Dataset Information

SAGE-217, A Novel GABA_A Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.

ABSTRACT:

Background

SAGE-217, a novel ?-aminobutyric acid A (GABA_A) receptor positive allosteric modulator, was evaluated in phase I, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) studies to assess the safety and pharmacokinetics (PK) of SAGE-217 following administration as an oral solution.

Methods

In the SAD study, subjects were randomized 6:2 to a single dose of SAGE-217 or placebo. Doses ranged from 0.25 to 66 mg across nine cohorts. In the MAD study, subjects were randomized 9:3 and received SAGE-217 (15, 30, or 35 mg) or placebo once daily for 7 days. In both studies, PK, maximum tolerated dose (MTD; against predetermined criteria), safety, and tolerability were assessed.

Results

A total of 108 healthy volunteers enrolled in the studies-72 subjects in the SAD study and 36 subjects in the MAD study. SAGE-217 was orally bioavailable, with a terminal-phase half-life of 16-23 h and a t_max of approximately 1 h. The MTDs for the oral solution of SAGE-217 in the SAD and MAD studies were determined to be 55 and 30 mg daily, respectively. In both studies, SAGE-217 was generally well tolerated, and no serious adverse events (SAEs) were reported. Most AEs were mild, dose-dependent, transient, occurred around the t_max, and related to drug pharmacology.

Conclusions

SAGE-217 was generally well tolerated, and its PK profile was well characterized. Based on this profile, SAGE-217 has been advanced into multiple phase II clinical programs and pivotal studies of major depressive disorder and postpartum depression.

SUBMITTER: Hoffmann E

PROVIDER: S-EPMC6994455 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SAGE-217, A Novel GABA<sub>A</sub> Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.

Hoffmann Ethan E Nomikos George G GG Kaul Inder I Raines Shane S Wald Jeff J Bullock Amy A Sankoh Abdul J AJ Doherty James J Kanes Stephen J SJ Colquhoun Helen H

Clinical pharmacokinetics 20200101 1

<h4>Background</h4>SAGE-217, a novel γ-aminobutyric acid A (GABA<sub>A</sub>) receptor positive allosteric modulator, was evaluated in phase I, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) studies to assess the safety and pharmacokinetics (PK) of SAGE-217 following administration as an oral solution.<h4>Methods</h4>In the SAD study, subjects were randomized 6:2 to a single dose of SAGE-217 or placebo. Doses ranged from 0.25 to 66 mg across nine ...[more]

PMID: 31338688

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Dataset Information

SAGE-217, A Novel GABA_A Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.

Background

Methods

Results

Conclusions

Publications

SAGE-217, A Novel GABA<sub>A</sub> Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

SAGE-217, A Novel GABAA Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.

Background

Methods

Results

Conclusions

Publications

SAGE-217, A Novel GABA<sub>A</sub> Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

SAGE-217, A Novel GABA_A Receptor Positive Allosteric Modulator: Clinical Pharmacology and Tolerability in Randomized Phase I Dose-Finding Studies.