Phase 1
Completed N=18
Tepotinib Drug-Drug Interaction Study With Carbamazepine in Healthy Participants
Healthy
Source: ClinicalTrials.gov NCT05213481 ↗
Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Mar 2024
Primary outcomePrimary: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib — 25101; 16738 hours* nanograms per milliliter(h*ng/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib |
25101; 16738 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Measurable Concentration (AUC0-tlast) of Tepotinib |
24069; 16272 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Tepotinib |
414; 372 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAES With Severity of Grade Greater or Equal to 3 |
17; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Meaningful Change From Baseline in Laboratory Values |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG) |
— | — |
| SECONDARY Number of Participants With Clinically Meaningful Change From Baseline in Vital Signs |
— | — |
| SECONDARY Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib |
17.9; 26.9 | — |
| SECONDARY Apparent Volume of Distribution (Vz/f) for Tepotinib |
801; 1157 | — |
| SECONDARY Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib |
8.02; 8.0 | — |
| SECONDARY Apparent Terminal Half-Life (t1/2) of Tepotinib in Plasma |
31.0; 29.8 | — |
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 ( = 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
Data sourced from ClinicalTrials.gov (NCT05213481). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.