Seaport Therapeutics, a clinical-stage biotherapeutics company, has announced positive results from its Phase I trial of SPT-300, an investigational allopregnanolone prodrug. The double-blind, single and multiple ascending dose study (NCT05129865) evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the oral prodrug in 99 healthy volunteers.
Phase I Trial Results
The Phase I data indicated that SPT-300 was well-tolerated, with somnolence being the most common adverse reaction, peaking within the first six to eight hours post-dosing. Notably, the study demonstrated that SPT-300 achieved therapeutically relevant blood levels up to nine times greater than those reported for orally administered unmodified allopregnanolone.
Electroencephalogram (EEG) analysis revealed increases in beta frequency power and a reduction in saccadic eye velocity approximately four hours after dosing, suggesting rapid pharmacodynamic activity. These findings support SPT-300's potential as a modulator of GABAA receptors.
Clinical Significance
SPT-300 is under investigation for a range of neurological and neuropsychiatric conditions, including major depressive disorder (MDD), anxiety, mood disorders, and Fragile X-associated tremor/ataxia syndrome. The Phase I results pave the way for a Phase IIb placebo-controlled study in MDD patients with or without anxious distress.
Tony Loebel, chief medical officer and president of clinical development at Seaport Therapeutics, stated, "Together with previous clinical efficacy data, the further analyses of the Phase I study demonstrate that these doses of SPT-300 are well-tolerated and have rapidly acting pharmacodynamic activity. This reinforces our confidence in SPT-300 as an oral modulator of GABAA receptors and as a potential rapidly acting antidepressant and anxiolytic agent."
Current Landscape of MDD Treatment
Major Depressive Disorder (MDD) affects millions worldwide, representing a significant global health burden. Current treatments, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), often have delayed onset of action and limited efficacy in some patients, highlighting the need for novel therapeutic options with rapid onset and improved tolerability.
Future Directions
Seaport Therapeutics is advancing SPT-300 into a Phase IIb clinical trial to further evaluate its efficacy and safety in patients with MDD. The company presented its Phase I findings at the American College of Neuropsychopharmacology (ACNP) Annual Meeting in Phoenix, Arizona.
