Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Anticoagulants

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Amino Acids

Dabigatran

Tepotinib

polysaccharide-K

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Enzyme Inhibitors

Serine

Participants received single oral dose of Dabigatran etexilate on Day 1 of Treatment period 1 and co-administration of Dabigatran with Tepotinib on Day 8 of Treatment period 2.

Dabigatran Etexilate

Participants received single oral dose of Tepotinib for 8 days in Treatment period 2.

Medical Responsible

This study investigated the effect of Tepotinib on the pharmacokinetics (PK) of the p-glycoprotein (P-gp) probe substrate Dabigatran etexilate.

Effect of Tepotinib on the PK of the P-gp Substrate Dabigatran Etexilate

Phase I, Open-label, Single Sequence, Two-Period Study to Evaluate the Effect of Tepotinib on P-gp by Investigating the PK of the P-gp Probe Substrate Dabigatran Etexilate in Healthy Subjects

AUC0-t was calculated according to the mixed log linear trapezoidal rule.

AUC0-inf was calculated as AUC0-t plus (+) AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/Lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log-linear regression line for Lambda z determination at which the measured plasma concentration is at or above Lower limit of quantification (LLOQ).

Cmax was obtained directly from the concentration versus time curve.

Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.

Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f after oral dose was influenced by the fraction absorbed.

The AUC from time tlast extrapolated to infinity given as percentage of AUC0-inf. AUCextra% = (AUCextra /AUC0-inf)\*100.

Adverse event (AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event (SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs.

Number of participants with clinically significant change in laboratory values were reported. Clinical significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, virology, drugs of abuse, hormones, urinalysis, and coagulation.

Number of participants with clinically significant change in 12-lead ECG were reported. Clinical significance was decided by the investigator. The 12-lead ECGs were recorded after the participant have rested for at least 5 minutes in supine position.

Number of participants with clinically significant change in vital signs were reported. Clinical significance was decided by the investigator. Vital signs included body temperature, blood pressure, and pulse rate.

Merck KGaA, Darmstadt, Germany

Participants received a single oral dose of 75 milligrams (mg) dabigatran etexilate capsule on Day 1 under fed state in treatment period 1.

All participants who received 75 mg Dabigatran Etexilate in treatment period 1, received oral dose of 500 mg tepotinib film-coated tablets from Day 1 to 8 under fed state along with 75 mg dabigatran etexilate on Day 8 of treatment period 2.

Tepotinib + Dabigatran

All participants who received a single oral dose of 75 mg dabigatran etexilate capsule in treatment period 1 and 500 mg tepotinib (500 mg) film coated tablet from Day 1 to 8 along with 75 mg dabigatran etexilate Capsule in treatment period 2 under fed state.

All Participants

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Communication Center

Pharmacokinetic (PK) analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

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 Total Dabigatran

PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Dabigatran

Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran

Time to Reach Maximum Plasma Concentration (Tmax) of Total Dabigatran

Elimination Half Life (t1/2) of Total Dabigatran

Apparent Clearance (CL/f) of Total Dabigatran

Apparent Volume of Distribution During Terminal Phase (Vz/f) of Total Dabigatran

Percentage of Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Total Dabigatran

Treatment-emergent Adverse Events (TEAEs)

Serious TEAEs

The safety analysis set included all participants who received at least 1 dose of the planned investigational medicinal product (IMP).

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

The safety analysis set included all participants who received at least 1 dose of the planned IMP.

Spots Global Cancer Trial Database for Effect of Tepotinib on the PK of the P-gp Substrate Dabigatran Etexilate

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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