Post-bedtime dosing with indiplon in adults and the elderly: results from two placebo-controlled, active comparator crossover studies in healthy volunteers.
OBJECTIVE
To assess the effects of post-bedtime dosing with indiplon on next-day function in adults and the elderly.


METHODS
Two randomized, double-blind, placebo-controlled crossover studies were conducted in two groups of healthy volunteers: an adult study (18-45 years) and an elderly study (65-80 years). In adults, a single post-bedtime dose of indiplon 10 mg and 20 mg was compared to placebo, with zolpidem 10 mg and zopiclone 7.5 mg included as controls. In the elderly, a single post-bedtime dose of indiplon 5 mg and 10 mg was compared to placebo, with zopiclone 3.75 mg included as a control. Next-day residual effects were evaluated in the morning at 4 and 6 h post-dose in adults, and 4, 6, and 8 h in the elderly, by a Visual Analog Scale of sleepiness (VAS-sleepiness), Digit Symbol Substitution Test (DSST), and the Symbol Copying Test (SCT).


RESULTS
In adults, there were no statistically significant differences between indiplon and placebo on the VAS-sleepiness, DSST, or SCT at any time-point for either dose. In contrast, a significant increase versus placebo in VAS-sleepiness was observed for both zopiclone (at 4 and 6 h post-dose; p < 0.0001 and p = 0.002, respectively) and zolpidem (at 4 h post-dose; p = 0.042). In the elderly, there were no statistically significant differences between indiplon 5 mg and placebo on the VAS-sleepiness, DSST, or SCT at any time-point. DSST was significantly reduced for indiplon 10 mg versus placebo at 4 h only (p = 0.022), compared with a significant reduction in DSST for zopiclone at both 4 and 8 h post-dose (p = 0.002 and p = 0.003, respectively). In adults, the overall incidence of adverse events was higher on zopiclone compared to indiplon, zolpidem, and placebo. In the elderly, the incidence of adverse events was similar for indiplon, zopiclone, and placebo. Potential limitations of the current study include recruitment of healthy volunteers and the use of a limited pharmacodynamic battery.


CONCLUSIONS
Indiplon, at doses of 10 mg in adults and 5 mg in the elderly, was not associated with next day residual sedation or impairment in simple cognitive and psychomotor tasks when administered during the night 4 h prior to awakening.
Farber
Robert H
RH
Neurocrine Biosciences, San Diego, CA, USA. rfarber@neurocrine.com
Burke
P Joshua
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053961:Azabicyclo Compounds / Q000008:administration & dosage / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011581:Psychological Tests; D011594:Psychometrics; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D012016:Reference Values; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects*; D013997:Time Factors; D000077334:Zolpidem
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011725:Pyridines; D013876:Thiophenes; C515050:zopiclone; D001569:Benzodiazepines; D000077334:Zolpidem; C469870:indiplon