Trial Outcomes & Findings for Bioequivalence Study of Coated Cesol Tablet Formulation Versus Biltricide (NCT NCT04314037)

NCT ID: NCT04314037

Last Updated: 2021-08-13

Results Overview

Cmax was obtained directly from the concentration versus time curve.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Results posted on

2021-08-13

Participant Flow

36 participants were randomized in 1:1 ratio to the two treatment sequences: Sequence 1 (First Cesol, Then Biltricide, Then Cesol and Then Biltricide) and Sequence 2 (First Biltricide, Then Cesol, Then Biltricide and Then Cesol).

Participant milestones

Participant milestones
Measure
First Cesol, Then Biltricide, Then Cesol and Then Biltricide
Participants received first single oral dose of 1200 milligrams (mg) (two 600 mg film-coated tablets) Cesol (Test 1) on Day 1 in treatment period 1 followed by first single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 1) on Day 8 in treatment period 2 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 2) on Day 15 in treatment period 3 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 2) on Day 22 in treatment period 4 under fed conditions. A washout period of 7 days was maintained between 4 treatment periods.
First Biltricide, Then Cesol, Then Biltricide and Then Cesol
Participants received first single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 1) on Day 1 in treatment period 1 followed by first single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 1) on Day 8 in treatment period 2 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 2) on Day 15 in treatment period 3 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 2) on Day 22 in treatment period 4 under fed conditions. A washout period of 7 days was maintained between 4 treatment periods.
Treatment Period 1
STARTED
18
18
Treatment Period 1
COMPLETED
18
18
Treatment Period 1
NOT COMPLETED
0
0
Treatment Period 2
STARTED
18
18
Treatment Period 2
COMPLETED
17
18
Treatment Period 2
NOT COMPLETED
1
0
Treatment Period 3
STARTED
17
18
Treatment Period 3
COMPLETED
16
17
Treatment Period 3
NOT COMPLETED
1
1
Treatment Period 4
STARTED
16
17
Treatment Period 4
COMPLETED
16
17
Treatment Period 4
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
First Cesol, Then Biltricide, Then Cesol and Then Biltricide
Participants received first single oral dose of 1200 milligrams (mg) (two 600 mg film-coated tablets) Cesol (Test 1) on Day 1 in treatment period 1 followed by first single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 1) on Day 8 in treatment period 2 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 2) on Day 15 in treatment period 3 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 2) on Day 22 in treatment period 4 under fed conditions. A washout period of 7 days was maintained between 4 treatment periods.
First Biltricide, Then Cesol, Then Biltricide and Then Cesol
Participants received first single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 1) on Day 1 in treatment period 1 followed by first single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 1) on Day 8 in treatment period 2 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 2) on Day 15 in treatment period 3 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 2) on Day 22 in treatment period 4 under fed conditions. A washout period of 7 days was maintained between 4 treatment periods.
Treatment Period 2
Adverse Event
1
0
Treatment Period 3
Protocol Violation
1
0
Treatment Period 3
Adverse Event
0
1

Baseline Characteristics

Bioequivalence Study of Coated Cesol Tablet Formulation Versus Biltricide

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
First Cesol, Then Biltricide, Then Cesol and Then Biltricide
n=18 Participants
Participants received first single oral dose of 1200 milligrams (mg) (two 600 mg film-coated tablets) Cesol (Test 1) on Day 1 in treatment period 1 followed by first single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 1) on Day 8 in treatment period 2 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 2) on Day 15 in treatment period 3 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 2) on Day 22 in treatment period 4 under fed conditions. A washout period of 7 days was maintained between 4 treatment periods.
First Biltricide, Then Cesol, Then Biltricide and Then Cesol
n=18 Participants
Participants received first single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 1) on Day 1 in treatment period 1 followed by first single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 1) on Day 8 in treatment period 2 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Biltricide (Reference 2) on Day 15 in treatment period 3 followed by second single oral dose of 1200 mg (two 600 mg film-coated tablets) Cesol (Test 2) on Day 22 in treatment period 4 under fed conditions. A washout period of 7 days was maintained between 4 treatment periods.
Total
n=36 Participants
Total of all reporting groups
Age, Continuous
32 years
STANDARD_DEVIATION 10.8 • n=5 Participants
37 years
STANDARD_DEVIATION 10.8 • n=7 Participants
34 years
STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Male
18 Participants
n=5 Participants
18 Participants
n=7 Participants
36 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
18 Participants
n=5 Participants
18 Participants
n=7 Participants
36 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 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
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
White
18 Participants
n=5 Participants
17 Participants
n=7 Participants
35 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The Pharmacokinetic (PK) Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Cmax was obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ)
421 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 118.3
415 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 129.1
425 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 98.3
459 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 129.5

PRIMARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

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 (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemic-Praziquantel (Rac-PZQ)
894 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 114.6
873 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 118.9
886 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 105.7
964 hours*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 124.8

SECONDARY outcome

Timeframe: Baseline up to Day 27

Population: The safety analysis set included all participants who were administered any dose of any study intervention.

