Healthy
Conditions
Keywords
Bioavailability, Bioequivalence, Praziquantel, Cysticide, Pharmacokinetics
Brief summary
The purpose of this trial is to assess the bioequivalence (BE) of new 600 milligram (mg) Cisticid tablet (Test) versus 600 mg Biltricide tablets (Reference) at a dose of 1200 mg in healthy male participants. Praziquantel (PZQ) is the active ingredient for Cisticid and Biltricide tablets.
Interventions
DRUGCisticid
Participants received single oral dose of 1200 mg (two 600 mg tablets) Cisticid (Test) on Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2) or Day 15 (Treatment Period 3).
DRUGBiltricide
Participants received 600 mg of Biltricide (Reference) tablet at a dose of 1200 mg on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Sponsors
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
* A male participant must agree to use and to have their female partners willing to use additional non-hormonal contraception (for example, condoms or occlusive cap with spermicide, non-hormonal intra-uterine device \[IUD\], previous sterilization of participant or his partner, being sexually inactive) from Day of randomization up to final end of treatment (EOT) visit * Gave written informed consent prior to any trial related procedure * Have a body weight (BW) of greater than (\>) 55.0 kilogram (kg) to less than (\<) 95 kg and a body mass index (BMI) between 18.0 and 27.0 kg/meter square (m\^2) * Able to communicate well with the Investigator, understanding the protocol requirements and restrictions, and willing to comply with the requirements of the entire trial * Non-smoker (= 0 cigarettes, pipes, cigars or others) since at least three months * 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: 45 to 90 beats per minute \[bpm\]; oral body temperature between 35.0 degree centigrade \[°C\] to 37.5°C) * All values for biochemistry, liver function test and hematology tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the Investigator. Hematocrit and hemoglobin must be above the lower limit; upper limit may range up to 15 percent (%). Remaining results, including white blood cells may range +/- 15%, if participant is asymptomatic * Negative screen for alcohol and drugs of abuse (opiate class, barbiturates, cocaine and metabolites, amphetamines, cannabinoids, benzodiazepines and tricyclic antidepressants) at screening and on each admission * Negative screen for Hepatitis B surface (HBs) antigens, Hepatitis C Virus (HCV) antibodies, Hepatitis A Virus (HAV) antibodies and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Any surgical or medical condition, including findings in the medical history or in the pre-study assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the participant in the study or that could interfere with the study objectives, conduct or evaluation * History of surgery of the gastrointestinal (GI) tract, history of other GI tract diseases, or acute GI tract infections in the last 2 weeks, which could influence the gastrointestinal absorption and/or motility according to the Investigator's opinion * Any clinically relevant abnormality in the safety laboratory parameters as judged by the Investigator * Have positive results from serology examination for Hepatitis B surface (HBs) antigen, Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) * Allergy: ascertained or presumptive hypersensitivity to the active drug substance and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the trial * History or presence of drug abuse (opiate class, barbiturates, cocaine and its main metabolite, amphetamines, cannabinoids, benzodiazepines and tricyclic antidepressants) or alcohol abuse at screening and on each admission. Alcohol abuse is defined by the assessment of the Investigator * Loss or donation of more than 400 milliliter (mL) of blood within 90 days prior to first Praziquantel (PZQ) administration * Administration of any investigational product or use of any investigational device in any clinical study within 30 days prior to first PZQ administration. Participants who have used drugs that may affect the pharmacokinetics of PZQ from 14 days before dosing until the last pharmacokinetic (PK) sample, for example, phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, oral ketoconazole * Consumption of substances known to be potent inhibitors or inducers of Cytochrome P450s (CYP P450s) such as grapefruit, orange, cranberry or juices of these fruits, herbal remedies or dietary supplements containing St. John's Wort, poppy seeds, cruciferic vegetables, in the two weeks before dosing until last PK sample * Unlikely to comply with the protocol requirements, instructions and trial-related restrictions, for example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial * Non-acceptance or non-compliance with the study breakfast (for example, vegetarians, vegans and participants who follow special diets) * Excessive consumption of beverages containing xanthine (\>5 cups of coffee a day or equivalent) or inability to stop consuming caffeine from 48 hours prior to drug administration until discharge from the clinic * Participant is the Investigator or any Sub-Investigator, research assistant, pharmacist, trial coordinator, other staff or relative thereof directly involved in the conduct of the trial * Vulnerable participants (for example, persons kept in detention) * Legal incapacity or limited legal capacity * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-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 12.0 hours post-dose | Area under the plasma concentration-time curve from 0 to the time of the last quantifiable concentration. |
| Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-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 12.0 hours post-dose | The maximum observed plasma concentration of L-Praziquantel (L-PZQ). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | AUC0-inf is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). |
| Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | AUCextra was reported in terms of percentage of AUC0-inf. |
| Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | 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. |
| Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | Lambda Z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. |
| Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd/f after oral dose was influenced by the fraction absorbed. |
| Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | Time of the maximum drug concentration. |
| Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (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 12.0 hours post-dose | The maximum observed plasma concentration of rac-Praziquantel (rac-PZQ). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to Day 29 | An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | Baseline up to Day 29 | Number of participants with clinically significant abnormalities in laboratory parameters were reported. Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Baseline up to Day 29 | Number of participants with clinically significant abnormalities in vital signs were reported. Vital signs included body temperature, systolic / diastolic blood pressure, and pulse rate. |
| Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | Baseline up to Day 29 | Number of participants with clinically significant abnormalities in 12-lead electrocardiogram (ECG) were reported. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (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 12.0 hours post-dose | Area under the drug plasma concentration-time curve from time zero to the time last measurable concentration. |
| Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (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 12.0 hours post-dose | Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| First Cisticid, Then Biltricide, Then Biltricide Participants received single oral dose of 1200 milligrams (mg) (two 600 mg tablets) Cisticid (Test) on Day 1 in Treatment Period 1 followed by single oral dose of 1200 mg (two 600 mg tablets) of Biltricide (Reference) on Day 8 in Treatment Period 2 and on Day 15 in Treatment Period 3. A washout period will be maintained between 3 treatment periods. | 20 |
| First Biltricide, Then Cisticid, Then Biltricide Participants received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference) on Day 1 in Treatment Period 1 followed by single oral dose of 1200 mg (two 600 mg tablets) of Cisticid (Test) on Day 8 in Treatment Period 2 and then single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference) on Day 15 in Treatment Period 3. A washout period will be maintained between 3 treatment periods. | 20 |
| First Biltricide, Then Biltricide, Then Cisticid Participants received single oral dose of 1200 mg (two 600 mg tablets) Biltricide (Reference) on Day 1 in Treatment Period 1 and on Day 8 in Treatment Period 2 followed by single oral dose of 1200 mg (two 600 mg tablets) of Cisticid (Test) on Day 15 in Treatment Period 3. A washout period will be maintained between 3 treatment periods. | 20 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Period 1 | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | First Cisticid, Then Biltricide, Then Biltricide | First Biltricide, Then Cisticid, Then Biltricide | First Biltricide, Then Biltricide, Then Cisticid | Total |
|---|---|---|---|---|
| Age, Continuous | 27.80 Years STANDARD_DEVIATION 7.83 | 28.65 Years STANDARD_DEVIATION 7.46 | 27.20 Years STANDARD_DEVIATION 5.31 | 27.88 Years STANDARD_DEVIATION 6.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 60 | 0 / 60 |
| other Total, other adverse events | 2 / 60 | 5 / 60 | 6 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 | 0 / 60 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ)
Area under the plasma concentration-time curve from 0 to the time of the last 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 12.0 hours post-dose
Population: Pharmacokinetic (PK) analysis set included all participants who received all administrations of treatment and have PK parameters for AUC0-t and maximum observed plasma concentration (Cmax) in all periods and without any relevant protocol violations and factors likely to affect the comparability of PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cisticid | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ) | 441.53 Hour*nanogram per milliliter (h*ng/ml) | Standard Deviation 345.7 |
| Biltricide First Administration | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ) | 547.41 Hour*nanogram per milliliter (h*ng/ml) | Standard Deviation 384.82 |
| Biltricide Second Administration | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ) | 460.25 Hour*nanogram per milliliter (h*ng/ml) | Standard Deviation 343.37 |
Primary
Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ)
The maximum observed plasma concentration of L-Praziquantel (L-PZQ).
