HealthyPhase 1NCT07171619
Evaluate the Effects of Famotidine or Rabeprazole on the PK of Nirogacestat
A Phase 1 study testing Nirogacestat, Nirogacestat and Famotidine and Nirogacestat and Rabeprazole in people with Healthy, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 1 site in United States.
Trial summary
This study will evaluate the effects of the H2 blocker famotidine or the PPI rabeprazole on the PK of nirogacestat in healthy male participants Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Nirogacestat, Nirogacestat and Famotidine and Nirogacestat and Rabeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Aug 2025to 10 Nov 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participant understands the study procedures, is willing to comply with all study requirements and restrictions, and agrees to participate in the study by providing written informed consent as described in Appendix 1 of the protocol, prior to any study-related procedures being performed.
- Participant is a male (assigned at birth) between 18 and 55 years of age (inclusive) at the time of informed consent.
- Participant has a body mass index (BMI) ≥18.0 kg/m2 and ≤32.0 kg/m2 (inclusive) at Screening and a total body weight >50 kg.
- Participant is considered to be medically healthy, as determined by a responsible and experienced investigator, based on a clinical evaluation (including medical history, physical examination, clinical laboratory tests, vital sign measurements, and a 12-lead ECG performed, and the results of clinical chemistry, hematology, coagulation, and urinalysis carried out at Screening and Day -1.
- Participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels <1.5 × the upper limit of normal (ULN) at Screening and at Day -1.
- Participant has normal renal function (creatinine clearance ≥90 mL/min) as evidenced by normal estimated glomerular filtration rate (eGFR) measured by the CKD-EPI equation.
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- Participant agrees to the following during the treatment periods and for at least 7 days after the last dose of study treatment:
- Refrain from donating or preserving sperm; PLUS either
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
- OR
- Must agree to use a male condom when having sexual intercourse with women of childbearing potential (WOCBP). An additional form of contraception should also be used by the female partner if she is of childbearing potential.
- Has sufficiently good venous access in at least one arm to confidently enable serial blood sampling.
Who cannot join
- Participant has a history or presence of oncologic, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, ocular, endocrine, immunologic, dermatologic, musculoskeletal, neurologic, psychiatric, or other disease or condition or laboratory test abnormality that in the investigator's judgment poses a significant risk to the safety of the participant or the achievement of study objectives.
- Participant has a history or presence of any condition possibly affecting drug absorption (e.g., gastrectomy).
- Participant has a medical history or abnormal findings at Screening or Day -1 that the investigator judges may put at risk achieving the objectives of the study or protecting the safety of the participant.
- Participant has an acute illness with symptom or treatment that has started or persisted within 14 days prior to study treatment administration unless mild in severity and enrollment is approved by both investigator and sponsor's medical monitor.
- Participant has tested positive for active Helicobacter pylori (H. pylori) infection.
- Participant has tested positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) or has a clinically significant infection.
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- Participant has blood pressure (BP) that is ≥140 mmHg systolic or 90 mmHg diastolic following at least 5 minutes of rest in the supine position at Screening and Day -1. Additionally, BP that is <90 mmHg systolic or 45 mmHg diastolic following at least 5 minutes of rest at Screening and Day -1.
- Participant has heart rate (HR) that is <40 bpm or >100 bpm after resting in a supine position for 5 minutes at Screening and Day -1.
- Participant has averaged QT interval corrected using Fridericia formula (QTcF) results from valid triplicate ECGs >450 msec at Screening and Day -1.
- Participant has family history of long QT syndrome or of unexplained sudden death or drowning in a first-degree relative under age 50.
- Participant has an ECG waveform abnormality that interferes with QT/QTc interval measurement or interpretation. A participant with mild sinus arrhythmia or sparse isolated premature ventricular contractions (PVC) is eligible at the investigator's discretion.
- Participant has a positive alcohol breath test, positive cotinine test, or other positive drug screen test at Screening or Day -1.
- Participant has a positive nasopharyngeal rapid antigen test for SARS-CoV-2 on Day -1 or has had any known close contact with a person who tested positive for SARS-CoV-2 or with a COVID-19 patient within 2 weeks prior to admission.
- Participant has received any vaccine within 14 days prior to the first dose of study treatment administration on Day 1.