Adverse event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: 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. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
TEAEs
6 Participants
6 Participants
7 Participants
7 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
Treatment related TEAEs
6 Participants
6 Participants
7 Participants
6 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 27

Population: The safety analysis set included all participants who were administered any dose of any study intervention.

Severity of TEAEs were graded using Qualitative Toxicity Scale, as follows: Mild: Participant is aware of the event or symptom, but the event or symptom is easily tolerated; Moderate: Participant experiences sufficient discomfort to interfere with or reduce his or her usual level of activity; Severe: Significant impairment of functioning: the participant is unable to carry out his or her usual activities. Number of participants with TEAEs by severity were reported.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale
Mild TEAEs
5 Participants
5 Participants
5 Participants
5 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale
Moderate TEAEs
2 Participants
1 Participants
4 Participants
2 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale
Severe TEAEs
0 Participants
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 27

Population: The safety analysis set included all participants who were administered any dose of any study intervention.

Laboratory investigation included hematology, biochemistry and urinalysis. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in laboratory parameters were reported.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters
0 Participants
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 27

Population: The safety analysis set included all participants who were administered any dose of any study intervention.

Vital signs included body temperature, systolic and diastolic blood pressure and pulse rate. Clinical relevance was determined by the investigator. The number of participants with clinically relevant changes from baseline in vital signs were reported.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
0 Participants
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 27

Population: The safety analysis set included all participants who were administered any dose of any study intervention.

12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-Lead ECG findings were reported.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
0 Participants
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Cmax was obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ
S-(+)-PZQ
349 ng/mL
Geometric Coefficient of Variation 114.3
346 ng/mL
Geometric Coefficient of Variation 123.2
355 ng/mL
Geometric Coefficient of Variation 94.4
374 ng/mL
Geometric Coefficient of Variation 122.2
Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ
R-(-)-PZQ
67.8 ng/mL
Geometric Coefficient of Variation 148.3
71.4 ng/mL
Geometric Coefficient of Variation 138.8
66.2 ng/mL
Geometric Coefficient of Variation 132.9
80.0 ng/mL
Geometric Coefficient of Variation 176.2

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

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 (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
103 h*ng/mL
Geometric Coefficient of Variation 204.9
111 h*ng/mL
Geometric Coefficient of Variation 146.5
104 h*ng/mL
Geometric Coefficient of Variation 153.9
125 h*ng/mL
Geometric Coefficient of Variation 190.9
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
772 h*ng/mL
Geometric Coefficient of Variation 110.9
758 h*ng/mL
Geometric Coefficient of Variation 115.4
767 h*ng/mL
Geometric Coefficient of Variation 104.3
824 h*ng/mL
Geometric Coefficient of Variation 118.9

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for the specified category.

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was 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 (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
rac-PZQ
932 h*ng/mL
Geometric Coefficient of Variation 113.4
907 h*ng/mL
Geometric Coefficient of Variation 117.0
926 h*ng/mL
Geometric Coefficient of Variation 104.7
1001 h*ng/mL
Geometric Coefficient of Variation 123.8
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
175 h*ng/mL
Geometric Coefficient of Variation 115.1
166 h*ng/mL
Geometric Coefficient of Variation 97.9
157 h*ng/mL
Geometric Coefficient of Variation 94.9
179 h*ng/mL
Geometric Coefficient of Variation 145.7
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
813 h*ng/mL
Geometric Coefficient of Variation 111.6
792 h*ng/mL
Geometric Coefficient of Variation 114.0
808 h*ng/mL
Geometric Coefficient of Variation 103.7
864 h*ng/mL
Geometric Coefficient of Variation 118.7

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for the specified category.

Tmax was obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
rac-PZQ
2.50 hours
Interval 0.5 to 3.5
2.00 hours
Interval 0.5 to 4.0
2.50 hours
Interval 0.5 to 5.0
2.50 hours
Interval 0.5 to 4.5
Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
2.50 hours
Interval 0.5 to 3.5
2.00 hours
Interval 0.5 to 3.5
2.50 hours
Interval 0.5 to 5.0
2.50 hours
Interval 0.25 to 4.5
Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
2.50 hours
Interval 0.5 to 3.5
2.00 hours
Interval 0.5 to 4.0
2.50 hours
Interval 0.5 to 5.0
2.50 hours
Interval 0.5 to 4.5

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for the specified category.

Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLQ) before the occurrence of the first quantifiable concentration.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
rac-PZQ
0.750 hours
Interval 0.0 to 2.5
0.500 hours
Interval 0.0 to 2.5
1.00 hours
Interval 0.0 to 2.0
0.750 hours
Interval 0.0 to 2.5
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
1.00 hours
Interval 0.0 to 3.0
1.00 hours
Interval 0.0 to 3.0
1.00 hours
Interval 0.0 to 2.5
1.00 hours
Interval 0.0 to 2.57
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
0.750 hours
Interval 0.0 to 2.5
0.500 hours
Interval 0.0 to 2.5
1.00 hours
Interval 0.0 to 2.0
0.750 hours
Interval 0.0 to 2.5

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for the specified category.

Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
rac-PZQ
2.44 hours
Geometric Coefficient of Variation 4.00
2.08 hours
Geometric Coefficient of Variation 47.3
2.43 hours
Geometric Coefficient of Variation 47.9
2.20 hours
Geometric Coefficient of Variation 49.4
Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
1.39 hours
Geometric Coefficient of Variation 61.5
1.35 hours
Geometric Coefficient of Variation 48.8
1.35 hours
Geometric Coefficient of Variation 53.7
1.24 hours
Geometric Coefficient of Variation 54.4
Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
2.62 hours
Geometric Coefficient of Variation 43.6
2.18 hours
Geometric Coefficient of Variation 48.5
2.51 hours
Geometric Coefficient of Variation 47.2
2.34 hours
Geometric Coefficient of Variation 51.7

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for the specified category.

Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
rac-PZQ
0.284 1/hour
Geometric Coefficient of Variation 40.0
0.334 1/hour
Geometric Coefficient of Variation 47.3
0.285 1/hour
Geometric Coefficient of Variation 47.9
0.315 1/hour
Geometric Coefficient of Variation 49.4
Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
0.499 1/hour
Geometric Coefficient of Variation 61.5
0.514 1/hour
Geometric Coefficient of Variation 48.8
0.515 1/hour
Geometric Coefficient of Variation 53.7
0.559 1/hour
Geometric Coefficient of Variation 54.4
Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
0.265 1/hour
Geometric Coefficient of Variation 43.6
0.318 1/hour
Geometric Coefficient of Variation 48.5
0.276 1/hour
Geometric Coefficient of Variation 47.2
0.297 1/hour
Geometric Coefficient of Variation 51.7

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for the specified category.

CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
rac-PZQ
1287 liter per hour
Geometric Coefficient of Variation 113.4
1323 liter per hour
Geometric Coefficient of Variation 117.0
1296 liter per hour
Geometric Coefficient of Variation 104.7
1199 liter per hour
Geometric Coefficient of Variation 123.8
Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
6868 liter per hour
Geometric Coefficient of Variation 115.1
7251 liter per hour
Geometric Coefficient of Variation 97.9
7620 liter per hour
Geometric Coefficient of Variation 94.9
6700 liter per hour
Geometric Coefficient of Variation 145.7
Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
1475 liter per hour
Geometric Coefficient of Variation 111.6
1516 liter per hour
Geometric Coefficient of Variation 114.0
1486 liter per hour
Geometric Coefficient of Variation 103.7
1389 liter per hour
Geometric Coefficient of Variation 118.7

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12 hours post-dose in each treatment period

Population: The PK Analysis Set included all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signifies those participants who were evaluable for the specified category.

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf\*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.

Outcome measures

Outcome measures
Measure
Cesol First Administration
n=36 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=35 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 Participants
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
rac-PZQ
4528 liters
Geometric Coefficient of Variation 99.9
3963 liters
Geometric Coefficient of Variation 87.5
4542 liters
Geometric Coefficient of Variation 98.6
3801 liters
Geometric Coefficient of Variation 110.5
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
R-(-)-PZQ
13761 liters
Geometric Coefficient of Variation 70.3
14100 liters
Geometric Coefficient of Variation 63.4
14806 liters
Geometric Coefficient of Variation 56.8
11993 liters
Geometric Coefficient of Variation 83.7
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
S-(+)-PZQ
5568 liters
Geometric Coefficient of Variation 79.6
4765 liters
Geometric Coefficient of Variation 82.0
5385 liters
Geometric Coefficient of Variation 89.1
4685 liters
Geometric Coefficient of Variation 97.1

Adverse Events

Cesol First Administration

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Cesol Second Administration

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Biltricide First Administration

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Biltricide Second Administration

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Cesol First Administration
n=36 participants at risk
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 1) in either Treatment Period 1 or 2 under fed conditions.
Cesol Second Administration
n=34 participants at risk
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Cesol (Test 2) in either Treatment Period 3 or 4 under fed conditions.
Biltricide First Administration
n=36 participants at risk
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 1) in either Treatment Period 1 or 2 under fed conditions.
Biltricide Second Administration
n=34 participants at risk
Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 3 or 4 under fed conditions.
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Diarrhoea
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Dyspepsia
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.9%
1/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Flatulence
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Nausea
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.9%
1/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.9%
1/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Toothache
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Gastrointestinal disorders
Vomiting
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Nervous system disorders
Dizziness
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.9%
1/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Nervous system disorders
Dysgeusia
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Nervous system disorders
Headache
11.1%
4/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
8.8%
3/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
16.7%
6/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
14.7%
5/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Investigations
Body temperature increased
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.9%
1/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Investigations
C-reactive protein increased
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.9%
1/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.9%
1/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Skin and subcutaneous tissue disorders
Cold sweat
0.00%
0/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
2.8%
1/36 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.
0.00%
0/34 • Baseline up to Day 27
The Safety Analysis Set included all participants who were administered any dose of any study intervention.

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Results disclosure agreements

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