A Phase 1 Dose-Escalation, Food Effect, and Drug-Drug Interaction Study Evaluati...

연구 요약

A Phase 1 Dose-Escalation, Food Effect, and Drug-Drug Interaction Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the MALT1 Inhibitor, SGR-1505, in Healthy Volunteers.

Clinical pharmacology in drug development 학술지에 발표된 이 연구는 Gupta VK, Yoo B, Weiss D 외 연구팀이 수행하였습니다.

이 연구는 'A Phase 1 Dose-Escalation, Food Effect, and Drug-Drug Interaction Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the MALT1 Inhibitor, SGR-1505, in Healthy Volunteers.'에 대한 과학적 분석을 제공합니다.

핵심 내용

SGR-1505 is a novel small-molecule inhibitor of MALT1, a key mediator of NF-κB signaling implicated in the pathogenesis of B-cell malignancies. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of SGR-1505 in healthy volunteers. In this four-part, open-label study, 73 participants received single or multiple oral doses of SGR-1505 (25-225 mg). A food effect study assessed SGR-1505 exposure with and without a high-calorie, high-fat meal. The CYP3A4 drug-drug interaction potential of SGR-1505 was evaluated by co-administration with posaconazole, a strong CYP3A4 inhibitor. SGR-1505 was rapidly absorbed (median Tmax 2-4 h) with a dose-proportional increase in exposure up to 100 mg. Twice daily dosing at 100 mg over 10 days resulted in a 1.6-fold increase in both Cmax and AUC and a 2.5-fold increase in Ctrough compared to once daily dosing at 150 mg. A high-fat, high-calorie meal increased SGR-1505 Cmax 1.6-fold and AUC 1.3-fold compared to the fasted state. Co-administration with posaconazole increased SGR-1505 exposure 3-fold. SGR-1505 inhibited ex vivo stimulated T-cell derived IL-2 production in a concentration-dependent manner. Most adverse events were mild. Asymptomatic, reversible indirect hyperbilirubinemia occurred, consistent with inhibition of UGT1A1. SGR-1505 was well-tolerated and exhibited favorable pharmacokinetic and pharmacodynamic properties, supporting further clinical development.

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