- Participant has received any CYP3A4 inhibitors or inducers within 21 days or 5 half-lives (whichever is longer) prior to Day 1.
- Participant has had concurrent use of long-acting gastric acid-reducing agents within 21 days of Day 1, including H2 blockers and PPIs, including over-the-counter agents.
- Participant has received any prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 3 weeks or 5 half-lives, if known (whichever is longer) prior to study treatment administration on Day 1.
- Participant has received an investigational product within 30 days or 5 times the half-lives, if known, of any drug used in the prior study (whichever is longer), or exposure to more than 3 new investigational agents within 12 months prior to study treatment administration on Day 1.
- Participant has a known hypersensitivity or intolerance to any of the study treatments, or excipients thereof, or a history of drug or other allergy that, in the opinion of the investigator or sponsor medical monitor, contraindicates their participation.
- Participant has a history of excessive intake of alcohol, defined as an average daily intake of >3 units, or an average weekly intake of >14 units (1 unit is equivalent to 1 can or bottle [250 mL] of beer, or 1 measure [35 mL] of spirits, or 1 glass [100 mL] of wine) in the last 6 months prior to Screening.
- Participant has a history of illicit drug abuse within the past 2 years prior to Screening.
- Participant has consumed red wine or any fruit juices (including but not limited to Seville oranges, grapefruit, grapefruit juice, star fruit, star fruit juice, pomelos, exotic citrus fruits, grapefruit hybrids) within 72 hours of Day -1, as outlined in Section 5.3.1.
- Participant has used caffeine or other xanthine-containing products (e.g., coffee, black tea, green tea, colas, cacao, guarana, guayusa, yerba mate) within 24 hours of Screening and Day -1.
- Participant regularly consumes excessive amounts (defined as >5 cups per day) of caffeine, xanthine-containing products, or energy drinks as judged by the investigator.
- Participant has used tobacco- or nicotine-containing products within 2 months prior to Screening.
- Participant has donated blood or had a loss of >450 mL of blood within 60 days or donation of plasma within 7 days prior to Screening.
- Participant has received blood products within the 60 days prior to Screening.
- Participant is unwilling to avoid strenuous or unaccustomed activity, sunbathing, or contact sports within 48 hours prior to admission to the CRU and until discharge from the CRU.
- Participant is deemed unsuitable for this study in the opinion of the investigator for any additional reason, condition, or prior therapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Single-Sequence, 3 Period Crossover, Open-Label Study to Determine the Effect of Rabeprazole or H2 Blocker Famotidine on the Pharmacokinetics of Nirogacestat in Healthy Adult Male Participants
This study will evaluate the effects of the H2 blocker famotidine or the PPI rabeprazole on the PK of nirogacestat in healthy male participants
Read the detailed description
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.
Participants will remain domiciled at the CRU until all safety evaluations are completed on Day 21.
Participants will complete a FU telephone visit on Day 47 (+2 days) for review of AEs/SAEs and concomitant medications.
- Conditions
- Healthy
- Being tested
- Nirogacestat, Nirogacestat and Famotidine, Nirogacestat and Rabeprazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NirogacestatDrug
Also called PF-03084014- GS (gamma secretase) inhibitor
oral dose of 150 mg nirogacestat
Nirogacestat and FamotidineDrug
Also called Histamine H2-Receptor Antagonist (H2 Blocker)
oral dose of 150 mg nirogacestat \& oral dose of 40 mg famotidine
Nirogacestat and RabeprazoleDrug
Also called Proton Pump Inhibitor (PPI)
oral dose of 150 mg nirogacestat and oral dose of 20 mg rabeprazole
| Study group | Role | What they receive |
|---|---|---|
| Period 1 - Nirogacestat Dose (Reference) | Active comparator | Nirogacestat will be administered, after at least a 10-hour fast, in the morning on Day 1, Day 6, and Day 17 Receives: Drug: Nirogacestat |
| Period 2 - Nirogacestat and Famotidine (Test) | Active comparator | Famotidine will be administered as an oral tablet 2 hours after the administration of nirogacestat on Day 6. Receives: Drug: Nirogacestat and Famotidine |
| Period 3 Nirogacestat and Rabeprazole (Test) | Active comparator | Rabeprazole will be administered as an oral tablet in the evenings on Day 10 through Day 16. Receives: Drug: Nirogacestat and Rabeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration-time curve from time zero to infinity of nirogacestat.
