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PI‐39
Author(s) -
Corrigan B. W.,
Miller R.,
Chappell P. B.,
Farber R.,
Ouellet D.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.060
Subject(s) - nonmem , medicine , covariate , pharmacokinetics , mathematics , statistics
BACKGROUND/AIMS To describe the dose‐response relationship of indiplon on polysomnography‐derived total sleep time (TST). The impact of baseline, formulation (IR capsule, MR tablet), gender, time, and age (elderly, non‐elderly adults) was also evaluated. METHODS Data from 4 crossover Phase 2, and 2 parallel Phase 3 studies were pooled. Doses ranged from 5 to 40 mg. Dose‐response was modeled using a nonlinear mixed effects modeling approach (NONMEM Version V, UCSF). A predictive check (PC) was performed by simulating data for 100 replicate studies using the final model and comparing results to the observed data. RESULTS A total of 773 patients were included (5940 observations), with mean age of 59 years (18 to 85) years, 65% women, and 39% receiving the IR formulation. Baseline TST decreased with age (1.08 min per year), and was greater in women (1.9%). Response increased linearly with dose (0.811 min per mg for a baseline of 370 min) and was steeper in patients with low baseline values. PC showed that the model adequately described the response by dose and covariates. CONCLUSIONS TST decreased linearly as a function of dose. Drug response was governed to a large extent by baseline values. Age was an important determinant of TST. There was a small difference between genders with women having less severe baseline TST than men. Clinical Pharmacology & Therapeutics (2005) 79 , P17–P17; doi: 10.1016/j.clpt.2005.12.060