Bioequivalence of 5 Tablets of 100 mg Versus 2 Tablets of 250 mg TF3 of Tepotinib

NCT04204902 | Completed Phase 1 Results

• 2 other identifiers: MS200095_00382019-003578-13
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigated the bioequivalence of the 100 milligrams (mg) and 250 mg dose strengths of tepotinib tablet formulation 3 (TF3) when administered at the same dose under fasted condition.

Conditions

Healthy

Keywords

Tepotinib; Bioequivalence; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Tepotinib

  Area under the plasma concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log linear trapezoidal rule (linear up/log down).

  Pre-dose, 0.25, 0.50, 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

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

  AUC0-inf was calculated as AUC0-t + AUC from time tlast extrapolated to infinity (AUCextra). AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/lambda z, where Clastpred was the predicted plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLOQ) and lambda z 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, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose

• Maximum Observed Plasma Concentration (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, 12, 16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 hours post-dose

Secondary Outcomes (6)

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

  Pre-dose, 0.25, 0.50, 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

• Terminal Half-Life (t1/2) of Tepotinib

  Pre-dose, 0.25, 0.50, 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

• Apparent Volume of Distribution During Terminal Phase (Vz/f) for Tepotinib

  Pre-dose, 0.25, 0.50, 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

• Apparent Total Body Clearance (CL/f) of Tepotinib

  Pre-dose, 0.25, 0.50, 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

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, TEAEs Leading to Discontinuation

  Baseline up to Day 59

Study Arms (2)

Test Treatment then Reference Treatment

EXPERIMENTAL

Participants received a single oral dose of test treatment of tepotinib TF3 (5 \* 100 mg) in treatment period 1 followed by a single oral dose of reference treatment of tepotinib TF3 (2 \* 250 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.

Drug: Tepotinib 100 mg; Drug: Tepotinib 250 mg

Reference Treatment then Test Treatment

EXPERIMENTAL

Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \* 250 mg) in treatment period 1 followed by a single oral dose of test treatment of tepotinib TF3 (5 \* 100 mg) in treatment period 2. The treatment periods were separated by 21 day washout period.

Drug: Tepotinib 100 mg; Drug: Tepotinib 250 mg

Interventions

Tepotinib 100 mg DRUG

Participants received a single oral dose of test treatment of tepotinib TF3 (5 \* 100 mg) in either treatment period 1 or 2.

Reference Treatment then Test Treatment; Test Treatment then Reference Treatment

Tepotinib 250 mg DRUG

Participants received a single oral dose of reference treatment of tepotinib TF3 (2 \* 250 mg) in either treatment period 1 or 2.

Reference Treatment then Test Treatment; Test Treatment then Reference Treatment

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 Healthcare KGaA, Darmstadt, Germany, an affiliate of 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

MeSH Terms

Interventions

tepotinib

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of 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: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 19, 2019
• Study Start: October 17, 2019
• Primary Completion: December 16, 2019
• Study Completion: December 16, 2019
• Last Updated: November 8, 2023
• Results First Posted: November 8, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)