Trial Outcomes & Findings for Effect of a Proton Pump Inhibitor on the PK of Tepotinib (NCT NCT03531762)
NCT ID: NCT03531762
Last Updated: 2023-07-28
Results Overview
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.
COMPLETED
PHASE1
12 participants
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)
2023-07-28
Participant Flow
Overall, 28 participants were screened for the study. Out of which 12 participants were randomized into the study.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (8-12 Days)
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Treatment Period 1 (8-12 Days)
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Treatment Period 1 (8-12 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2 (8-12 Days)
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Treatment Period 2 (8-12 Days)
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Treatment Period 2 (8-12 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (8-12 Days)
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Treatment Period 3 (8-12 Days)
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Treatment Period 3 (8-12 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of a Proton Pump Inhibitor on the PK of Tepotinib
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=12 Participants
All participants who received single oral dose of 500 mg of Tepotinib alone in fed state (Treatment A) or in fasted state with 40 mg omeprazole (Treatment B) or in fed state with 40 mg omeprazole (Treatment C) in either Treatment period 1, Treatment Period 2 or Treatment period 3.
|
|---|---|
|
Age, Continuous
|
48 Years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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)Population: Pharmacokinetic (PK) Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
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.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 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
|
21722 Hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 18.3
|
23649 Hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 19.5
|
—
|
PRIMARY outcome
Timeframe: 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)Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
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.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment A and Treatment C
|
23081 h*ng/mL
Geometric Coefficient of Variation 19.8
|
25343 h*ng/mL
Geometric Coefficient of Variation 21.3
|
—
|
PRIMARY outcome
Timeframe: 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)Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment A and Treatment C
|
428 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 12.2
|
445 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 21.1
|
—
|
SECONDARY outcome
Timeframe: 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 BPopulation: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
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.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Tepotinib in Treatment B
|
16220 h*ng/mL
Geometric Coefficient of Variation 24.4
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 BPopulation: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
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.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib in Treatment B
|
17412 h*ng/mL
Geometric Coefficient of Variation 27.2
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 BPopulation: PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration.
Cmax was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Tepotinib in Treatment B
|
227 ng/mL
Geometric Coefficient of Variation 25.7
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib in Treatments A, B and C
|
8.0 Hours
Interval 6.0 to 12.0
|
12.0 Hours
Interval 4.0 to 48.0
|
8.0 Hours
Interval 6.0 to 12.0
|
SECONDARY outcome
Timeframe: 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)Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Apparent Terminal Half-life (t1/2) of Tepotinib in Treatments A, B and C
|
32.9 hour
Interval 23.2 to 40.5
|
30.7 hour
Interval 22.4 to 50.2
|
31.7 hour
Interval 25.8 to 48.0
|
SECONDARY outcome
Timeframe: 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)Population: None of the participants were analyzed and no data was collected for this outcome as Tlag was included in the Statistical Analysis Plan and protocol in error and this parameter was not relevant for decision making. Hence, no analysis was conducted for this outcome.
Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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)Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Apparent Total Body Clearance (CL/f) of Tepotinib in Treatments A, B and C
|
19.5 Liter per hour (L/h)
Geometric Coefficient of Variation 19.8
|
25.8 Liter per hour (L/h)
Geometric Coefficient of Variation 27.2
|
17.8 Liter per hour (L/h)
Geometric Coefficient of Variation 21.3
|
SECONDARY outcome
Timeframe: 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)Population: The PK Analysis Set included all participants who received at least 1 dose of IMP, had no clinically important protocol deviations or important events affecting PK, and provided at least 1 measurable post dose concentration
Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Tepotinib in Treatments A, B and C
|
912 Liters
Geometric Coefficient of Variation 18.4
|
1181 Liters
Geometric Coefficient of Variation 21.7
|
860 Liters
Geometric Coefficient of Variation 21.9
|
SECONDARY outcome
Timeframe: Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and CPopulation: The Safety Analysis Set included all participants who received at least 1 dose of planned IMP and had 1 subsequent safety assessment.
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether/not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. 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. An AE was considered as 'treatment emergent' if it occurred after the first drug administration or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both serious TEAEs and non-serious TEAEs.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
1 Participants
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 4 for Treatment A and up to Day 8 for Treatment B and CPopulation: The Safety Analysis Set included all participants who received at least 1 dose of planned IMP and had 1 subsequent safety assessment.
The laboratory measurements included hematology, biochemistry, virology, drugs of abuse, hormones, and urinalysis. ECG recordings included PR, QRS, RR, QT and corrected QT intervals (QTcF). Vital sign assessment included blood pressure, pulse rate, body temperature. Number of participants with clinically significant abnormalities in laboratory parameters, 12-lead ECG findings, vital signs were reported. Clinically significance was decided by investigator.
Outcome measures
| Measure |
Treatment A
n=12 Participants
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 Participants
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs
Laboratory Parameters
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs
12-lead Electrocardiogram (ECG) Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Changes in Laboratory Parameters, 12-lead Electrocardiogram (ECG) Findings and Vital Signs
Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Treatment A
Treatment B
Treatment C
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=12 participants at risk
Participants received single oral dose of Tepotinib 500 mg alone in fed state on Day 1 in either Treatment period 1 or 2 or 3.
|
Treatment B
n=12 participants at risk
Participants received single oral dose of 500 mg of Tepotinib in fasted state on Day 5 with 40 mg of omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
Treatment C
n=12 participants at risk
Participants received single oral dose of 500 mg of Tepotinib in fed state on Day 5 with 40 mg omeprazole once daily on Day 1 to 5 of either Treatment period 1 or 2 or 3.
|
|---|---|---|---|
|
Eye disorders
Conjunctival cyst
|
8.3%
1/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
8.3%
1/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
8.3%
1/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
8.3%
1/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
8.3%
1/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
8.3%
1/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
8.3%
1/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
0.00%
0/12 • Baseline up to Day 7 for Treatment A and up to Day 11 for Treatment B and C
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place