RECRUITING

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

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study will evaluate the effects of the H2 blocker famotidine or the PPI rabeprazole on the PK of nirogacestat in healthy male participants

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

Quick Facts

Study Start:2025-09-09

Study Completion:2025-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07171619

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 55 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
1. 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. 2. Participant is a male (assigned at birth) between 18 and 55 years of age (inclusive) at the time of informed consent. 3. 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. 4. 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. 5. 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. 6. 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. 7. Participant agrees to the following during the treatment periods and for at least 7 days after the last dose of study treatment: 1. Refrain from donating or preserving sperm; PLUS either 2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent. 3. 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. 8. Has sufficiently good venous access in at least one arm to confidently enable serial blood sampling.	1. 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. 2. Participant has a history or presence of any condition possibly affecting drug absorption (e.g., gastrectomy). 3. 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. 4. 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. 5. Participant has tested positive for active Helicobacter pylori (H. pylori) infection. 6. Participant has tested positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) or has a clinically significant infection. 7. 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. 8. 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. 9. Participant has averaged QT interval corrected using Fridericia formula (QTcF) results from valid triplicate ECGs \>450 msec at Screening and Day -1. 10. Participant has family history of long QT syndrome or of unexplained sudden death or drowning in a first-degree relative under age 50. 11. 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. 12. Participant has a positive alcohol breath test, positive cotinine test, or other positive drug screen test at Screening or Day -1. 13. 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. 14. Participant has received any vaccine within 14 days prior to the first dose of study treatment administration on Day 1. 15. Participant has received any CYP3A4 inhibitors or inducers within 21 days or 5 half-lives (whichever is longer) prior to Day 1. 16. 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. 17. 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. 18. 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. 19. 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. 20. 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. 21. Participant has a history of illicit drug abuse within the past 2 years prior to Screening. 22. 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. 23. 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. 24. Participant regularly consumes excessive amounts (defined as \>5 cups per day) of caffeine, xanthine-containing products, or energy drinks as judged by the investigator. 25. Participant has used tobacco- or nicotine-containing products within 2 months prior to Screening. 26. 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. 27. Participant has received blood products within the 60 days prior to Screening. 28. 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. 29. Participant is deemed unsuitable for this study in the opinion of the investigator for any additional reason, condition, or prior therapy.

Inclusion Criteria

Exclusion Criteria

1. 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.
2. Participant is a male (assigned at birth) between 18 and 55 years of age (inclusive) at the time of informed consent.
3. 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.
4. 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.
5. 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.
6. 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.
7. Participant agrees to the following during the treatment periods and for at least 7 days after the last dose of study treatment:
1. Refrain from donating or preserving sperm; PLUS either
2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
3. 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.
8. Has sufficiently good venous access in at least one arm to confidently enable serial blood sampling.

1. 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.
2. Participant has a history or presence of any condition possibly affecting drug absorption (e.g., gastrectomy).
3. 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.
4. 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.
5. Participant has tested positive for active Helicobacter pylori (H. pylori) infection.
6. Participant has tested positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) or has a clinically significant infection.
7. 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.
8. 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.
9. Participant has averaged QT interval corrected using Fridericia formula (QTcF) results from valid triplicate ECGs \>450 msec at Screening and Day -1.
10. Participant has family history of long QT syndrome or of unexplained sudden death or drowning in a first-degree relative under age 50.
11. 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.
12. Participant has a positive alcohol breath test, positive cotinine test, or other positive drug screen test at Screening or Day -1.
13. 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.
14. Participant has received any vaccine within 14 days prior to the first dose of study treatment administration on Day 1.
15. Participant has received any CYP3A4 inhibitors or inducers within 21 days or 5 half-lives (whichever is longer) prior to Day 1.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. Participant has a history of illicit drug abuse within the past 2 years prior to Screening.
22. 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.
23. 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.
24. Participant regularly consumes excessive amounts (defined as \>5 cups per day) of caffeine, xanthine-containing products, or energy drinks as judged by the investigator.
25. Participant has used tobacco- or nicotine-containing products within 2 months prior to Screening.
26. 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.
27. Participant has received blood products within the 60 days prior to Screening.
28. 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.
29. Participant is deemed unsuitable for this study in the opinion of the investigator for any additional reason, condition, or prior therapy.

Contacts and Locations

Study Contact

SpringWorks Clinical

CONTACT

877-279-4870

clinical@springworkstx.com

Principal Investigator

Mary Beth Brune, MD

PRINCIPAL_INVESTIGATOR

Medpace, Inc.

Study Locations (Sites)

Medpace

Cincinnati, Ohio, 45227

United States

Collaborators and Investigators

Sponsor: SpringWorks Therapeutics, Inc.

Mary Beth Brune, MD, PRINCIPAL_INVESTIGATOR, Medpace, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-09-09

Study Completion Date2025-11

Study Record Updates

Study Start Date2025-09-09

Study Completion Date2025-11

Terms related to this study

Additional Relevant MeSH Terms

Healthy