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

Merck KGaA (EMD Serono)

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Dabigatran Etexilate

Drug: Tepotinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT03492437

MS200095_0032

2017-004074-34 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment

20 patients

Sex

All

Ages

18 to 44 years old

Volunteers

Accepts Healthy Volunteers

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