Phase 1
Completed N=12
Effect of Tepotinib on PK of CYP3A Substrate Midazolam
Healthy
Source: ClinicalTrials.gov NCT03628339 ↗
Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Jul 2023
Primary outcomePrimary: Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Midazolam — 107969; 109477 hour*picogram per milliliter (h*pg/mL)
Summary
The study investigated the effect of tepotinib on the pharmacokinetics (PK) of the Cytochrome P450 (CYP) 3A substrate midazolam determined from concentrations of midazolam and its main metabolite 1-hydroxymidazolam in healthy participants.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Midazolam |
107969; 109477 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam |
109285; 110550 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of Midazolam |
49172; 50954 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam) |
0.500; 0.508; 0.500; 0.508 | — |
| SECONDARY Elimination Half Life (t1/2) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam) |
5.52; 4.81; 6.34; 6.90 | — |
| SECONDARY Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Midazolam Metabolite (1-Hydroxymidazolam) |
30589; 32627 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam Metabolite (1-Hydroxymidazolam) |
31269; 33372 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Midazolam Metabolite (1-Hydroxymidazolam) |
14909; 15852 | — |
| SECONDARY Metabolic Ratio of Midazolam and Midazolam Metabolite (1-hydroxymidazolam) |
0.286; 0.302 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death |
1; 10; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes in Laboratory Values |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes in Vital Signs |
0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Healthy participants of non-child bearing potential
- Body weight between 50 to 100 kilogram (kg)
- Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m^2)
- Other protocol defined inclusion criteria could apply
Exclusion Criteria
- Participation in a clinical study within 60 days prior to first drug administration
- Whole blood donation or loss of greater than 450 milliliter (mL) within 60 days prior to first drug administration
- Any surgical or medical condition, or any other significant disease that could interfere with the study objectives, conduct, or evaluation
- Other protocol defined exclusion criteria could apply
Data sourced from ClinicalTrials.gov (NCT03628339). 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.