Serum AUCinf of nirogacestat.
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Maximum serum concentration (Cmax) of nirogacestat.
Serum Cmax of nirogacestat.
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Effect of a single 2-hour staggered dose of famotidine on the PK AUCinf of nirogacestat
Serum AUCinf of nirogacestat.
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Effect of a single 2-hour staggered dose of famotidine on the PK Cmax of nirogacestat
Serum Cmax of nirogacestat.
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Secondary outcomes (10)
Determine the effect of rabeprazole or famotidine on nirogacestat PK (AUClast) Area under the concentration-time curve from zero to the time last quantifiable concentration
Serum AUClast
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (Tmax) time of maximum concentration
Serum Tmax
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (T1/2) Terminal elimination half-life
Serum T1/2
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (CL/F) apparent clearance after oral dose
Serum CL/F
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (Vd/F) Apparent oral volume of distribution
Serum Vd/F
Measured: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
To evaluate the Adverse Events in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Safety assessments will include assessments of all adverse events (AEs) including any serious adverse events (SAEs) and graded using the most current version of the Common Terminology Criteria for Adverse Events CTCAE Version 5.0 condition-specific scale
Measured: Baseline through Day 21 and includes the Follow-up Phone Call
Number of Participants with Clinical Laboratory Tests Values Outside the Normal Reference Range
The laboratory test includes assessment of chemistry, hematology, coagulation, and urinalysis based on Investigator's decision/assessment.
Measured: Baseline (Day -1) through Day 21.
To evaluate the vital sign measurements in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Safety assessments will include assessments of all vital sign measurements of Heart Rate, Blood Pressure, Respirations and Body Temperature
Measured: Baseline (Day -1) through Day 21.
To evaluate ECG parameters in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Safety assessments will include assessments of all electrocardiograms (ECGs) to include heart rate and measures PR, QRS, QT, and QTcF and QT corrected using Bazett's formula (QTcB).
Measured: Baseline (Day -1) through Day 21.
To evaluate physical examination findings in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Safety assessments will include assessments of all physical examination findings to include assessments of the cardiovascular, dermatological, respiratory, gastrointestinal, skin, and neurological systems
Measured: Baseline (Day -1) through Day 21.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2025
- Study start21 Aug 2025
- Primary completion10 Nov 2025
- Study completion10 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- Three period Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mary Beth Brune, MD, Principal investigator, Medpace, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07171619
- Sponsor's protocol ID
- NIR-DT-107
- Status last verified
- Mar 2026
- First submitted
- 7 Aug 2025
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Single-Sequence, 3 Period Crossover, Open-Label Study to Determine the Effect of Rabeprazole or H2 Blocker Famotidine on the Pharmacokinetics of Nirogacestat in Healthy Adult Male Participants
- ClinicalTrials.gov ID
- NCT07171619
- Acronym / sponsor ID
- NIR-DT-107
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 21 Aug 2025 (actual)
- Primary completion
- 10 Nov 2025 (actual)
- Study completion
- 10 Nov 2025 (actual)
- First posted
- 12 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effects of the H2 blocker famotidine or the PPI rabeprazole on the PK of nirogacestat in healthy male participants
Detailed description
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.
Participants will remain domiciled at the CRU until all safety evaluations are completed on Day 21.
Participants will complete a FU telephone visit on Day 47 (+2 days) for review of AEs/SAEs and concomitant medications.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Three period Crossover
| Arm | Type | Receives |
|---|---|---|
| Period 1 - Nirogacestat Dose (Reference) | Active comparator | Drug: NirogacestatNirogacestat will be administered, after at least a 10-hour fast, in the morning on Day 1, Day 6, and Day 17 |
| Period 2 - Nirogacestat and Famotidine (Test) | Active comparator | Drug: Nirogacestat and FamotidineFamotidine will be administered as an oral tablet 2 hours after the administration of nirogacestat on Day 6. |
| Period 3 Nirogacestat and Rabeprazole (Test) | Active comparator | Drug: Nirogacestat and RabeprazoleRabeprazole will be administered as an oral tablet in the evenings on Day 10 through Day 16. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Participant understands the study procedures, is willing to comply with all study requirements and restrictions, and agrees to participate in the study by providing written informed consent as described in Appendix 1 of the protocol, prior to any study-related procedures being performed.
