Bioequivalence Study of Coated Cesol Tablet Formulation Versus Biltricide

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04314037
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.4
• Patients Per Site Per Month: 25.5

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the bioequivalence (BE) of new coated Cesol tablet (Test) versus Biltricide tablets (Comparator) in healthy male participants. Praziquantel (rac-PZQ) is the active ingredient for Cesol and Biltricide tablets.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Cesol (Test); Drug: Biltricide (Reference)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase I, Open-label, Randomized, Four-period, Crossover, Fully Replicated, Reference-scaled, Single Center Study to Assess the Bioequivalence of a Single Oral Dose of 1200 mg of the Coated Cesol Tablet Formulation Versus Comparator Biltricide® in Healthy Male Volunteers
• Actual Study Start Date: Jun 17, 2020
• Actual Primary Completion Date: Jul 30, 2020
• Actual Study Completion Date: Jul 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence 1 (T1-R1-T2-R2) Participants will receive first dose of Cesol on Day 1 in treatment period 1 followed by first dose of Biltricide on Day 8 in treatment period 2 followed by second dose of Cesol on Day 15 in treatment period 3 followed by second dose of Biltricide on Day 22 in treatment period 4. A washout period of 7 days will be maintained between 4 treatment periods.	Drug: Cesol (Test); Participant will receive coated cesol tablet in sequence 1 (Day 1 and Day 15) and in sequence 2 (Day 8 and Day 22). A washout period of 7 days will be maintained between 4 treatment periods.; Other Names: Praziquantel ; Drug: Biltricide (Reference); Participant will receive biltricide tablet in Sequence 1 (Day 8 and Day 22) and in sequence 2 (Day 1 and Day 15). A washout period of 7 days will be maintained between 4 treatment periods.; Other Names: Praziquantel
Experimental: Sequence 2 (R1-T1-R2-T2) Participants will receive first dose of Biltricide on Day 1 in treatment period 1 followed by first dose of Cesol on Day 8 in treatment period 2 followed by second dose of Biltricide on Day 15 in treatment period 3 followed by second dose of Cesol on Day 22 in treatment period 4. A washout period of 7 days will be maintained between 4 treatment periods.	Drug: Cesol (Test); Participant will receive coated cesol tablet in sequence 1 (Day 1 and Day 15) and in sequence 2 (Day 8 and Day 22). A washout period of 7 days will be maintained between 4 treatment periods.; Other Names: Praziquantel ; Drug: Biltricide (Reference); Participant will receive biltricide tablet in Sequence 1 (Day 8 and Day 22) and in sequence 2 (Day 1 and Day 15). A washout period of 7 days will be maintained between 4 treatment periods.; Other Names: Praziquantel

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ) [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]

   Cmax was obtained directly from the concentration versus time curve.

2. Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemic-Praziquantel (Rac-PZQ) [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]

   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.

Secondary Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs [Baseline up to Day 27]

   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.

2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale [Baseline up to Day 27]

   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.

3. Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters [Baseline up to Day 27]

   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.

4. Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs [Baseline up to Day 27]

   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.

5. Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings [Baseline up to Day 27]

   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.

6. Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ [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]

   Cmax was obtained directly from the concentration versus time curve.

7. 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 [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]

   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.

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 [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]

   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.

9. Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ [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]

   Tmax was obtained directly from the concentration versus time curve.

10. Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ [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]

    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.

11. Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ [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]

    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.

12. Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ [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]

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

13. Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ [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]

    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.

14. Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ [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]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring

• Nonsmoker (=0 cigarettes, pipes, cigars or others) since at least 3 months

• Have a body weight within 55.0 to 95.0 kilogram (kg) and body mass index within the range of 18.5 to 29.9 kilogram per meter squared (kg/m^2)

• Electrocardiogram recording (12-lead) without signs of clinically relevant pathology in particular heart-rate corrected [QTc] (Bazett) <450 milliseconds (ms)

• Vital signs should be in normal range (systolic blood pressure: 90 to 140 millimeters of mercury [mmHg]; diastolic blood pressure: 50 to 90 mmHg; pulse rate: 50 to 90 beats per minute [bpm]; auricular body temperature between 35.9 degree centigrade [°C] to 37.6°C)

• Are males agreeing to refrain from donating sperm, Use a male condom when having sexual intercourse with a woman of child-bearing potential, who is not currently pregnant, and advise her to use a highly effective contraceptive method with a failure rate of less than (< )1 percent (%) per year

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Any condition, including any clinically relevant abnormality in the safety laboratory parameters as judged by the Investigator, that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation

• Have positive results from serology examination for Hepatitis B surface antigen (indicative of active Hepatitis B), Hepatitis C Virus or Human Immunodeficiency Virus (Human Immunodeficiency Virus 1/2 antibodies)

• Participants who have used drugs that may affect the pharmacokinetics of rac-PZQ from 15 days before dosing until the last PK sample, example., phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, oral ketoconazole

• Positive test for drugs of abuse (including alcohol) at Screening and prior to each dosing

• Unlikely to comply with the protocol requirements, instructions and study-related restrictions; example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study

• Participant is the Principal Investigator or any Sub investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study

• Inability to communicate or cooperate with the Investigator (example. language problem, illiterates, poor mental status) or to comply with the requirements of the entire study, including dietary restrictions

• Vulnerable participants (example., persons kept in detention).

