NCT07259330

To Determine the Effect of CYP Induction Following Administration of Nirogacestat in Healthy Adult Male Participants

A Phase 1, Single-Sequence, Two-Period Crossover, Open-Label Study to Determine the Potential Induction Effect of Multiple 100 mg BID Oral Doses of Nirogacestat on a Cocktail of CYP Probe Substrates CYP2B6 (Bupropion), CYP2C8 (Repaglinide), CYP2C9 (Flurbiprofen), CYP2C19 (Omeprazole), and CYP3A4 (Midazolam) in Healthy Males

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: SpringWorks Therapeutics, Inc. · Industry
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This study will evaluate the effects of nirogacestat 100 mg twice daily (BID) on the pharmacokinetics (PK) of a cytochrome P450 (CYP) cocktail.

Detailed description

This is a single-center, single-sequence crossover study to assess the potential induction effects of nirogacestat on the PK of probe substrates for CYPs (CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4) in healthy adult men. There will be a Screening Period of up to 33 days prior to Day -4. Eligible participants will be enrolled in the study and will complete a 3-day Lead-In Period, followed by an 18-day Treatment Period. A follow-up (FU) telephone call will be performed 26 to 28 days after the last dose of study treatment (Day 43 \[+2\]). During Screening, participants will sign the informed consent form prior to any study procedures being performed. Participants must satisfy all the inclusion and exclusion criteria to be eligible for study participation. Participants will be admitted to the clinical research unit (CRU) on Day -4 for check-in procedures and eligibility confirmation. Once eligibility is confirmed, participants will receive a CYP cocktail (CYP2B6 \[bupropion\], CYP2C8 \[repaglinide\], CYP2C9 \[flurbiprofen\], CYP2C19 \[omeprazole\], and CYP3A4 \[midazolam\]) on the morning of Day -3, following an overnight fast of at least 10 hours. The CYP cocktail will be administered orally. Beginning on Day 1 through Day 17, participants will be administered 100 mg nirogacestat orally BID. On Day 15, following an overnight fast of at least 10 hours, participants will also receive a single oral dose of the CYP cocktail in the morning immediately following the oral dose of nirogacestat. On all other days, nirogacestat can be administered with or without food. Study treatment will be administered orally. Assessments for safety along with serial samples of blood will be collected throughout the Lead-In and Treatment Period. Participants will remain domiciled at the CRU until all safety evaluations are completed on Day 18. Participants will complete a FU telephone visit on Day 43 (+2 days) for review of AEs/serious AEs and concomitant medications. Additional safety evaluations may be scheduled at the discretion of the investigator prior to the FU telephone visit.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	Nirogacestat	100 mg tablet Day 1 through Day 17
DRUG	Nirogacestat and Cocktail of CYP Specific Probe Substrates	Drug: Nirogacestat 100 mg tablet Day 1 through Day 17 and Drug: Cocktail of CYP Specific Probe Substrates administered Day 15.

Timeline

• Start date: 2025-10-27
• Primary completion: 2026-03-29
• Completion: 2026-03-29
• First posted: 2025-12-02
• Last updated: 2026-04-01

Locations

1 site across 1 country: Netherlands