Tepotinib Drug-Drug Interaction Study With Carbamazepine in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is 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.

Official Title
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Phase I, Open-Label, Single-sequence, Cross-Over Study of the Effect of Multiple Doses of Carbamazepine on Single-Dose Tepotinib Pharmacokinetics in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: Tepotinib Hydrochloride Hydrate
* Drug: Carbamazepine


Participation Criteria
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Eligibility Criteria
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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 Have 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 will be 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 Other protocol defined inclusion criteria could apply 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 Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: This is a single sequence cross-over trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tepotinib then Carbamazepine<br>Participants will receive a single dose of tepotinib after standard breakfast on Day 1 and Day 26, along with carbamazepine twice daily at the same time each day in the morning and evening from Day 8 to Day 32. | Drug: Tepotinib Hydrochloride Hydrate<br>* Participants will receive Tepotinib hydrochloride hydrate film-coated tablet once daily with food on Day 1 and Day 26 in the morning.<br>Drug: Carbamazepine<br>* Participants will receive Carbamazepine tablet with break-line twice daily at the same time each day in the morning and evening from Day 8 to Day 32.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Plasma Concentrations of Tepotinib |  | Pre-dose up to 168 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrences of Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs by Severity |  | Baseline up to Day 39 | 
| Number of Participants With Abnormal Laboratory Parameters | Laboratory investigation included hematology, biochemistry, urinalysis, and coagulation. | Baseline up to Day 39 | 
| Absolute Values and Changes From Baseline for 12-lead Electrocardiograms (ECGs) Findings |  | Baseline up to Day 39 | 
| Number of Participants With Abnormal Vital Signs | Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate. | Baseline up to Day 39 | 
| Apparent Total Body Clearance (CL/f) of Tepotinib |  | Pre-dose up to 168 hours post-dose | 
| Apparent Volume of Distribution During Terminal Phase (VZ/f) of Tepotinib |  | Pre-dose up to 168 hours post-dose | 
| Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib |  | Pre-dose up to 168 hours post-dose | 
| Apparent Elimination Half Life (t1/2) of Tepotinib |  | Pre-dose up to 168 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical pharmacology, Metabolite, Induction of metabolism