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

MS200095_0032

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

2018-05-17

2018-08-27

2018-08-27

Completed

Early phase I

20

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ACTUAL'}}

2023-08-07