Efficacy and Safety of As-Needed, Post Bedtime Dosing with Indiplon in Insomnia Patients with Chronic Difficulty Maintaining Sleep

ObjectiveTo evaluate the efficacy and tolerability of immediate release indiplon capsules in patients with chronic insomnia using an "as-needed" dosing strategy in response to difficulty falling back to sleep following a middle of the night, nocturnal awakening.

MethodsAdult outpatients (N=264; 71% female; age, 46 years) who met DSM-IV criteria for primary insomnia, with average total sleep time (TST) < 6.5 hours and >8 nights in the past month with nocturnal awakenings, were randomized to 4 weeks of double-blind treatment with 10 mg or 20 mg indiplon capsules, or placebo. The primary endpoint was latency to sleep onset post-dosing after a middle of the night awakening (LSOpd). Secondary endpoints included patients' subjective assessment of total sleep time (sTSTpd). Next day residual effects were evaluated by a 100 mm Visual Analog Scale (VAS) rating of sleepiness.

ResultsBoth doses of indiplon significantly reduced LSOpd at all time-points. Compared to placebo (45.2 min), the 4-week least squares (LS) mean LSOpd was 36.5 min in the indiplon 10 mg group (P = 0.0023) and 34.4 min in the indiplon 20mg group (P < 0.0001). The 4-week LS mean sTSTpd was higher in the indiplon 10 mg group (253 min) and 20mg group (278 min) compared to placebo (229 min; P < 0.01 for both comparisons). There was no increase observed in VAS ratings of next-day sleepiness for either dose of indiplon when compared to placebo. Indiplon was well-tolerated at both doses.

ConclusionsPatients with chronic insomnia with nocturnal awakenings achieved significant and sustained improvement in sleep parameters while utilizing an as-needed post bedtime dosing strategy with indiplon capsules. Indiplon was well-tolerated, with no self-rated, next-day residual effects.