HealthyPhase 1NCT03531762

Effect of a Proton Pump Inhibitor on the PK of Tepotinib

A Phase 1 study testing Tepotinib and Omeprazole in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Tepotinib and Omeprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteGermany
Study dates: 14 May 2018to 2 Jul 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

Nuvisan GmbH
Neu-Ulm, 89231

Other trials in Germany

About this study

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

Conditions: Healthy
Being tested: Tepotinib, Omeprazole
Keywords: Proton Pump Inhibitor, Omeprazole, Tepotinib, Non-small cell lung cancer (NSCLC), Pharmacokinetics
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TepotinibDrug
Participants received single oral dose of 500 mg Tepotinib in Treatment A, B and C.
OmeprazoleDrug
Participants received omeprazole alone on Day 1 to 4 and co-administration of omeprazole with Tepotinib on Day 5 in Treatment B and C.

Study groups in NCT03531762
Study group	Role	What they receive
Sequence 1: Treatment A-B-C	Experimental	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. Receives: Drug: Tepotinib; Drug: Omeprazole
Sequence 2: Treatment A-C-B	Experimental	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. Receives: Drug: Tepotinib; Drug: Omeprazole
Sequence 3: Treatment B-A-C	Experimental	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. Receives: Drug: Tepotinib; Drug: Omeprazole
Sequence 4: Treatment B-C-A	Experimental	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. Receives: Drug: Tepotinib; Drug: Omeprazole
Sequence 5: Treatment C-A-B	Experimental	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. Receives: Drug: Tepotinib; Drug: Omeprazole
Sequence 6: Treatment C-B-A	Experimental	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. Receives: Drug: Tepotinib; Drug: Omeprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C
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.
Measured: 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)
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C
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.
Measured: 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)
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C
Cmax was obtained directly from the concentration versus time curve.
Measured: 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 (10)

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 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.
Measured: 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
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B
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.
Measured: 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
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B
Cmax was obtained directly from the concentration versus time curve.
Measured: 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
Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Measured: 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)
Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C
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.
Measured: 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)
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Tepotinib in Treatments A, B and C
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.
Measured: 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)
Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Measured: 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)
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Measured: 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)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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.
Measured: Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs
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.
Measured: Baseline up to Day 4 for Treatment A and up to Day 8 for Treatment B and C

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 May 20182 Jul 2018

First posted22 May 2018
Study start14 May 2018
Primary completion2 Jul 2018
Study completion2 Jul 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03531762
Sponsor's protocol ID: MS200095_0039
Other IDs: 2017-002832-18, 2017
Status last verified: Sep 2022
First submitted: 9 May 2018
Last updated: 28 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03531762
Acronym / sponsor ID: MS200095_0039
Conditions: Healthy
Keywords: Proton Pump Inhibitor, Omeprazole, Tepotinib, Non-small cell lung cancer (NSCLC), Pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: 14 May 2018 (actual)
Primary completion: 2 Jul 2018 (actual)
Study completion: 2 Jul 2018 (actual)
First posted: 22 May 2018 (actual)
Results: Posted 28 Jul 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Sequence 1: Treatment A-B-C	Experimental	Drug: Tepotinib, Drug: OmeprazoleParticipants 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.
Sequence 2: Treatment A-C-B	Experimental	Drug: Tepotinib, Drug: OmeprazoleParticipants 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.
Sequence 3: Treatment B-A-C	Experimental	Drug: Tepotinib, Drug: OmeprazoleParticipants 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.
Sequence 4: Treatment B-C-A	Experimental	Drug: Tepotinib, Drug: OmeprazoleParticipants 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.
Sequence 5: Treatment C-A-B	Experimental	Drug: Tepotinib, Drug: OmeprazoleParticipants 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.
Sequence 6: Treatment C-B-A	Experimental	Drug: Tepotinib, Drug: OmeprazoleParticipants 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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TepotinibParticipants received single oral dose of 500 mg Tepotinib in Treatment A, B and C.	Drug	Sequence 1: Treatment A-B-C, Sequence 2: Treatment A-C-B, Sequence 3: Treatment B-A-C, Sequence 4: Treatment B-C-A, Sequence 5: Treatment C-A-B, Sequence 6: Treatment C-B-A
OmeprazoleParticipants received omeprazole alone on Day 1 to 4 and co-administration of omeprazole with Tepotinib on Day 5 in Treatment B and C.	Drug	Sequence 1: Treatment A-B-C, Sequence 2: Treatment A-C-B, Sequence 3: Treatment B-A-C, Sequence 4: Treatment B-C-A, Sequence 5: Treatment C-A-B, Sequence 6: Treatment C-B-A

Primary outcome

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C
Time frame: 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)
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.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C
Time frame: 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)
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.
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C
Time frame: 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)
Cmax was obtained directly from the concentration versus time curve.

10 secondary outcomes

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B
Time frame: 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
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B
Time frame: 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
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B
Time frame: 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
Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C
Time frame: 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)
Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C
Time frame: 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)
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Tepotinib in Treatments A, B and C
Time frame: 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)
Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C
Time frame: 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)
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C
Time frame: 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)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs
Time frame: Baseline up to Day 4 for Treatment A and up to Day 8 for Treatment B and C

Results and safety

Results posted to the registry on 28 Jul 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence 1: Treatment A-B-C	2	2
Sequence 2: Treatment A-C-B	2	2
Sequence 3: Treatment B-A-C	2	2
Sequence 4: Treatment B-C-A	2	2
Sequence 5: Treatment C-A-B	2	2
Sequence 6: Treatment C-B-A	2	2

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

Time frame: 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). Geometric mean (Geometric Coefficient of Variation). Unit: Hour*nanogram per milliliter (h*ng/mL)

Measure	Treatment A n = 12	Treatment C n = 12
Value	21722 (18.3)	23649 (19.5)

Treatment A vs Treatment C: Ratio of Geometric Least Square Mean: 108.87 (90% CI 101.20 to 117.13)

Population analysed: 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.

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

Measure	Treatment A n = 12	Treatment C n = 12
Value	23081 (19.8)	25343 (21.3)

Treatment A vs Treatment C: Ratio of Geometric Least Square Mean: 109.80 (90% CI 101.69 to 118.55)

Population analysed: 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.

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

Measure	Treatment A n = 12	Treatment C n = 12
Value	428 (12.2)	445 (21.1)

Treatment A vs Treatment C: Ratio of Geometric Least Square Mean: 104.10 (90% CI 92.93 to 116.61)

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment A	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
Treatment B	0 of 12 (0%)	3 of 12 (25%)	0 of 12
Treatment C	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Trial Awareness and Transparency websiteLink provided by the sponsor.
Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Responsible study director

Merck KGaA, Darmstadt, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tepotinib and Omeprazole in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: 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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03531762.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2023.