HealthyPhase 1NCT03021642
Relative Bioavailability of Two Tepotinib Film-Coated Tablet Formulations in Healthy Volunteers
A Phase 1 study testing Tepotinib test (Treatment Period 1), Tepotinib reference (Treatment Period 2) and Tepotinib reference (Treatment Period 1) in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Tepotinib test (Treatment Period 1), Tepotinib reference (Treatment Period 2) and Tepotinib reference (Treatment Period 1)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- 31 Jan 2016to 31 Mar 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
Germany1 site
For Recruiting Locations outside US, please Contact Merck KGaA Communication Center
Darmstadt
About this study
Official title: A Phase I, Open-label, Randomized, Cross-over Trial to Investigate the Relative Bioavailability of Two Tepotinib Film-Coated Tablet Formulations in Healthy Volunteers
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
- Being tested
- Tepotinib test (Treatment Period 1), Tepotinib reference (Treatment Period 2), Tepotinib reference (Treatment Period 1), Tepotinib test (Treatment Period 2)
- Keywords
- Healthy volunteer, Tepotinib, Mesenchymal-epithelial transition factor, Translocated promoter region
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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)
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)
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)
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)
| Study group | Role | What they receive |
|---|---|---|
| First Tepotinib Test, Then Tepotinib Reference | Experimental | Not described Receives: Drug: Tepotinib test (Treatment Period 1); Drug: Tepotinib reference (Treatment Period 2) |
| First Tepotinib Reference, Then Tepotinib Test | Experimental | Not described Receives: Drug: Tepotinib reference (Treatment Period 1); Drug: Tepotinib test (Treatment Period 2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
AUC0-t at which the concentration was at or above LLOQ was calculated according to the mixed log linear trapezoidal rule.
Measured: 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)
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.
Measured: 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)
Cmax was obtained directly from the concentration versus time curve.
Measured: 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)
Tmax was obtained directly from the concentration versus time curve.
Measured: 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
t1/2 was defined as the time taken for the plasma concentration or the amount of drug in the body to be reduced by half.
Measured: 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 Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma
Apparent terminal rate constant was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Measured: 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
Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib
CL/f following oral administration was calculated as Dose/AUC0-inf, where AUC0-inf 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.
Measured: 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 Volume of Distribution (Vz/f) for Tepotinib
Vz/f is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f during the terminal phase was reported.
Measured: 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
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A)
%AUCextra was defined as a percentage of AUC0-inf obtained by extrapolation: %AUCextra = (1- [AUC0-t / AUC0-inf])*100. %AUCextra was reported in terms of percentage of AUC0-inf.
Measured: 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
Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib
Ratio of AUC0-inf of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of tepotinib was reported.
Measured: 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
Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib
Ratio of Cmax of metabolite (MSC2571109A or MSC2571107A) to Cmax of tepotinib was reported.
Measured: 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
Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug.
Measured: Baseline up to end of trial (up to Day 43)
Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters
Number of subjects with clinically significant change from baseline in vital signs, ECG and laboratory parameters were reported. Clinical Significance was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. The 12-lead ECGs were recorded after the subjects have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), RR, PR, QRS, QT and QTcB calculated by the Bazett formula. Laboratory investigation included hematology, biochemistry, urinalysis, and coagulation.
Measured: Baseline up to end of trial (up to Day 43)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2017 (estimated)
- Study start31 Jan 2016
- Primary completion31 Mar 2016
- Study completion31 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03021642
- Sponsor's protocol ID
- MS200095-0012
- Other IDs
- 2015-004369-95, 2015
- Status last verified
- Aug 2022
- First submitted
- 12 Jan 2017
- Last updated
- 24 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Randomized, Cross-over Trial to Investigate the Relative Bioavailability of Two Tepotinib Film-Coated Tablet Formulations in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03021642
- Acronym / sponsor ID
- MS200095-0012
- Conditions
- Healthy
- Keywords
- Healthy volunteer, Tepotinib, Mesenchymal-epithelial transition factor, Translocated promoter region
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 31 Jan 2016 (actual)
- Primary completion
- 31 Mar 2016 (actual)
- Study completion
- 31 Mar 2016 (actual)
- First posted
- 16 Jan 2017 (estimated)
- Results
- Posted 25 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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:
- Non-smoker (= 0 cigarettes, pipes, cigars, e-cigarettes, or others) for at least 6 months prior to screening
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) | Drug | First Tepotinib Test, Then Tepotinib Reference |
| 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) | Drug | First Tepotinib Test, Then Tepotinib Reference |
| 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) | Drug | First Tepotinib Reference, Then Tepotinib Test |
| 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) | Drug | First Tepotinib Reference, Then Tepotinib Test |
Primary outcome
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
Time frame: 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
AUC0-t was calculated according to the mixed log linear trapezoidal rule.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib
Time frame: 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
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.
Maximum Plasma Concentration Observed (Cmax) of Tepotinib
Time frame: 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
Cmax was obtained directly from the concentration versus time curve.
Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib
Time frame: 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) was obtained directly from the concentration versus time curve.
13 secondary outcomes
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib Metabolites (MSC2571109A and MSC2571107A)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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 Rate Constant (λz) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A) in Plasma
Time frame: 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
Total Body Clearance of Drug From Plasma (CL/f) for Tepotinib
Time frame: 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 Volume of Distribution (Vz/f) for Tepotinib
Time frame: 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
Extrapolated Area Under the Plasma Concentration-Time Curve From Time t to Infinity (%AUCextra) of Tepotinib and Metabolites (MSC2571109A and MSC2571107A)
Time frame: 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
Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Metabolite (MSC2571109A or MSC2571107A) to AUC0-inf of Tepotinib
Time frame: 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
Ratio of Maximum Plasma Concentration Observed (Cmax) of Metabolite (MSC2571109A or MSC2571107A) to Cmax of Tepotinib
Time frame: 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
Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation
Time frame: Baseline up to end of trial (up to Day 43)
Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Parameters
Time frame: Baseline up to end of trial (up to Day 43)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tepotinib test (Treatment Period 1), Tepotinib reference (Treatment Period 2) and Tepotinib reference (Treatment Period 1) in people with Healthy, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.