Evaluate the Effects of Famotidine or Rabeprazole on the PK of Nirogacestat

This is a phase 1, single-center, single-sequence crossover study to compare the PK, safety, and tolerability of nirogacestat alone or coadministered with famotidine or rabeprazole. This study will consist of 3 periods: Period 1 Nirogacestat Alone (Reference), Period 2 Nirogacestat and Famotidine (Test), and Period 3 Nirogacestat and Rabeprazole (Test).

There will be a screening period of up to 28 days prior to Day 1. Eligible participants will be enrolled in the study and will complete a 21-day Treatment Period. A follow-up (FU) telephone call will be performed approximately 26 days after discharge from the clinical research unit (CRU) on Day 47 (+2 days).

During screening, participants will sign the informed consent form (ICF) 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 CRU on Day -1 for check-in procedures and eligibility confirmation. Participants will remain domiciled at the CRU until Day 21 after the last PK sample is collected and safety evaluations are completed.

Participants will receive a single 150 mg dose of nirogacestat in the morning of Day 1 following an overnight fast of at least 10 hours once eligibility is confirmed. Study treatment (nirogacestat) will be administered by mouth (PO) followed by 240 mL of water; otherwise, additional fluids will be restricted from 1 hour predose until 2 hours postdose. A mouth check will be done to ensure the study treatment has been consumed. Participants will continue to fast for approximately 4 hours after administration of study treatment.

On Day 6, participants will be administered a single 150 mg dose of nirogacestat in the morning after an overnight fast of at least 10 hours. Study treatment (nirogacestat) will be administered PO followed by 240 mL of water; otherwise, additional fluids will be restricted from 1 hour predose until 2 hours postdose. Two hours after the administration of nirogacestat, participants will be administered 40 mg of famotidine PO followed by 240 mL of water; additional fluids will be restricted until 2 hours post dose of famotidine and participants will continue to fast for approximately 2 hours after administration of famotidine.

Beginning in the evening of Day 10 through Day 16, participants will be administered a single dose of rabeprazole each evening. On Day 17, following an overnight fast of at least 10 hours, participants will receive a single dose of nirogacestat in the morning. Study treatment will be administered PO followed by 240 mL of water; additional fluids will be restricted from 1 hour predose until 2 hours postdose; otherwise, participants will continue to fast for approximately 4 hours after administration of nirogacestat.