Effect of a Proton Pump Inhibitor on the PK of Tepotinib

NCT03531762 | Completed Phase 1 Results

• 2 other identifiers: MS200095_00392017-002832-18
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study was investigated in healthy participants (i) the effect of omeprazole (proton pump inhibitor) co-administration on the single dose pharmacokinetics (PK) of tepotinib under fed conditions, and (ii) the effect of food on the single dose PK of tepotinib after co-administration of omeprazole and tepotinib. Furthermore, the study assessed the safety and tolerability of tepotinib alone and upon co-administration of omeprazole.

Conditions

Healthy

Keywords

Proton Pump Inhibitor; Omeprazole; Tepotinib; Non-small cell lung cancer (NSCLC); Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment A and Treatment C

  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, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C

  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, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)

• Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C

  Cmax was obtained directly from the concentration versus time curve.

  Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment C)

Secondary Outcomes (10)

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B

  Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B

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

  Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B

• Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B

  Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 5 for Treatment B

• Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C

  Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)

• Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C

  Pre-dose, 15, 30, 45, 60, 90 minutes, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96, 120 and 144 hour post-dose on Day 1 (for Treatment A) and on Day 5 (for Treatment B and C)

Study Arms (6)

Sequence 1: Treatment A-B-C

EXPERIMENTAL

Participants received single oral dose of 500 milligrams (mg) of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Drug: Tepotinib; Drug: Omeprazole

Sequence 2: Treatment A-C-B

EXPERIMENTAL

Participants received single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 1 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Drug: Tepotinib; Drug: Omeprazole

Sequence 3: Treatment B-A-C

EXPERIMENTAL

Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 3 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment C). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Drug: Tepotinib; Drug: Omeprazole

Sequence 4: Treatment B-C-A

EXPERIMENTAL

Participants received single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 1 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment B) followed by single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 2 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Drug: Tepotinib; Drug: Omeprazole

Sequence 5: Treatment C-A-B

EXPERIMENTAL

Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 2 (Treatment A) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 3 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 3 (Treatment B). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Drug: Tepotinib; Drug: Omeprazole

Sequence 6: Treatment C-B-A

EXPERIMENTAL

Participants received single oral dose of 500 mg Tepotinib in fed state on Day 5 of Treatment period 1 with 40 mg omeprazole once daily on Day 1 to 5 of Treatment period 1 (Treatment C) followed by single oral dose of 500 mg Tepotinib in fasted state on Day 5 of Treatment period 2 with 40 mg of omeprazole once daily on Day 1 to 5 of Treatment period 2 (Treatment B) followed by single oral dose of 500 mg of Tepotinib alone in fed state on Day 1 of Treatment period 3 (Treatment A). A washout period of at least 14 days was maintained between the Tepotinib single dose administrations.

Drug: Tepotinib; Drug: Omeprazole

Interventions

Tepotinib DRUG

Participants received single oral dose of 500 mg Tepotinib in Treatment A, B and C.

Sequence 1: Treatment A-B-C; Sequence 2: Treatment A-C-B; Sequence 3: Treatment B-A-C; Sequence 4: Treatment B-C-A; Sequence 5: Treatment C-A-B; Sequence 6: Treatment C-B-A

Omeprazole DRUG

Participants received omeprazole alone on Day 1 to 4 and co-administration of omeprazole with Tepotinib on Day 5 in Treatment B and C.

Sequence 1: Treatment A-B-C; Sequence 2: Treatment A-C-B; Sequence 3: Treatment B-A-C; Sequence 4: Treatment B-C-A; Sequence 5: Treatment C-A-B; Sequence 6: Treatment C-B-A

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 mass index (BMI) between 18.5 and 29.9 kilogram per meter square (kg/m\^2)
• Body weight between 50 to 100 kilogram (kg)

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)

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tepotinib; Omeprazole

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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: May 9, 2018
• First Posted: May 22, 2018
• Study Start: May 14, 2018
• Primary Completion: July 2, 2018
• Study Completion: July 2, 2018
• Last Updated: July 28, 2023
• Results First Posted: July 28, 2023

Record last verified: 2022-09

Locations

DE (1)