Clinical trial NCT03531762: Effect of a Proton Pump Inhibitor on the PK of Tepotinib
Official title: Phase I, Open-label, Three-Period Crossover Study to Investigate the Effect of a Proton Pump Inhibitor (Omeprazole) on the PK of Tepotinib in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Proton Pump Inhibitor
Omeprazole
Tepotinib
Non-small cell lung cancer (NSCLC)
Pharmacokinetics
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-05-22
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This study was investigated in healthy participants (i) the effect of omeprazole (proton pump inhibitor) co-administration on the single dose pharmacokinetics (PK) of tepotinib under fed conditions, and (ii) the effect of food on the single dose PK of tepotinib after co-administration of omeprazole and tepotinib. Furthermore, the study assessed the safety and tolerability of tepotinib alone and upon co-administration of omeprazole.


Eligibility criteria: Inclusion Criteria:

* Healthy participants of non-child bearing potential
* Body mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m\^2)
* Body weight between 50 to 100 kilogram (kg)
* 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
measure: Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B
measure: Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
measure: Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
measure: Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Tepotinib in Treatments A, B and C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
measure: Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
measure: Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C
timeFrame: Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs
timeFrame: Baseline up to Day 4 for Treatment A and up to Day 8 for Treatment B and C
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: