STUDY OBJECTIVES: The present single-dose, parallel-group, randomized, double-blind, placebo-controlled study is to evaluate the pharmacokinetics, tolerability and safety of zolpidem tartrate nasal spray (ZNS) as compared to placebo in healthy subjects. METHODS:Thirty-six healthy subjects participated in this study, with 19 male and 17 female subjects in 3 cohorts (12 subjects per cohort), who were randomly assigned to receive either an intranasal dose of ZNS 1.75 mg, 3.5 mg, 5.0 mg (n = 10 per dose), or an intranasal placebo (n = 2). Multiple venous blood samples were collected for pharmacokinetic analyses. RESULTS:Plasma zolpidem concentrations rapidly increased after intranasal ZNS 1.75, 3.5, and 5.0 mg with mean Tmax of 0.42, 0.76 and 0.50 h, respectively, followed by rapid decreases at all three doses. Cmax, AUC0-t, and AUC0-∞ were found to increase in a dose-proportional manner. Female subjects had generally higher AUC0-t, AUC0-∞, and lower weight-normalized clearance rate (CL/F) than male subjects. In this study, ZNS was safe and well tolerated over the evaluated dose range. There were no serious adverse events. CONCLUSIONS:Zolpidem was rapidly absorbed and eliminated after intranasal administration of ZNS. Dose proportionality was found at the doses ranged from 1.75 mg to 5.0 mg. Intranasal exposure of zolpidem was generally higher in female subjects than that in male subjects. It could be concluded that ZNS is safe and well tolerated over the evaluated range of intranasal doses.
RCT Entities:
STUDY OBJECTIVES: The present single-dose, parallel-group, randomized, double-blind, placebo-controlled study is to evaluate the pharmacokinetics, tolerability and safety of zolpidem tartrate nasal spray (ZNS) as compared to placebo in healthy subjects. METHODS: Thirty-six healthy subjects participated in this study, with 19 male and 17 female subjects in 3 cohorts (12 subjects per cohort), who were randomly assigned to receive either an intranasal dose of ZNS 1.75 mg, 3.5 mg, 5.0 mg (n = 10 per dose), or an intranasal placebo (n = 2). Multiple venous blood samples were collected for pharmacokinetic analyses. RESULTS: Plasma zolpidem concentrations rapidly increased after intranasal ZNS 1.75, 3.5, and 5.0 mg with mean Tmax of 0.42, 0.76 and 0.50 h, respectively, followed by rapid decreases at all three doses. Cmax, AUC0-t, and AUC0-∞ were found to increase in a dose-proportional manner. Female subjects had generally higher AUC0-t, AUC0-∞, and lower weight-normalized clearance rate (CL/F) than male subjects. In this study, ZNS was safe and well tolerated over the evaluated dose range. There were no serious adverse events. CONCLUSIONS:Zolpidem was rapidly absorbed and eliminated after intranasal administration of ZNS. Dose proportionality was found at the doses ranged from 1.75 mg to 5.0 mg. Intranasal exposure of zolpidem was generally higher in female subjects than that in male subjects. It could be concluded that ZNS is safe and well tolerated over the evaluated range of intranasal doses.
Authors: David J Greenblatt; Jerold S Harmatz; Thomas Roth; Nikhilesh N Singh; Margaret L Moline; Stephen C Harris; Ram P Kapil Journal: Clin Ther Date: 2013-03-28 Impact factor: 3.393