Phase 1, Single‐Center, Double‐Blind, Randomized, Placebo‐Controlled Studies of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of the Sirtuin 6 Activator SP‐624 in Healthy Adults
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: Sirtuin 6 activation is a novel epigenetic mechanism proposed for treatment of depression. Two Phase 1 studies, SP‐624‐101 and SP‐624‐102, examined the pharmacokinetics and safety of SP‐624, an orally active sirtuin 6 activator, in healthy adults. SP‐624‐101 was a single‐ascending‐dose study. In Part A, participants were randomized 6:2 to SP‐624 (single oral doses of 3, 10, or 30 mg) or placebo. Part B compared results in 8 participants receiving SP‐624 while fasting or after a high‐fat, high‐calorie breakfast. In SP‐624‐102, a multiple‐ascending‐dose study, participants were randomized 6:2 to SP‐624 (3 or 10 mg SP‐624 daily) or placebo for 5 days and 5:2 to SP‐624 20 mg daily or placebo for 10 days. At all doses, maximum concentration (Cmax) exceeded predicted target plasma concentrations of 3.28 ng/mL. Area under the concentration‐time curve and Cmax increased dose proportionally. A food effect resulted in significantly lower Cmax, later time to maximum concentration, and comparable AUC for fed versus fasting participants. No serious adverse events were observed. In SP‐624‐101 and SP‐624‐102, respectively, 3 (12%) and 5 (29%) SP‐624–treated participants experienced treatment‐emergent adverse events. SP‐624 was well tolerated and reached target concentrations in healthy adults, supporting progression of SP‐624 20 mg daily into Phase 2 studies of major depressive disorder.
DOI: 10.1002/cpdd.1488
Institution: BioVentures (United States)
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,620
OpenAlex ID: W4404725930