Pharmacodynamic and pharmacokinetic profile of SM-1, a triple-drug combination to increase total sleep time.

OBJECTIVE: The primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM-1 after administration of a single oral dose to healthy volunteers in a placebo-controlled double-blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM-1 were also investigated. METHODS: Males and females 18-45 years of age received SM-1, a combination drug product comprised of diphenhydramine, zolpidem (delayed release), and lorazepam (delayed release). The pharmacokinetic profile of each drug was determined from blood samples. Sedative effects were assessed by visual analog scale, digit symbol substitution test, memory test, and quantitative electroencephalography. RESULTS: Similar number and severity of adverse events were observed following administration of SM-1 and placebo. Onset of sedation, as determined by subjective, performance, and electroencephalography measures, occurred 0.5-1 hr postdose, lasting about 7-7.5 hr. Plasma concentration curves for the two delayed-release components were altered compared with published data for unmodified drugs. Exposure values obtained with the combination product were in good agreement with published values of the drugs given individually. CONCLUSIONS: SM-1 was well tolerated and has pharmacologic activity starting within an hour of ingestion, lasting approximately 7-8 hr. Sedative activity was seen with subjective, psychomotor, and electroencephalography assays.

A randomized pharmacokinetic-pharmacodynamic evaluation of the potential biosimilar interferon beta-1a product, CinnoVex®.

BACKGROUND: The objective of the trial was to evaluate the bioequivalence of the interferon beta-1a (IFN beta-1a) biosimilar product candidate CinnoVex® with the reference product Avonex® by comparing the pharmacokinetics/pharmacodynamics (PK/PD), safety and immunogenicity of the two products in healthy subjects. METHODS: A total of 41 healthy subjects were randomized in a two-stage design to receive single doses of CinnoVex® and Avonex®. The primary PK endpoint was the area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-last). Additional PK parameters, safety and immunogenicity were evaluated as secondary endpoints. The main secondary PD endpoints were the areas under the concentration-time curves from time 0 to 168 hours (AUC0-168h) of the PD biomarkers. RESULTS: The two products demonstrated similar PK parameters, and the 90% confidence interval (CI) of the primary PK endpoint was within the bioequivalence acceptance limit. No serious adverse events were reported, and all adverse events (AE) were mild or moderate in severity. Anti-drug antibodies were not observed in any of the study participants. CONCLUSION: This study demonstrated PK/PD bioequivalence between CinnoVex® and Avonex®. The safety and tolerability profiles of both products were similar. CLINICAL TRIALS REGISTRATION: EudraCT Number 2016-000139-41.