Effect of Tepotinib on the PK of the P-gp Substrate Dabigatran Etexilate
Condition: Healthy
Intervention: Dabigatran Etexilate; Tepotinib
Intervention description: 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.; Participants received single oral dose of Tepotinib for 8 days in Treatment period 2.
Intervention MeSH terms: Tepotinib; Dabigatran
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 44 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Non-small cell lung cancer (NSCLC); P-glycoprotein; Tepotinib; Dabigatran Etexilate

Summary:

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

Eligibility 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