Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Gastrointestinal Agents

All Drugs and Chemicals

Antineoplastic Agents

Omeprazole

Proton Pump Inhibitors

Tepotinib

Antacids

Anti-Ulcer Agents

Enzyme Inhibitors

Participants received single oral dose of 500 milligrams (mg) of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Participants received single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Participants received single oral dose of 500 mg Tepotinib in Treatment A, B and C.

Participants received omeprazole alone on Day 1 to 4 and co-administration of omeprazole with Tepotinib on Day 5 in Treatment B and C.

Medical Responsible

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.

Effect of a Proton Pump Inhibitor on the PK of Tepotinib

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

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/Lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Cmax was obtained directly from the concentration versus time curve.

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.

Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.

An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether/not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs.

The laboratory measurements included hematology, biochemistry, virology, drugs of abuse, hormones, and urinalysis. ECG recordings included PR, QRS, RR, QT and corrected QT intervals (QTcF). Vital sign assessment included blood pressure, pulse rate, body temperature. Number of participants with clinically significant abnormalities in laboratory parameters, 12-lead ECG findings, vital signs were reported. Clinically significance was decided by investigator.

Merck KGaA, Darmstadt, Germany

Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.

Treatment A

Participants received single oral dose of 500 mg of Tepotinib in fasted state on Day 5 with 40 mg of omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.

Treatment B

Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.

Treatment C

All participants who received single oral dose of 500 mg of Tepotinib alone in fed state (Treatment A) or in fasted state with 40 mg omeprazole (Treatment B) or in fed state with 40 mg omeprazole (Treatment C) in either Treatment period 1, Treatment Period 2 or Treatment period 3.

Entire Study Population

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Communication Center

Pharmacokinetic (PK) Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C

The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C

Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B

PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.

Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B

The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration

Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C

Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C

None of the participants were analyzed and no data was collected for this outcome as Tlag was included in the Statistical Analysis Plan and protocol in error and this parameter was not relevant for decision making. Hence, no analysis was conducted for this outcome.

Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Tepotinib in Treatments A, B and C

Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C

Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C

The Safety Analysis Set included all participants who received at least 1 dose of planned IMP and had 1 subsequent safety assessment.

Spots Global Cancer Trial Database for Effect of a Proton Pump Inhibitor on the PK of Tepotinib

Trial Identification

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Interventions

Study Description

Keywords

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