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 12.0 hours post-dose
Population: PK analysis set included all participant who received all administrations of treatment and have PK parameters for AUC0-t and Cmax in all periods and without any relevant protocol violations and factors likely to affect the comparability of PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cisticid | Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ) | 310.87 ng/mL | Standard Deviation 249.02 |
| Biltricide First Administration | Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ) | 426.42 ng/mL | Standard Deviation 324.01 |
| Biltricide Second Administration | Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ) | 363.20 ng/mL | Standard Deviation 333.5 |
Secondary
Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
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 12.0 hours post-dose
Population: PK analysis set: All participants who received all administrations of treatment \& have PK parameters for AUC0-t \& Cmax in all periods without any relevant protocol violations \& factors likely to affect comparability of PK results. Here Number analyzed signifies those participants who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cisticid | Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 749261.50 Milliliter per hour | Standard Deviation 744206.88 |
| Cisticid | Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 147268.6 Milliliter per hour | Standard Deviation 122977.13 |
| Biltricide First Administration | Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 585260.42 Milliliter per hour | Standard Deviation 541013.95 |
| Biltricide First Administration | Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 128110.14 Milliliter per hour | Standard Deviation 122864.03 |
| Biltricide Second Administration | Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 673193.51 Milliliter per hour | Standard Deviation 531848.19 |
| Biltricide Second Administration | Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 155851.99 Milliliter per hour | Standard Deviation 145104.37 |
Secondary
Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd/f after oral dose was influenced by the fraction absorbed.
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 12.0 hours post-dose
Population: PK analysis set: All participants who received all administrations of treatment \& have PK parameters for AUC0-t \& Cmax in all periods without any relevant protocol violations \& factors likely to affect comparability of PK results. Here Number analyzed signifies those participants who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cisticid | Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 1540237.10 Milliliter | Standard Deviation 1069504.21 |
| Cisticid | Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 430368.23 Milliliter | Standard Deviation 328721.73 |
| Biltricide First Administration | Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 1660474.33 Milliliter | Standard Deviation 1619772.26 |
| Biltricide First Administration | Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 385223.26 Milliliter | Standard Deviation 279076.69 |
| Biltricide Second Administration | Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 1800582.47 Milliliter | Standard Deviation 1385707.17 |
| Biltricide Second Administration | Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 431494.33 Milliliter | Standard Deviation 350782.53 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
AUC0-inf is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
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 12.0 hours post-dose
Population: PK analysis set: All participants who received all administrations of treatment \& have PK parameters for AUC0-t \& Cmax in all periods without any relevant protocol violations \& factors likely to affect comparability of PK results. Here Number analyzed signifies those participants who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cisticid | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 468.52 h*ng/ml | Standard Deviation 352.29 |
| Cisticid | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2130.19 h*ng/ml | Standard Deviation 1417.81 |
| Biltricide First Administration | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 584.23 h*ng/ml | Standard Deviation 410.05 |
| Biltricide First Administration | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2509.42 h*ng/ml | Standard Deviation 1624.33 |
| Biltricide Second Administration | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 497.89 h*ng/ml | Standard Deviation 348.81 |
| Biltricide Second Administration | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2189.25 h*ng/ml | Standard Deviation 1403.14 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ)
Area under the drug plasma concentration-time curve from time zero to the time last measurable 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 12.0 hours post-dose
Population: PK analysis set included all participant who received all administrations of treatment and have PK parameters for AUC0-t and Cmax in all periods and without any relevant protocol violations and factors likely to affect the comparability of PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cisticid | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ) | 2071.35 h*ng/ml | Standard Deviation 1370.58 |
| Biltricide First Administration | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ) | 2421.73 h*ng/ml | Standard Deviation 1518.94 |
| Biltricide Second Administration | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ) | 2131.01 h*ng/ml | Standard Deviation 1353.64 |
Secondary
Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
AUCextra was reported in terms of percentage of AUC0-inf.
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 12.0 hours post-dose
Population: PK analysis set: All participants who received all administrations of treatment \& have PK parameters for AUC0-t \& Cmax in all periods without any relevant protocol violations \& factors likely to affect comparability of PK results. Here Number analyzed signifies those participants who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cisticid | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 5.36 Percentage of AUC0-inf | Standard Deviation 3.73 |
| Cisticid | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.60 Percentage of AUC0-inf | Standard Deviation 1.73 |
| Biltricide First Administration | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 5.49 Percentage of AUC0-inf | Standard Deviation 6.47 |
| Biltricide First Administration | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.84 Percentage of AUC0-inf | Standard Deviation 2.56 |
| Biltricide Second Administration | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 5.74 Percentage of AUC0-inf | Standard Deviation 4.02 |
| Biltricide Second Administration | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.57 Percentage of AUC0-inf | Standard Deviation 1.56 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ)
The maximum observed plasma concentration of rac-Praziquantel (rac-PZQ).
