Effect of Tepotinib on the Pharmacokinetics (PK) of the P-glycoprotein (P-gp) Substrate Dabigatran Etexilate

• Status: Completed
• Trial end date: 2018-08-27
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Merck KGaA; Merck KGaA, Darmstadt, Germany
• Treatments: Dabigatran; Krestin; Tepotinib

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)

• A male participant must agree to use and to have his female partner of childbearing potential to use highly effective method of contraception

• Participant must have given written informed consent before any study-related activities

• All values for hematology, coagulation, and biochemistry tests of blood and urinalysis are within the normal range. Minor (solitary) non-clinically relevant deviation(s) are allowed as judged by the Investigator

• 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 > 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

• Supine systolic blood pressure (SBP) greater than (>) 140 millimeter of mercury (mmHg) or less than (<) 90 mmHg, diastolic blood pressure (DBP) > 90 or < 50 mmHg, and pulse rate > 90 or <50 beats per minute (bpm) at Screening and at admission on Day-1.

• 12-Lead electrocardiograms (ECG) showing a corrected QT interval per Fridericia's formula (QTcF) > 450 milliseconds (ms), PR > 215 ms, or QRS > 120 ms (at Screening)

• Creatinine clearance estimated glomerular filtration rate (eGFR) < 90 milliliter per minute (mL/min) (at Screening)

• Participants with gall bladder removal or other relevant surgery of gastrointestinal tract

• History of any malignancy

• History of epilepsy

• Ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or excipients

• Participants who in the Investigator's judgment were perceived as having an increased risk of bleeding

• Positive screen for alcohol or drugs of abuse (at Screening and Day -1)

• Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), and human immunodeficiency virus 1 and 2 antibodies (HIV1/HIV2 antibodies) (at Screening)

• Excessive consumption of xanthine-containing food or beverages before study drug administration until collection of last pharmacokinetic (PK) sample in each period (at Screening and Day -1)

• Receipt of any prescription or nonprescription medication within 14 days or 5 half-lives, before study drug administration

• Smoker or former smoker who stopped smoking less than 6 months before the time of the Screening Visit

• Intake of grapefruit, Seville orange, cranberry or juices of these 3 fruits, or St. John's Wort, from 14 days prior to Day -1

• Inability to communicate or cooperate with the Investigator

• Other factors, which in the opinion of the Investigator may interfere with study conduct (at Screening and Day -1 of first Period only)

• Legal incapacity or limited legal capacity

• Participants kept in detention

• Other protocol defined exclusion criteria could apply