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

NCT03021642 | Completed Phase 1 Results

• 2 other identifiers: MS200095-00122015-004369-95
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Keywords

Healthy volunteer; Tepotinib; Mesenchymal-epithelial transition factor; Translocated promoter region

Outcome Measures

Primary Outcomes (4)

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) at Concentration at or Above Lower Limit of Quantitation (LLOQ) of Tepotinib

  AUC0-t was calculated according to the mixed log linear trapezoidal rule.

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib

  AUC0-inf was calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastcalc/λz, where Clastcalc was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and λz was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

• Maximum Plasma Concentration Observed (Cmax) of Tepotinib

  Cmax was obtained directly from the concentration versus time curve.

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

• Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib

  Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

Secondary Outcomes (13)

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

• Maximum Plasma Concentration Observed (Cmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

• Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

• Apparent Terminal Half-Life (t1/2) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma

  Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 24, 30, 36, 48, 54, 60, 72, 96, 120, 144, 168, 216, 288, 336, and 504 hours post-dose during Treatment Periods 1 and 2

Study Arms (2)

First Tepotinib Test, Then Tepotinib Reference

EXPERIMENTAL

Drug: Tepotinib test (Treatment Period 1); Drug: Tepotinib reference (Treatment Period 2)

First Tepotinib Reference, Then Tepotinib Test

EXPERIMENTAL

Drug: Tepotinib reference (Treatment Period 1); Drug: Tepotinib test (Treatment Period 2)

Interventions

Tepotinib test (Treatment Period 1) 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)

First Tepotinib Test, Then Tepotinib Reference

Tepotinib reference (Treatment Period 2) 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 Test, Then Tepotinib Reference

Tepotinib reference (Treatment Period 1) 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)

First Tepotinib Reference, Then Tepotinib Test

Tepotinib test (Treatment Period 2) 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)

First Tepotinib Reference, Then Tepotinib Test

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

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

Darmstadt, Germany

Location

Related Links

• 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)

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: January 16, 2017
• Study Start: January 31, 2016
• Primary Completion: March 31, 2016
• Study Completion: March 31, 2016
• Last Updated: August 24, 2022
• Results First Posted: January 25, 2019

Record last verified: 2022-08

Locations

DE (1)