Relative Bioavailability of Two Tepotinib Film-Coated Tablet Formulations in Healthy Volunteers

NCT ID: NCT03021642

Last Updated: 2022-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2016-03-31

Brief Summary

This is a Phase I, open label, randomized, crossover trial to investigate the relative bioavailability of tepotinib in healthy volunteers. Twenty-four volunteers will be randomized to one of the two treatment sequences: Sequence A: test, reference, Sequence B: reference, test. The reference treatment refers to the current Phase II film-coated tablet (5 * 100 milligram (mg) tepotinib film-coated tablets) and the test treatment to the new Phase III film-coated tablet (1 * 500 mg film-coated tepotinib tablet).

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

First Tepotinib Test, Then Tepotinib Reference

Group Type: EXPERIMENTAL

Tepotinib test (Treatment Period 1)

Intervention Type: DRUG

Subjects will be administered a single oral dose of test treatment of film-coated tepotinib tablet (1 \* 500 mg tablet) in Treatment period 1 (Day 1)

Tepotinib reference (Treatment Period 2)

Intervention Type: DRUG

Followed by a 21-day washout after Treatment period 1 (Day 1), subjects will be administered a single oral dose of reference treatment of film-coated tepotinib tablet (5 \* 100 mg tablet) in Treatment period 2 (Day 22)

First Tepotinib Reference, Then Tepotinib Test

Group Type: EXPERIMENTAL

Tepotinib reference (Treatment Period 1)

Intervention Type: DRUG

Subjects will be administered a single oral dose of reference treatment of film-coated tepotinib tablet (5 \* 100 mg tablet) in Treatment period 1 (Day 1)

Tepotinib test (Treatment Period 2)

Intervention Type: DRUG

Followed by a 21-day washout after Treatment period 1 (Day 1), subjects will be administered a single oral dose of test treatment of film-coated tepotinib tablet (1 \* 500 mg tablet) in Treatment period 2 (Day 22)

Interventions

Tepotinib test (Treatment Period 1)

Subjects will be administered a single oral dose of test treatment of film-coated tepotinib tablet (1 \* 500 mg tablet) in Treatment period 1 (Day 1)

Intervention Type: DRUG

Tepotinib reference (Treatment Period 2)

Followed by a 21-day washout after Treatment period 1 (Day 1), subjects will be administered a single oral dose of reference treatment of film-coated tepotinib tablet (5 \* 100 mg tablet) in Treatment period 2 (Day 22)

Intervention Type: DRUG

Tepotinib reference (Treatment Period 1)

Subjects will be administered a single oral dose of reference treatment of film-coated tepotinib tablet (5 \* 100 mg tablet) in Treatment period 1 (Day 1)

Intervention Type: DRUG

Tepotinib test (Treatment Period 2)

Followed by a 21-day washout after Treatment period 1 (Day 1), subjects will be administered a single oral dose of test treatment of film-coated tepotinib tablet (1 \* 500 mg tablet) in Treatment period 2 (Day 22)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy male and non-fertile, healthy female volunteers, 18 to 60 years of age (both inclusive) at the time of informed consent.
• Written informed consent given before any trial related activities are performed.
• Body weight greater than 50 kg and a body mass index (BMI) above 18 kilogram per meter square (kg/m^2) and below 30 kg/m^2 (BMI = weight [kg]/height [m^2]) at screening.
• Has vital signs in the following normal range:

• Oral body temperature: 35.5 to 37.5 degree celsius (°C)
• Blood pressure (BP) and pulse rate after at least 5 minutes of rest, measured in the supine position: Systolic blood pressure: 90 to 150 millimeter of mercury (mm Hg); Diastolic blood pressure: 40 to 90 mm Hg
• Pulse rate: 35 to 110 beats per minute (bpm)
• Non-smoker (= 0 cigarettes, pipes, cigars, e-cigarettes, or others) for at least 6 months prior to screening
• Women must be postmenopausal for at least 2 years, as confirmed by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) assessments performed at screening, or surgically sterile (that is, hysterectomy, oophorectomy). Pregnancy assessments will also be performed on female volunteers at screening and at admission.
• Males must agree to use and to have their female partners use highly effective medically acceptable methods of contraception during the period of participation in the trial and for at least 3 months after the last treatment administration. Men must refrain from donating sperm up to 3 months after the last treatment administration.
• Ability to understand the full nature and purpose of the trial, including possible risks and adverse effects; ability to cooperate with the Investigator and to comply with the requirements of the entire trial, including dietary restrictions.

Exclusion Criteria

• Any condition, including findings in the medical history, physical examination or in pretrial assessments that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the volunteer in the trial or that could interfere with the trial objectives, conduct or evaluation.
• Any clinically relevant abnormality in the results of the screening safety laboratory parameters. Specifically Alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin, Alkaline phosphatase (ALP), amylase, and lipase must not exceed the upper limit of the normal range.
• Any clinically relevant abnormality on the 12-lead electrocardiogram recording.
• Positive result from virology tests for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), or human immunodeficiency virus antibody (anti-HIV 1 and 2) at screening.
• History of clinically relevant renal, cardiovascular, and pulmonary disease, or endocrinology disorder.
• History of clinically relevant gastrointestinal disease, in particular pancreatic disease, cholecystitis, liver diseases or hepatic dysfunction.
• History of psychiatric or neurological disorders (depression, epilepsy etc.).
• Known hypersensitivity to tepotinib or its excipients.
• Presence or history of any serious allergy (requiring hospitalization or prolonged systemic treatment).
• Presence of drug or alcohol abuse, confirmed by positive test results for drugs of abuse or alcohol or history of drug and alcohol abuse in the past 3 years. Volunteers who consume more than 14 (female volunteers) or 21 (male volunteers) units of alcohol a week (unit = 1 glass of wine (125 milliliter [mL]) = 1 measure of spirits = ½ pint of beer).
• Loss or donation of more than 400 mL of blood within 12 weeks prior to entry into the trial.
• Participation in another clinical trial within the past 60 days.
• Any prescription or over the counter medication intake within 2 weeks prior to the first administration of tepotinib, including multivitamins and herbal products (St. John's wort), with the exception of acetaminophen and ibuprofen.
• Consumption of enzyme inducing or inhibiting herbal drugs, fruit juices and beverages (eg, grapefruit, grapefruit juice, Seville orange, quinine [tonic water], star fruit), and consumption of poppy seed within 3 days prior to the first administration of the investigational medicinal product.
• Excessive consumption of beverages containing xanthine (more than (>) 5 cups of coffee a day or equivalent) or inability to stop caffeine consumption while resident in the trial site. Continued use of caffeine (less than or equal to (=<)3 cups/day) or caffeine containing drinks or food, eg, coffee, tea, chocolate, Red Bull, or cola (1 caffeine unit is contained in the following items: 1 [6 ounces (oz)] cup of coffee, 2 [12 oz] cans of cola, 1 [12 oz] cup of tea, ½ [4 oz] cup of energy drink [eg, Red Bull], or 3 oz of chocolate).
• Legal incapacity or limited legal capacity.
• Unlikely to comply with the protocol requirements, instructions and trial related restrictions; eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial.
• Volunteer is the Investigator or Sub-Investigator, research assistant, pharmacist, trial coordinator, other staff or relative thereof directly involved in the conduct of the trial.
• Vulnerable volunteers (eg, persons kept in detention).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

For Recruiting Locations outside US, please Contact Merck KGaA Communication Center

Darmstadt, , Germany

Countries

Germany

Related Links

https://clinical-information.canada.ca/ci-rc/item/242300

Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)

Other Identifiers

2015-004369-95

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200095-0012

Identifier Type: -

Identifier Source: org_study_id