Trial Outcomes & Findings for Bioequivalence of TF3 and TF2 and Effect of Food on the PK of Tepotinib (NCT NCT03629223)

NCT ID: NCT03629223

Last Updated: 2023-10-10

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 66 participants
• Primary outcome timeframe: 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
• Results posted on: 2023-10-10

Participant Flow

Overall 142 participants were screened in this study. Out of which 66 participants were randomized into the study.

Participant milestones

Measure	Part A: First Tepotinib TF2 Then TF3 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.	Part A: First Tepotinib TF3 Then TF2 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.	Part B: First Tepotinib TF2 Fasted Then TF2 Fed 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.	Part B: First Tepotinib TF2 Fed Then TF2 Fasted 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.	Part C: First Tepotinib TF3 Fasted Then TF3 Fed 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.	Part C: First Tepotinib TF3 Fed Then TF3 Fasted 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.
Treatment Period 1 (21 Days) STARTED	20	20	6	8	6	6
Treatment Period 1 (21 Days) COMPLETED	20	18	6	6	6	6
Treatment Period 1 (21 Days) NOT COMPLETED	0	2	0	2	0	0
Treatment Period 2 (21 Days) STARTED	20	18	6	6	6	6
Treatment Period 2 (21 Days) COMPLETED	19	18	6	6	6	6
Treatment Period 2 (21 Days) NOT COMPLETED	1	0	0	0	0	0

Reasons for withdrawal

Measure	Part A: First Tepotinib TF2 Then TF3 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.	Part A: First Tepotinib TF3 Then TF2 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.	Part B: First Tepotinib TF2 Fasted Then TF2 Fed 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.	Part B: First Tepotinib TF2 Fed Then TF2 Fasted 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.	Part C: First Tepotinib TF3 Fasted Then TF3 Fed 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.	Part C: First Tepotinib TF3 Fed Then TF3 Fasted 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.
Treatment Period 1 (21 Days) Adverse Event	0	0	0	1	0	0
Treatment Period 1 (21 Days) Lost to Follow-up	0	0	0	1	0	0
Treatment Period 1 (21 Days) Benzodiazepines positive	0	1	0	0	0	0
Treatment Period 1 (21 Days) Toothache treatment	0	1	0	0	0	0
Treatment Period 2 (21 Days) Did not attend the ambulatory visits	1	0	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Part A: All Participants n=40 Participants All participants who received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) (1\*500 mg) or a single oral dose of Tepotinib TF3 (test treatment) (2\*250 mg tablet) on Day 1 of either treatment period 1 or 2 under fasted conditions.	Part B: All Participants n=14 Participants All participants who received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or 2 under fasted or fed conditions.	Part C: All Participants n=12 Participants All participants who received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or 2 under fasted or fed conditions.	Total n=66 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	66 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	61 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	65 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	38 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	64 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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

Population: Pharmacokinetic.(PK) Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; 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.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=38 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
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	16146 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 23.4	18645 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 21.0	12609 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 38.1	23457 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 25.1	17964 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 19.8	29307 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 25.0

PRIMARY outcome

Timeframe: 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

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; 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.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=38 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Part A, B and C: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC 0-inf) of Tepotinib	16728 ng*h/mL Geometric Coefficient of Variation 23.9	19316 ng*h/mL Geometric Coefficient of Variation 21.3	13037 ng*h/mL Geometric Coefficient of Variation 38.2	24443 ng*h/mL Geometric Coefficient of Variation 25.9	18447 ng*h/mL Geometric Coefficient of Variation 20.0	30118 ng*h/mL Geometric Coefficient of Variation 25.5

PRIMARY outcome

Timeframe: 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

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Cmax was obtained directly from the concentration versus time curve.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=38 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Part A, B and C: Maximum Observed Plasma Concentration (Cmax) of Tepotinib	253 ng/mL Geometric Coefficient of Variation 20.6	288 ng/mL Geometric Coefficient of Variation 22.5	199 ng/mL Geometric Coefficient of Variation 29.5	476 ng/mL Geometric Coefficient of Variation 19.6	280 ng/mL Geometric Coefficient of Variation 15.3	559 ng/mL Geometric Coefficient of Variation 17.0

SECONDARY outcome

Timeframe: 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

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=38 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Part A, B and C: Time to Reach the Maximum Plasma Concentration (Tmax) of Tepotinib	14.1 hours Interval 6.0 to 48.0	12.0 hours Interval 8.0 to 36.0	24.0 hours Interval 6.0 to 48.0	12.0 hours Interval 4.0 to 12.0	12.0 hours Interval 3.0 to 36.0	8.0 hours Interval 6.0 to 12.0

SECONDARY outcome

Timeframe: 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

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

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. Lambda z is the terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=38 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Part A, B and C: Terminal Half-Life (t1/2) of Tepotinib	31.8 hours Geometric Coefficient of Variation 17.8	30.9 hours Geometric Coefficient of Variation 15.3	30.8 hours Geometric Coefficient of Variation 11.6	30.0 hours Geometric Coefficient of Variation 12.9	29.2 hours Geometric Coefficient of Variation 14.7	29.9 hours Geometric Coefficient of Variation 14.5

SECONDARY outcome

Timeframe: 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

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=38 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Part A, B and C: Apparent Total Body Clearance of Tepotinib From Plasma Following Oral Administration (CL/f)	26.9 liter per hour Geometric Coefficient of Variation 23.9	23.3 liter per hour Geometric Coefficient of Variation 21.3	34.5 liter per hour Geometric Coefficient of Variation 38.2	18.4 liter per hour Geometric Coefficient of Variation 25.9	24.4 liter per hour Geometric Coefficient of Variation 20.0	14.9 liter per hour Geometric Coefficient of Variation 25.5

SECONDARY outcome

Timeframe: 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

Population: PK Analysis Set included participants without any relevant protocol deviations with respect to PK and absence of factors likely to affect comparability of PK results, with adequate trial medication compliance, who had valid primary endpoints for both treatments for Part A; and who had at least 3 post-dose concentration measurements for Part B; C.