• Legal incapacity or limited legal capacity

• Other protocol defined exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nuvisan GmbH	Neu-Ulm		Germany	89231

Sponsors and Collaborators

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

Investigators

• Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - Jan 9, 2020
• Statistical Analysis Plan - Jul 9, 2020

More Information

Additional Information:

• Trial Awareness and Transparency website

Publications

None provided.

• Responsible Party: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT04314037
• Other Study ID Numbers: MS200585_0004; 2019-002868-27
• First Posted: Mar 18, 2020
• Last Update Posted: Aug 13, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: Bioavailability; Bioequivalence; Praziquantel; Cesol; Pharmacokinetics
• Additional relevant MeSH terms: Praziquantel

Study Results

Participant Flow

Pre-assignment Detail	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).

Arm/Group Title	First Cesol, Then Biltricide, Then Cesol and Then Biltricide	First Biltricide, Then Cesol, Then Biltricide and Then Cesol
Arm/Group Description	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.	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.
Period Title: Treatment Period 1
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0
Period Title: Treatment Period 1
STARTED	18	18
COMPLETED	17	18
NOT COMPLETED	1	0
Period Title: Treatment Period 1
STARTED	17	18
COMPLETED	16	17
NOT COMPLETED	1	1
Period Title: Treatment Period 1
STARTED	16	17
COMPLETED	16	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	First Cesol, Then Biltricide, Then Cesol and Then Biltricide	First Biltricide, Then Cesol, Then Biltricide and Then Cesol	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	18	18	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32 (10.8)	37 (10.8)	34 (10.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	18 100%	18 100%	36 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	18 100%	18 100%	36 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 5.6%	1 2.8%
White	18 100%	17 94.4%	35 97.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ)
Description	Cmax was obtained directly from the concentration versus time curve.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	421 (118.3)	415 (129.1)	425 (98.3)	459 (129.5)

2. Primary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemic-Praziquantel (Rac-PZQ)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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
Measure Participants	36	34	35	34
Geometric Mean (Geometric Coefficient of Variation) [hours*nanogram per milliliter (h*ng/mL)]	894 (114.6)	873 (118.9)	886 (105.7)	964 (124.8)

3. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
Description	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.
Time Frame	Baseline up to Day 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	36	34
TEAEs	6 33.3%	6 33.3%	7 19.4%	7 NaN
Treatment related TEAEs	6 33.3%	6 33.3%	7 19.4%	6 NaN

4. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale
Description	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.
Time Frame	Baseline up to Day 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	36	34
Mild TEAEs	5 27.8%	5 27.8%	5 13.9%	5 NaN
Moderate TEAEs	2 11.1%	1 5.6%	4 11.1%	2 NaN
Severe TEAEs	0 0%	0 0%	0 0%	0 NaN

5. Secondary Outcome

Title	Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters
Description	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.
Time Frame	Baseline up to Day 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	36	34
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

6. Secondary Outcome

Title	Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
Description	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.
Time Frame	Baseline up to Day 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	Participants who received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference 2) in either Treatment Period 1 or 2 under fed conditions.
Measure Participants	36	34	36	34
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

7. Secondary Outcome

Title	Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
Description	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.
Time Frame	Baseline up to Day 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	36	34
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

8. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ
Description	Cmax was obtained directly from the concentration versus time curve.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
R-(-)-PZQ	67.8 (148.3)	71.4 (138.8)	66.2 (132.9)	80.0 (176.2)
S-(+)-PZQ	349 (114.3)	346 (123.2)	355 (94.4)	374 (122.2)

9. Secondary Outcome

Title	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
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
R-(-)-PZQ	103 (204.9)	111 (146.5)	104 (153.9)	125 (190.9)
S-(+)-PZQ	772 (110.9)	758 (115.4)	767 (104.3)	824 (118.9)

10. Secondary Outcome

Title	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
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
rac-PZQ	932 (113.4)	907 (117.0)	926 (104.7)	1001 (123.8)
R-(-)-PZQ	175 (115.1)	166 (97.9)	157 (94.9)	179 (145.7)
S-(+)-PZQ	813 (111.6)	792 (114.0)	808 (103.7)	864 (118.7)

