Tepotinib Drug-Drug Interaction Study With Carbamazepine in Healthy Participants

NCT ID: NCT05213481

Last Updated: 2024-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-15
• Study Completion Date: 2022-05-06

Brief Summary

The purpose of this study was to assess the effect of multiple doses of carbamazepine on single- dose tepotinib pharmacokinetics in healthy participants. Study details include: Study Duration: up to about 10 weeks; Treatment Duration: single dose of tepotinib on Days 1 and 26, 25 days of treatment with carbamazepine (Days 8 to 32); Visit Frequency: residence in the Clinical Research Unit from Days -1 to 4 and Days 25 to 29, ambulatory daily visits from Days 5 to 24 and 30 to 33, and one ambulatory visit on Day 39.

Conditions

Healthy

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tepotinib then Carbamazepine

Participants received a single oral dose of Tepotinib 500 milligrams (mg) on Day 1 and Day 26 in the morning under fed state followed by Carbamazepine 100, 200 or 300mg oral dose under fed state twice daily at the same time each day in the morning and evening from Days 8 to Day 32

Group Type: EXPERIMENTAL

Tepotinib

Intervention Type: DRUG

Participants received Tepotinib hydrochloride hydrate film-coated tablet once daily with food on Day 1 and Day 26 in the morning.

Carbamazepine

Intervention Type: DRUG

Carbamazepine 100 mg twice daily at Day 8 and 9, 200 mg twice daily at Day 10 and 11, 300 mg twice daily from Day 12 to 32.

Interventions

Tepotinib

Participants received Tepotinib hydrochloride hydrate film-coated tablet once daily with food on Day 1 and Day 26 in the morning.

Intervention Type: DRUG

Carbamazepine

Carbamazepine 100 mg twice daily at Day 8 and 9, 200 mg twice daily at Day 10 and 11, 300 mg twice daily from Day 12 to 32.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Overtly healthy participants as determined by medical evaluation, including no clinically significant abnormality identified by medical history, cardiac monitoring, physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion at Screening and Day -1
• Had a body weight within 50 and 100 kilogram (inclusive) and Body Mass Index (BMI) within the range greater than or equal (>=) 18.5 and less than or equal to (<=) 29.9 kilogram per meter square (inclusive) at Screening
• Male or female (not a Women of childbearing potential [WOCBP]). The Investigator confirms that each participant agrees to use appropriate contraception and barriers, if applicable. The contraception, barrier, and pregnancy testing requirements are below:
• Contraceptive use was consistent with local regulations on contraception methods for those participating in clinical studies. Male Participants: Agree to the following during the study intervention period and for at least 1 week after the last dose of study intervention: Refrain from donating fresh and unwashed sperm PLUS (+), either: Abstain from intercourse with a WOCBP.OR Use a male condom: When having sexual intercourse with a WOCBP, who is not currently pregnant, and instruct her to use a highly effective contraceptive method with a failure rate of < 1percent (%) per year
• Since a condom may break or leak. Not a WOCBP, confirmed at Screening, by fulfilling at least 1 of the following criteria: Females who are postmenopausal (age-related amenorrhea >= 12 consecutive months and increased Follicle-stimulating hormone (FSH)
• Documentation of irreversible surgical sterilization by hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy

Exclusion Criteria

• History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
• Participants with gall bladder removal or other relevant surgery of gastrointestinal tract (appendectomy is not considered as relevant)
• History of any malignancy except for adequately treated superficial basal cell carcinoma
• History of epilepsy
• Ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or excipients; history of anaphylaxis to drugs or serious allergic reactions leading to hospitalization or any other allergy reaction in general, which the Investigator considers may affect the safety of the participant and/or outcome of the study
• Any condition, including findings in the laboratory tests, medical history, or other Screening assessments, that in the opinion of the Investigator constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study's objectives, conduct, or evaluation
• Use of any prescribed medicine or over-the-counter drug or dietary supplement, including herbal remedies, vitamins, and minerals, antacids and dietary supplements such as fish oils within 2 weeks or 5 times the half-life of the respective drug, whichever is longer, prior to the first administration of study intervention

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

Nuvisan GmbH

Neu-Ulm, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200095_0051

Trial Awareness and Transparency website

https://www.merckgroup.com/en/company/contact-us/medinfo-contact-map.html

Medical Information Location Map - Med Info Contacts

Other Identifiers

2021-003546-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200095_0051

Identifier Type: -

Identifier Source: org_study_id