Phase 1
Completed N=18
Tepotinib Drug-Drug Interaction Study With Itraconazole in Healthy Participants
Healthy
Source: ClinicalTrials.gov NCT05203822 ↗
Enrolled (actual)
18
Serious AEs
0.0%
Results posted
Feb 2024
Primary outcomePrimary: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib — 18927; 23158 hours* nanograms per milliliter(h*ng/mL)
Summary
The purpose of this study was to assess the effect of multiple doses of itraconazole on single dose tepotinib pharmacokinetics in healthy participants. Study details include:
Study Duration: up to 48 days Treatment Duration: single dose of tepotinib on Days 1 and 12, 11 days of treatment with itraconazole (Days 8 to 18) Visit Frequency: residence in the Clinical Research Unit from Days -1 to 4 and Days 11 to 15, ambulatory daily visits from Days 5 to 10 and 16 to 20
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tepotinib |
18927; 23158 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Time of Last Measurable Concentration (AUC0-tlast) of Tepotinib |
18300; 21391 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Metabolite |
308; 313 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAES With Severity of Grade Greater or Equal to 3 |
14; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Meaningful Change From Baseline in Laboratory Values |
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 |
23.8; 19.4 | — |
| SECONDARY Apparent Volume of Distribution (Vz/f) for Tepotinib |
1102; 1148 | — |
| SECONDARY Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib |
8.00; 8.00 | — |
| SECONDARY Apparent Terminal Half-Life (t1/2) of Tepotinib in Plasma |
32.1; 40.9 | — |
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 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
- Not a WOCBP, confirmed at Screening, by fulfilling at least 1 of the following criteria: Females who are postmenopausal and documentation of irreversible surgical sterilization by hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and this protocol
- All values for hematology, coagulation, and biochemistry tests of blood and urinalysis within the normal range (at Screening and Day -1)
- 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
- Participation in the treatment phase of a clinical study within 60 days or 5 half-lives after last dosing of the previous study drug, whatever is longer, before administration of study drug
- Contraindication to itraconazole: ventricular dysfunction such as congestive heart failure or a history of congestive heart failure, drug interactions (examp
Data sourced from ClinicalTrials.gov (NCT05203822). 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.