Healthy
Conditions
Keywords
Bioavailability, Bioequivalence, Praziquantel, Cesol, Pharmacokinetics
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.
Interventions
DRUGCesol (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.
DRUGBiltricide (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.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Germany
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 18 |
| 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. | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 2 | Adverse Event | 1 | 0 |
| Treatment Period 3 | Adverse Event | 0 | 1 |
| Treatment Period 3 | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | First Biltricide, Then Cesol, Then Biltricide and Then Cesol | Total | First Cesol, Then Biltricide, Then Cesol and Then Biltricide |
|---|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 10.8 | 34 years STANDARD_DEVIATION 10.8 | 32 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 36 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 35 Participants | 18 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 18 Participants | 36 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 34 | 0 / 36 | 0 / 34 |
| other Total, other adverse events | 6 / 36 | 6 / 34 | 7 / 36 | 7 / 34 |
| serious Total, serious adverse events | 0 / 36 | 0 / 34 | 0 / 36 | 0 / 34 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemic-Praziquantel (Rac-PZQ)
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol Second Administration | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemic-Praziquantel (Rac-PZQ) | 873 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 118.9 |
| Biltricide First Administration | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemic-Praziquantel (Rac-PZQ) | 886 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 105.7 |
| Biltricide Second Administration | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemic-Praziquantel (Rac-PZQ) | 964 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 124.8 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ)
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
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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cesol First Administration | Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ) | 421 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 118.3 |
| Cesol Second Administration | Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ) | 415 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 129.1 |
| Biltricide First Administration | Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ) | 425 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 98.3 |
| Biltricide Second Administration | Maximum Observed Plasma Concentration (Cmax) of Racemic-Praziquantel (Rac-PZQ) | 459 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 129.5 |
Secondary
Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 1516 liter per hour | Geometric Coefficient of Variation 114 |
| Cesol Second Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 1323 liter per hour | Geometric Coefficient of Variation 117 |
| Cesol Second Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 7251 liter per hour | Geometric Coefficient of Variation 97.9 |
| Biltricide First Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 7620 liter per hour | Geometric Coefficient of Variation 94.9 |
| Biltricide First Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 1486 liter per hour | Geometric Coefficient of Variation 103.7 |
| Biltricide First Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 1296 liter per hour | Geometric Coefficient of Variation 104.7 |
| Biltricide Second Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 1199 liter per hour | Geometric Coefficient of Variation 123.8 |
| Biltricide Second Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 1389 liter per hour | Geometric Coefficient of Variation 118.7 |
| Biltricide Second Administration | Apparent Clearance (CL/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 6700 liter per hour | Geometric Coefficient of Variation 145.7 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 4765 liters | Geometric Coefficient of Variation 82 |
| Cesol Second Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 14100 liters | Geometric Coefficient of Variation 63.4 |
| Cesol Second Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 3963 liters | Geometric Coefficient of Variation 87.5 |
| Biltricide First Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 4542 liters | Geometric Coefficient of Variation 98.6 |
| Biltricide First Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 5385 liters | Geometric Coefficient of Variation 89.1 |
| Biltricide First Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 14806 liters | Geometric Coefficient of Variation 56.8 |
| Biltricide Second Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 4685 liters | Geometric Coefficient of Variation 97.1 |
| Biltricide Second Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 3801 liters | Geometric Coefficient of Variation 110.5 |
| Biltricide Second Administration | Apparent Volume of Distribution During Terminal Phase (Vz/f) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 11993 liters | Geometric Coefficient of Variation 83.7 |
Secondary
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
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | 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 | 907 h*ng/mL | Geometric Coefficient of Variation 117 |
| Cesol Second Administration | 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 | 166 h*ng/mL | Geometric Coefficient of Variation 97.9 |
| Cesol Second Administration | 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 | 792 h*ng/mL | Geometric Coefficient of Variation 114 |
| Biltricide First Administration | 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 | 926 h*ng/mL | Geometric Coefficient of Variation 104.7 |
| Biltricide First Administration | 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 | 157 h*ng/mL | Geometric Coefficient of Variation 94.9 |
| Biltricide First Administration | 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 | 808 h*ng/mL | Geometric Coefficient of Variation 103.7 |
| Biltricide Second Administration | 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 | 179 h*ng/mL | Geometric Coefficient of Variation 145.7 |
| Biltricide Second Administration | 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 | 864 h*ng/mL | Geometric Coefficient of Variation 118.7 |
| Biltricide Second Administration | 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 | 1001 h*ng/mL | Geometric Coefficient of Variation 123.8 |
Secondary
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
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | 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 | 758 h*ng/mL | Geometric Coefficient of Variation 115.4 |
| Cesol Second Administration | 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 | 111 h*ng/mL | Geometric Coefficient of Variation 146.5 |
| Biltricide First Administration | 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 | 104 h*ng/mL | Geometric Coefficient of Variation 153.9 |
| Biltricide First Administration | 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 | 767 h*ng/mL | Geometric Coefficient of Variation 104.3 |
| Biltricide Second Administration | 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 | 125 h*ng/mL | Geometric Coefficient of Variation 190.9 |
| Biltricide Second Administration | 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 | 824 h*ng/mL | Geometric Coefficient of Variation 118.9 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ | S-(+)-PZQ | 346 ng/mL | Geometric Coefficient of Variation 123.2 |
| Cesol Second Administration | Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ | R-(-)-PZQ | 71.4 ng/mL | Geometric Coefficient of Variation 138.8 |
| Biltricide First Administration | Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ | S-(+)-PZQ | 355 ng/mL | Geometric Coefficient of Variation 94.4 |
| Biltricide First Administration | Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ | R-(-)-PZQ | 66.2 ng/mL | Geometric Coefficient of Variation 132.9 |
| Biltricide Second Administration | Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ | R-(-)-PZQ | 80.0 ng/mL | Geometric Coefficient of Variation 176.2 |
| Biltricide Second Administration | Maximum Observed Plasma Concentration (Cmax) of Praziquantel (PZQ) Enantiomers: R-(-)-PZQ and S-(+) PZQ | S-(+)-PZQ | 374 ng/mL | Geometric Coefficient of Variation 122.2 |
Secondary
Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters
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
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cesol First Administration | Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters | 0 Participants |
| Cesol Second Administration | Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters | 0 Participants |
| Biltricide First Administration | Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters | 0 Participants |
| Biltricide Second Administration | Number of Participants With Clinically Relevant Changes From Baseline in Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
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
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cesol First Administration | Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs | 0 Participants |
| Cesol Second Administration | Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs | 0 Participants |
| Biltricide First Administration | Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs | 0 Participants |
| Biltricide Second Administration | Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
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
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cesol First Administration | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Cesol Second Administration | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Biltricide First Administration | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
| Biltricide Second Administration | Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
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
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cesol First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | TEAEs | 6 Participants |
| Cesol First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | Treatment related TEAEs | 6 Participants |
| Cesol Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | Treatment related TEAEs | 6 Participants |
| Cesol Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | TEAEs | 6 Participants |
| Biltricide First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | TEAEs | 7 Participants |
| Biltricide First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | Treatment related TEAEs | 7 Participants |
| Biltricide Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | TEAEs | 7 Participants |
| Biltricide Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs | Treatment related TEAEs | 6 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale
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
Population: The safety analysis set included all participants who were administered any dose of any study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cesol First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Moderate TEAEs | 2 Participants |
| Cesol First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Severe TEAEs | 0 Participants |
| Cesol First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Mild TEAEs | 5 Participants |
| Cesol Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Moderate TEAEs | 1 Participants |
| Cesol Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Severe TEAEs | 0 Participants |
| Cesol Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Mild TEAEs | 5 Participants |
| Biltricide First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Mild TEAEs | 5 Participants |
| Biltricide First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Moderate TEAEs | 4 Participants |
| Biltricide First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Severe TEAEs | 0 Participants |
| Biltricide Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Severe TEAEs | 0 Participants |
| Biltricide Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Mild TEAEs | 5 Participants |
| Biltricide Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity According to Qualitative Toxicity Scale | Moderate TEAEs | 2 Participants |
Secondary
Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 2.08 hours | Geometric Coefficient of Variation 47.3 |
| Cesol Second Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 2.18 hours | Geometric Coefficient of Variation 48.5 |
| Cesol Second Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 1.35 hours | Geometric Coefficient of Variation 48.8 |
| Biltricide First Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 2.43 hours | Geometric Coefficient of Variation 47.9 |
| Biltricide First Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 1.35 hours | Geometric Coefficient of Variation 53.7 |
| Biltricide First Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 2.51 hours | Geometric Coefficient of Variation 47.2 |
| Biltricide Second Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 2.34 hours | Geometric Coefficient of Variation 51.7 |
| Biltricide Second Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 1.24 hours | Geometric Coefficient of Variation 54.4 |
| Biltricide Second Administration | Terminal Elimination Half-Life (T1/2) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 2.20 hours | Geometric Coefficient of Variation 49.4 |
Secondary
Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 0.318 1/hour | Geometric Coefficient of Variation 48.5 |
| Cesol Second Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 0.514 1/hour | Geometric Coefficient of Variation 48.8 |
| Cesol Second Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 0.334 1/hour | Geometric Coefficient of Variation 47.3 |
| Biltricide First Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 0.276 1/hour | Geometric Coefficient of Variation 47.2 |
| Biltricide First Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 0.285 1/hour | Geometric Coefficient of Variation 47.9 |
| Biltricide First Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 0.515 1/hour | Geometric Coefficient of Variation 53.7 |
| Biltricide Second Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 0.559 1/hour | Geometric Coefficient of Variation 54.4 |
| Biltricide Second Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 0.315 1/hour | Geometric Coefficient of Variation 49.4 |
| Biltricide Second Administration | Terminal Rate Constant (Lambda z) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 0.297 1/hour | Geometric Coefficient of Variation 51.7 |
Secondary
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
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
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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol First Administration | 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 |
| Cesol Second Administration | 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 |
| Cesol Second Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 0.500 hours |
| Cesol Second Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 0.500 hours |
| Biltricide First Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 1.00 hours |
| Biltricide First Administration | 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 |
| Biltricide First Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 1.00 hours |
| Biltricide Second Administration | 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 |
| Biltricide Second Administration | 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 |
| Biltricide Second Administration | 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 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ
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
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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cesol First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 2.50 hours |
| Cesol First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 2.50 hours |
| Cesol First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 2.50 hours |
| Cesol Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 2.00 hours |
| Cesol Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 2.00 hours |
| Cesol Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 2.00 hours |
| Biltricide First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 2.50 hours |
| Biltricide First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 2.50 hours |
| Biltricide First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 2.50 hours |
| Biltricide Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | rac-PZQ | 2.50 hours |
| Biltricide Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | S-(+)-PZQ | 2.50 hours |
| Biltricide Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of Racemic-Praziquantel (Rac-PZQ), R-(-)-PZQ and S-(+)-PZQ | R-(-)-PZQ | 2.50 hours |