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Trial record 10 of 333 for:    DABIGATRAN

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

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ClinicalTrials.gov Identifier: NCT03492437
Recruitment Status : Completed
First Posted : April 10, 2018
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

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

Condition or disease Intervention/treatment Phase
Healthy Drug: Dabigatran Etexilate Drug: Tepotinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Phase I, Open-label, Single Sequence, Two-Period Study to Evaluate the Effect of Tepotinib on P-Glycoprotein by Investigating the Pharmacokinetics of the P-Glycoprotein Probe Substrate Dabigatran Etexilate in Healthy Subjects
Actual Study Start Date : May 17, 2018
Actual Primary Completion Date : August 27, 2018
Actual Study Completion Date : August 27, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dabigatran, Then Tepotinib followed by Dabigatran+Tepotinib
Dabigatran etexilate in treatment period 1 followed by tepotinib alone for 7 days and then tepotinib co-administered with Dabigatran in treatment period 2. Two treatment periods will be separated by a 3-day wash-out period.
Drug: Dabigatran Etexilate
Participants will receive 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.

Drug: Tepotinib
Participants will receive single oral dose of Tepotinib for 8 days in Treatment period 2.




Primary Outcome Measures :
  1. Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]
  2. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]
  3. Maximum Observed Plasma Concentration (Cmax) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]

Secondary Outcome Measures :
  1. Time to Reach Maximum Plasma Concentration (Tmax) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]
  2. Elimination Half Time (t1/2) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]
  3. Apparent Clearance (CL/f) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]
  4. Apparent Volume of Distribution During Terminal Phase (Vz/f) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]
  5. Percentage of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Dabigatran [ Time Frame: Pre-dose up to 72 hours post-dose ]
  6. Occurrence of Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Day 15 ]
  7. Number of Participants With Clinically Significant Changes in Laboratory Assessments, 12-lead Electrocardiogram (ECG) Findings and Vital Signs [ Time Frame: Baseline up to Day 15 ]
    Number of participants with clinically significant changes will be reported.



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Ages Eligible for Study:   18 Years to 44 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03492437


Locations
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Germany
Nuvisan GmbH
Neu-Ulm, Germany, 89231
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany

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Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT03492437     History of Changes
Other Study ID Numbers: MS200095_0032
2017-004074-34 ( EudraCT Number )
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck KGaA, Darmstadt, Germany:
Non-small cell lung cancer (NSCLC)
P-glycoprotein
Tepotinib
Dabigatran Etexilate
Additional relevant MeSH terms:
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Dabigatran
polysaccharide-K
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents