Bioequivalence of TF3 and TF2 and Effect of Food on the PK of Tepotinib

NCT03629223 | Completed Phase 1 Results

• 2 other identifiers: MS200095_00442017-005056-29
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of the study was to demonstrate bioequivalence between the new tablet formulation (TF3, test treatment) and the tablet formulation used in clinical studies (TF2, reference treatment) and to investigate effect of food on pharmacokinetics (PK) of tepotinib.

Conditions

Healthy

Keywords

Tepotinib; Pharmacokinetics; Bioequivalence

Outcome Measures

Primary Outcomes (3)

• Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC 0-t) of Tepotinib

  Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

• Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib

  AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ lambda z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and lambda z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

• Part A, B and C: Maximum Observed Plasma Concentration (Cmax) of Tepotinib

  Cmax was obtained directly from the concentration versus time curve.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

Secondary Outcomes (8)

• Part A, B and C: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

• Part A, B and C: Terminal Half-Life (t1/2) of Tepotinib

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

• Part A, B and C: Apparent Total Body Clearance of Tepotinib From Plasma Following Oral Administration (CL/f)

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

• Part A, B and C: Apparent Volume of Distribution of Tepotinib During the Terminal Phase Following Extravascular Administration (Vz/f)

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144 and 168 hours post-dose on Day 1 of each treatment period

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

  Time from date of informed consent signature up to end of study (assessed up to 7 weeks)

Study Arms (6)

Part A: First Tepotinib TF2 then TF3

EXPERIMENTAL

Participants received a single oral dose of 500 milligrams (mg) Tepotinib tablet formulation 2 (TF2, reference treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib tablet formulation 3 (TF3, test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.

Drug: Tepotinib TF2; Drug: Tepotinib TF3

Part A: First Tepotinib TF3 then TF2

EXPERIMENTAL

Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.

Drug: Tepotinib TF2; Drug: Tepotinib TF3

Part B: First Tepotinib TF2 Fasted then TF2 Fed

EXPERIMENTAL

Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period.

Drug: Tepotinib TF2

Part B: First Tepotinib TF2 Fed then TF2 Fasted

EXPERIMENTAL

Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.

Drug: Tepotinib TF2

Part C: First Tepotinib TF3 Fasted then TF3 Fed

EXPERIMENTAL

Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fasting conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fed conditions. The washout period was 21 days between Day 1 of each period.

Drug: Tepotinib TF3

Part C: First Tepotinib TF3 Fed then TF3 Fasted

EXPERIMENTAL

Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 1 under fed conditions followed by a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of treatment period 2 under fasting conditions. The washout period was 21 days between Day 1 of each period.

Drug: Tepotinib TF3

Interventions

Tepotinib TF2 DRUG

Participants received a single oral dose of 500 mg Tepotinib TF2 under fasting or fed conditions in treatment period 1 or 2.

Part A: First Tepotinib TF2 then TF3; Part A: First Tepotinib TF3 then TF2; Part B: First Tepotinib TF2 Fasted then TF2 Fed; Part B: First Tepotinib TF2 Fed then TF2 Fasted

Tepotinib TF3 DRUG

Participants received single oral dose of 500 mg (2 x 250 mg)Tepotinib TF3 under fasting or fed conditions in treatment period 1 or 2.

Part A: First Tepotinib TF2 then TF3; Part A: First Tepotinib TF3 then TF2; Part C: First Tepotinib TF3 Fasted then TF3 Fed; Part C: First Tepotinib TF3 Fed then TF3 Fasted

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• Participation in a clinical study within 60 days prior to first drug administration
• Whole blood donation or loss of greater than 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts
• 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: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 14, 2018
• Study Start: August 23, 2018
• Primary Completion: January 25, 2019
• Study Completion: January 25, 2019
• Last Updated: October 10, 2023
• Results First Posted: October 10, 2023

Record last verified: 2023-10

Locations

DE (1)