- Participant is a male (assigned at birth) between 18 and 55 years of age (inclusive) at the time of informed consent.
- Participant has a body mass index (BMI) ≥18.0 kg/m2 and ≤32.0 kg/m2 (inclusive) at Screening and a total body weight >50 kg.
- Participant is considered to be medically healthy, as determined by a responsible and experienced investigator, based on a clinical evaluation (including medical history, physical examination, clinical laboratory tests, vital sign measurements, and a 12-lead ECG performed, and the results of clinical chemistry, hematology, coagulation, and urinalysis carried out at Screening and Day -1.
- Participant has alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels <1.5 × the upper limit of normal (ULN) at Screening and at Day -1.
Key exclusion criteria (29 listed)
- Participant has a history or presence of oncologic, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, ocular, endocrine, immunologic, dermatologic, musculoskeletal, neurologic, psychiatric, or other disease or condition or laboratory test abnormality that in the investigator's judgment poses a significant risk to the safety of the participant or the achievement of study objectives.
- Participant has a history or presence of any condition possibly affecting drug absorption (e.g., gastrectomy).
- Participant has a medical history or abnormal findings at Screening or Day -1 that the investigator judges may put at risk achieving the objectives of the study or protecting the safety of the participant.
- Participant has an acute illness with symptom or treatment that has started or persisted within 14 days prior to study treatment administration unless mild in severity and enrollment is approved by both investigator and sponsor's medical monitor.
- Participant has tested positive for active Helicobacter pylori (H. pylori) infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NirogacestatAlso: PF-03084014- GS (gamma secretase) inhibitororal dose of 150 mg nirogacestat | Drug | Period 1 - Nirogacestat Dose (Reference) |
| Nirogacestat and FamotidineAlso: Histamine H2-Receptor Antagonist (H2 Blocker)oral dose of 150 mg nirogacestat \& oral dose of 40 mg famotidine | Drug | Period 2 - Nirogacestat and Famotidine (Test) |
| Nirogacestat and RabeprazoleAlso: Proton Pump Inhibitor (PPI)oral dose of 150 mg nirogacestat and oral dose of 20 mg rabeprazole | Drug | Period 3 Nirogacestat and Rabeprazole (Test) |
Primary outcome
Area under the concentration-time curve from time zero to infinity of nirogacestat.
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Serum AUCinf of nirogacestat.
Maximum serum concentration (Cmax) of nirogacestat.
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Serum Cmax of nirogacestat.
Effect of a single 2-hour staggered dose of famotidine on the PK AUCinf of nirogacestat
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Serum AUCinf of nirogacestat.
Effect of a single 2-hour staggered dose of famotidine on the PK Cmax of nirogacestat
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Serum Cmax of nirogacestat.
10 secondary outcomes
Determine the effect of rabeprazole or famotidine on nirogacestat PK (AUClast) Area under the concentration-time curve from zero to the time last quantifiable concentration
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (Tmax) time of maximum concentration
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (T1/2) Terminal elimination half-life
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (CL/F) apparent clearance after oral dose
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
Determine the effect of rabeprazole or famotidine on nirogacestat PK (Vd/F) Apparent oral volume of distribution
Time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose
To evaluate the Adverse Events in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Time frame: Baseline through Day 21 and includes the Follow-up Phone Call
Number of Participants with Clinical Laboratory Tests Values Outside the Normal Reference Range
Time frame: Baseline (Day -1) through Day 21.
To evaluate the vital sign measurements in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Time frame: Baseline (Day -1) through Day 21.
To evaluate ECG parameters in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Time frame: Baseline (Day -1) through Day 21.
To evaluate physical examination findings in healthy male participants after a single 150 mg dose of nirogacestat administered with and without rabeprazole or famotidine
Time frame: Baseline (Day -1) through Day 21.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Individual participant dataSharing planned: No. We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary Beth Brune, MD principal investigator
Medpace, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nirogacestat, Nirogacestat and Famotidine and Nirogacestat and Rabeprazole in people with Healthy, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the concentration-time curve from time zero to infinity of nirogacestat. (time frame: Serial blood samples will be collected to determine concentrations of nirogacestat (in serum) on Day 1, Day 6, and Day 17 predose (-30 minutes) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours postdose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.