Effect of a Proton Pump Inhibitor on the PK of Tepotinib

Sponsor
Merck KGaA, Darmstadt, Germany
Study ID
NCT03531762
Phase
PHASE1
Status
Completed

Conditions

  • Healthy

Eligibility Criteria

Sex
ALL
Age
18 Years - 55 Years
Healthy Volunteers
Accepted

Interventions

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

Study Details

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.

Key Dates

Start date
May 14, 2018
Status verified
Sep 2022
Primary completion
Jul 2, 2018
Completion
Jul 2, 2018

Study Design

Enrollment
12 participants (actual)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER

Arms

  • Experimental: Sequence 1: Treatment A-B-C
    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.
  • Experimental: Sequence 2: Treatment A-C-B
    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.
  • Experimental: Sequence 3: Treatment B-A-C
    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.
  • Experimental: Sequence 4: Treatment B-C-A
    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.
  • Experimental: Sequence 5: Treatment C-A-B
    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.
  • Experimental: Sequence 6: Treatment C-B-A
    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.

Primary Outcome Measure

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

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