Vz/f was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) is influenced by the fraction absorbed and was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f after oral dose is influenced by the fraction absorbed.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=38 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Part A, B and C: Apparent Volume of Distribution of Tepotinib During the Terminal Phase Following Extravascular Administration (Vz/f)	1232 liter Geometric Coefficient of Variation 28.5	1038 liter Geometric Coefficient of Variation 24.3	1531 liter Geometric Coefficient of Variation 40.8	797 liter Geometric Coefficient of Variation 27.0	1027 liter Geometric Coefficient of Variation 24.9	644 liter Geometric Coefficient of Variation 26.3

SECONDARY outcome

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

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

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 or 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 of each period 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	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=40 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	18 Participants	14 Participants	5 Participants	9 Participants	6 Participants	6 Participants

SECONDARY outcome

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

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

The laboratory measurements included hematology, blood chemistry and urinalysis. Number of participants with clinically significant abnormalities in laboratory values were reported. Clinically Significance was decided by investigator.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=40 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Number of Participants With Clinically Significant Abnormalities in Laboratory Values	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

The 12-lead ECG recordings were obtained after 5 minutes of rest in a semi-supine position. ECG recordings included rhythm, ventricular rate, PR interval, QRS duration, QT and QTc intervals. Number of participants with clinically significant abnormalities in 12-lead ECG findings were reported. Clinically significance was decided by investigator.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=40 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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

Population: The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

Vital sign assessment included blood pressure, pulse rate and body temperature. Number of participants with clinically significant abnormalities in vital signs were reported. Clinically significance was decided by investigator.

Outcome measures

Measure	Part A: TF2, Fasted n=38 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=40 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 Participants Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 Participants Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Number of Participants With Clinically Significant Abnormalities in Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Part A: TF2, Fasted

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Part A: TF3, Fasted

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Part B: TF2, Fasted

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part B: TF2, Fed

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Part C: TF3, Fasted

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part C: TF3, Fed

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A: TF2, Fasted n=38 participants at risk Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=40 participants at risk Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 participants at risk Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 participants at risk Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 participants at risk Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 participants at risk Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.1% 1/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

Other adverse events

Measure	Part A: TF2, Fasted n=38 participants at risk Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or of treatment period 2 under fasting conditions.	Part A: TF3, Fasted n=40 participants at risk Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fasted n=12 participants at risk Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part B: TF2, Fed n=14 participants at risk Participants received a single oral dose of 500 mg Tepotinib TF2 (reference treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.	Part C: TF3, Fasted n=12 participants at risk Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fasting conditions.	Part C: TF3, Fed n=12 participants at risk Participants received a single oral dose of 500 mg (2 x 250 mg) Tepotinib TF3 (test treatment) on Day 1 of either treatment period 1 or treatment period 2 under fed conditions.
Eye disorders Eye pain	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Eye disorders Visual impairment	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Abdominal pain	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	5.0% 2/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	21.4% 3/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	16.7% 2/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Abnormal faeces	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Diarrhoea	7.9% 3/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.5% 3/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	14.3% 2/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Faeces soft	5.3% 2/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Flatulence	5.3% 2/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Nausea	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Gastrointestinal disorders Toothache	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
General disorders Asthenia	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
General disorders Vessel puncture site pain	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Infections and infestations Influenza	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Infections and infestations Nasopharyngitis	7.9% 3/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Infections and infestations Viral upper respiratory tract infection	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Injury, poisoning and procedural complications Wound	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Musculoskeletal and connective tissue disorders Back pain	2.6% 1/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.1% 1/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	2.5% 1/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Nervous system disorders Headache	21.1% 8/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	12.5% 5/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	21.4% 3/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	41.7% 5/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Injury, poisoning and procedural complications Chest injury	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.1% 1/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Nervous system disorders Dizziness	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.1% 1/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Nervous system disorders Dysgeusia	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.1% 1/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Nervous system disorders Somnolence	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Renal and urinary disorders Micturition urgency	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	16.7% 2/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.1% 1/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	14.3% 2/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	16.7% 2/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	16.7% 2/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Surgical and medical procedures Radisectomy	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	7.1% 1/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Ear and labyrinth disorders Tinnitus	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Ear and labyrinth disorders Vertigo	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
General disorders Catheter site pain	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
General disorders Catheter site related reaction	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
General disorders Catheter site swelling	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
General disorders Fatigue	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Investigations Body temperature increased	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	16.7% 2/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Nervous system disorders Hypoaesthesia	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	16.7% 2/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Skin and subcutaneous tissue disorders Rash	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.
Renal and urinary disorders Pollakiuria	0.00% 0/38 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/40 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	8.3% 1/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/14 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.	0.00% 0/12 • Time from date of informed consent signature up to end of study (assessed up to 7 weeks) The Safety analysis set included all participants who had received at least 1 dose of planned study drug in the respective parts.

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: service@emdgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place