11. Secondary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
Description	Tmax was obtained directly from the concentration versus time curve.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
rac-PZQ	2.50	2.00	2.50	2.50
R-(-)-PZQ	2.50	2.00	2.50	2.50
S-(+)-PZQ	2.50	2.00	2.50	2.50

12. Secondary Outcome

Title	Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
rac-PZQ	0.750	0.500	1.00	0.750
R-(-)-PZQ	1.00	1.00	1.00	1.00
S-(+)-PZQ	0.750	0.500	1.00	0.750

13. Secondary Outcome

Title	Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
rac-PZQ	2.44 (4.00)	2.08 (47.3)	2.43 (47.9)	2.20 (49.4)
R-(-)-PZQ	1.39 (61.5)	1.35 (48.8)	1.35 (53.7)	1.24 (54.4)
S-(+)-PZQ	2.62 (43.6)	2.18 (48.5)	2.51 (47.2)	2.34 (51.7)

14. Secondary Outcome

Title	Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
Description	Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
rac-PZQ	0.284 (40.0)	0.334 (47.3)	0.285 (47.9)	0.315 (49.4)
R-(-)-PZQ	0.499 (61.5)	0.514 (48.8)	0.515 (53.7)	0.559 (54.4)
S-(+)-PZQ	0.265 (43.6)	0.318 (48.5)	0.276 (47.2)	0.297 (51.7)

15. Secondary Outcome

Title	Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
rac-PZQ	1287 (113.4)	1323 (117.0)	1296 (104.7)	1199 (123.8)
R-(-)-PZQ	6868 (115.1)	7251 (97.9)	7620 (94.9)	6700 (145.7)
S-(+)-PZQ	1475 (111.6)	1516 (114.0)	1486 (103.7)	1389 (118.7)

16. Secondary Outcome

Title	Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cesol First Administration	Cesol Second Administration	Biltricide First Administration	Biltricide Second Administration
Arm/Group Description	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.	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.	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.	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.
Measure Participants	36	34	35	34
rac-PZQ	4528 (99.9)	3963 (87.5)	4542 (98.6)	3801 (110.5)
R-(-)-PZQ	13761 (70.3)	14100 (63.4)	14806 (56.8)	11993 (83.7)
S-(+)-PZQ	5568 (79.6)	4765 (82.0)	5385 (89.1)	4685 (97.1)

Adverse Events

Time Frame	Baseline up to Day 27
Adverse Event Reporting Description	The Safety Analysis Set included all participants who were administered any dose of any study intervention.
Arm/Group Title	Cesol First Administration		Cesol Second Administration		Biltricide First Administration		Biltricide Second Administration
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Cesol First Administration		Cesol Second Administration		Biltricide First Administration		Biltricide Second Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/34 (0%)		0/36 (0%)		0/34 (0%)
Serious Adverse Events
	Cesol First Administration		Cesol Second Administration		Biltricide First Administration		Biltricide Second Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/34 (0%)		0/36 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Cesol First Administration		Cesol Second Administration		Biltricide First Administration		Biltricide Second Administration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/36 (16.7%)		6/34 (17.6%)		7/36 (19.4%)		7/34 (20.6%)
Gastrointestinal disorders
Abdominal pain upper	0/36 (0%)		0/34 (0%)		1/36 (2.8%)		0/34 (0%)
Diarrhoea	1/36 (2.8%)		0/34 (0%)		1/36 (2.8%)		0/34 (0%)
Dyspepsia	0/36 (0%)		1/34 (2.9%)		0/36 (0%)		0/34 (0%)
Flatulence	1/36 (2.8%)		0/34 (0%)		0/36 (0%)		0/34 (0%)
Nausea	1/36 (2.8%)		1/34 (2.9%)		1/36 (2.8%)		1/34 (2.9%)
Toothache	1/36 (2.8%)		0/34 (0%)		0/36 (0%)		0/34 (0%)
Vomiting	1/36 (2.8%)		0/34 (0%)		1/36 (2.8%)		0/34 (0%)
Investigations
Body temperature increased	0/36 (0%)		0/34 (0%)		0/36 (0%)		1/34 (2.9%)
C-reactive protein increased	0/36 (0%)		0/34 (0%)		0/36 (0%)		1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Back pain	0/36 (0%)		0/34 (0%)		0/36 (0%)		1/34 (2.9%)
Nervous system disorders
Dizziness	0/36 (0%)		1/34 (2.9%)		0/36 (0%)		0/34 (0%)
Dysgeusia	1/36 (2.8%)		0/34 (0%)		0/36 (0%)		0/34 (0%)
Headache	4/36 (11.1%)		3/34 (8.8%)		6/36 (16.7%)		5/34 (14.7%)
Skin and subcutaneous tissue disorders
Cold sweat	0/36 (0%)		0/34 (0%)		1/36 (2.8%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.