adults. Gabapentin enacarbil is not recommended for patients required to sleep during the daytime and remain awake at night.
Efficacy. Gabapentin enacarbil efficacy was established in two 12-week clinical studies in adults diagnosed with RLS using the International Restless Legs Syndrome (IRLS) Study Group Diagnostic Criteria (diagnostic criteria include, urge to move the legs usually accompanied by uncomfortable and unpleasant leg sensations during periods of rest or inactivity, symptoms are partially or totally relieved by movement and are worse or occur only in the evening or night). Patients with RLS secondary to other conditions (eg, pregnancy, renal failure, iron deficiency anemia) were excluded. In study 1, patients received 1,200 mg of gabapentin enacarbil (n=112) or placebo (n=108) taken once daily with food. In study 2, patients received 600 mg (n=112) and 1,200 mg (n=111) of gabapentin enacarbil or placebo (n=108) taken once daily with food. Efficacy was evaluated using the IRLS Rating Scale (including 10 items designed to assess the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence/sedation, and impact on activities of daily living and mood associated with RLS) and Clinical Global Impression of Improvement (CGI-I) scale. In both studies, statistically significant improvements between the gabapentin enacarbil 600 mg and placebo groups were observed at week 12 for both the IRLS Scale total score (-13.2 vs -8.8 and -13.0 vs -9.8, for study 1 and 2, respectively) and the proportion of responders as determined by the CGI-I scale (76% vs 39% and 73% vs 45%, for study 1 and 2, respectively).
Safety. In clinical trials, the most common adverse reactions (≥10% and at least 2 times the rate of placebo) seen with gabapentin enacarbil were somnolence/sedation and dizziness. The incidence of these adverse reactions was greater in these patients receiving 1,200 mg per day. Gabapentin enacarbil may cause significant driving impairment. As with other antiepileptic medications, gabapentin enacarbil may increase the risk of suicidal thoughts or behavior.