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 12.0 hours post-dose
Population: PK analysis set included all participant who received all administrations of treatment and have PK parameters for AUC0-t and Cmax in all periods and without any relevant protocol violations and factors likely to affect the comparability of PK results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cisticid | Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ) | 1209.15 ng/mL | Standard Deviation 803.2 |
| Biltricide First Administration | Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ) | 1530.23 ng/mL | Standard Deviation 944.12 |
| Biltricide Second Administration | Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ) | 1356.18 ng/mL | Standard Deviation 1011.46 |
Secondary
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
Number of participants with clinically significant abnormalities in 12-lead electrocardiogram (ECG) were reported. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position.
Time frame: Baseline up to Day 29
Population: Safety Analysis Set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cisticid | Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Biltricide First Administration | Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
| Biltricide Second Administration | Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Number of participants with clinically significant abnormalities in laboratory parameters were reported. Laboratory investigation included hematology, biochemistry, urinalysis and coagulation.
Time frame: Baseline up to Day 29
Population: Safety Analysis Set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cisticid | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | 0 Participants |
| Biltricide First Administration | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | 0 Participants |
| Biltricide Second Administration | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Number of participants with clinically significant abnormalities in vital signs were reported. Vital signs included body temperature, systolic / diastolic blood pressure, and pulse rate.
Time frame: Baseline up to Day 29
Population: Safety Analysis Set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cisticid | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Biltricide First Administration | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| Biltricide Second Administration | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time frame: Baseline up to Day 29
Population: Safety Analysis Set included all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cisticid | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 2 Participants |
| Cisticid | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Biltricide First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 5 Participants |
| Biltricide First Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Biltricide Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 6 Participants |
| Biltricide Second Administration | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
Secondary
Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-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.
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 12.0 hours post-dose
Population: PK analysis set: All participants who received all administrations of treatment \& have PK parameters for AUC0-t \& Cmax in all periods without any relevant protocol violations \& factors likely to affect comparability of PK results. Here Number analyzed signifies those participants who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cisticid | Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 1.87 hours | Standard Deviation 1.12 |
| Cisticid | Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.19 hours | Standard Deviation 0.91 |
| Biltricide First Administration | Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 2.59 hours | Standard Deviation 3.01 |
| Biltricide First Administration | Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.54 hours | Standard Deviation 1.73 |
| Biltricide Second Administration | Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 2.32 hours | Standard Deviation 1.65 |
| Biltricide Second Administration | Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.18 hours | Standard Deviation 0.9 |
Secondary
Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-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 12.0 hours post-dose
Population: PK analysis set included all participants who received all administrations of treatment and have PK parameters for AUC0-t and Cmax in all periods and without any relevant protocol violations and factors likely to affect the comparability of PK results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cisticid | Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 0.452927 Per hour |
| Cisticid | Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 0.365639 Per hour |
| Biltricide First Administration | Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 0.383267 Per hour |
| Biltricide First Administration | Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 0.331359 Per hour |
| Biltricide Second Administration | Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 0.370854 Per hour |
| Biltricide Second Administration | Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 0.370806 Per hour |
Secondary
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-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 (LLOQ) 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 12.0 hours post-dose
Population: PK analysis set included all participant who received all administrations of treatment and have PK parameters for AUC0-t and Cmax in all periods and without any relevant protocol violations and factors likely to affect the comparability of PK results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cisticid | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 1 hours |
| Cisticid | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 0.75 hours |
| Biltricide First Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 1 hours |
| Biltricide First Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 0.75 hours |
| Biltricide Second Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 1 hours |
| Biltricide Second Administration | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 0.75 hours |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Time of the maximum drug 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 12.0 hours post-dose
Population: PK analysis set included all participant who received all administrations of treatment and have PK parameters for AUC0-t and Cmax in all periods and without any relevant protocol violations and factors likely to affect the comparability of PK results.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cisticid | Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 2.5 hours |
| Cisticid | Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.5 hours |
| Biltricide First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 2 hours |
| Biltricide First Administration | Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2 hours |
| Biltricide Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | L-PZQ | 2.5 hours |
| Biltricide Second Administration | Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ) | Rac-PZQ | 2.5 hours |