Healthy
Conditions
Keywords
ODT-PZQ, Bio-availability, Praziquantel, Cysticide, Pharmacokinetics
Brief summary
This is a phase I, open-label, randomized, 4 period, crossover, single-center trial. The purpose of this trial is to assess the relative bio-availability of racemate Oral Dispersible Tablet praziquantel (ODT-PQZ) (MSC1028703A) 150 milligram (mg) versus the current marketed praziquantel (PZQ) (Cysticide® 500 mg) formulation in healthy male volunteers.
Interventions
DRUGOral dispersible tablet of praziquantel (ODT-PZQ)
Treatment A (test): ODT-PZQ (MSC1028703A) at a single dose of 40 milligram per kilogram (mg/kg) orally dispersed in water after meal.
DRUGCysticide
Treatment B (reference): Cysticide tablet at a single dose of 40 mg/kg will be given with water orally after a meal.
DRUGODT-PZQ
Treatment C1 (test): ODT-PZQ (MSC1028703A) at a single dose of 20 mg/kg orally dispersed in water after a meal.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males 18-55 years of age (inclusive at screening) * Male subjects with partners of childbearing potential must have had a vasectomy or use acceptable methods of birth control (that is, condoms) and not donate sperm during, and until 90 days after the last dose of the trial medication * Provide written informed consent prior to any trial related procedure * Body weight of greater than or equal to (\>=)55.0 kg to less than (\<) 95.0 kg and a body mass index (BMI) between 18.5 and 29.9 kilogram per square meter (kg/m\^2) * Able to communicate well with the Investigator, understand the protocol requirements and restrictions, and willing to comply with the requirements of the entire trial * Non-smoker (= 0 cigarettes, pipes, cigars or other) from at least 3 months prior to start of trial * Electrocardiogram (ECG) recording (12-lead) without signs of clinically relevant pathology, in particular QTcB \< 450 milliseconds (ms) * Vital signs (systolic blood pressure, diastolic blood pressure and pulse) in supine position are within the normal range or show no clinically relevant deviation as judged by the Investigator
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 subject in the trial or that could interfere with the trial objectives, conduct or evaluation * History of gastrointestinal (GI) tract surgery, other GI tract diseases or acute GI tract infections within the last 2 weeks that could influence the GI absorption and/or motility according to the Investigator's opinion * Any clinically relevant abnormality in the safety laboratory parameters as judged by the Investigator * Positive results from serology examination for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) * Have an ascertained or presumptive contraindication or hypersensitivity to the active drug substance and/or formulations' ingredients * Have any clinically significant history of allergic conditions which the Investigator considers may affect the outcome of the trial * History or presence of drug abuse or alcohol abuse (as defined by the assessment of the investigator) at screening and on each admission * Blood donation or loss of more than 400 mL of blood within 3 months before the first administration of the investigational product * Administration of any investigational product or use of any investigational device within 60 days prior to first dosing that may affect the pharmacokinetics of the investigational product * Subjects who have used drugs that may affect the pharmacokinetics (PK) of PZQ from 15 days before the first administration of the investigational product until the last PK sample * Consumption of substances known to be potent inhibitors or inducers of cytochrome P450s (CYPs) within 2 weeks before the first administration of the investigational product * Unlikely to comply with the protocol requirements, instructions and trial-related restrictions * Non-acceptance of the study breakfast * Excessive consumption of beverages containing xanthine (greater than \[\>\] 5 cups of coffee a day or equivalent) and the inability to refrain from the use of caffeine-containing beverages from 48 hours before the first administration of the investigational product until discharge from the clinic * Subject 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 subjects * Legal incapacity or limited legal capacity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ) | Pre-dose,0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. AUC0-inf, adj was defined as the AUC0-inf adjusted for the actual administered dose of L-PZQ. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | — |
| Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. |
| Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | — |
| AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | — |
| Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | AUCextra was reported in terms of percentage of AUC0-inf. |
| Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. |
| Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | — |
| Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | 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 the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | 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. Vz/f after oral dose was influenced by the fraction absorbed. |
| Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. AUC0-inf, adj was defined as the AUC0-inf adjusted for the actual administered dose of D-PZQ and Racemate PZQ. |
| Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | Baseline up to end of treatment (up to Day 32) | An adverse event (AE) was defined as any untoward medical occurrence in a subject 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 stud drug. |
| Palatability Assessment Based on Visual Analog Scale (VAS) Score | Immediately and 2-5 minutes (min) after dosing on Day 1 of each treatment | Palatability was assessed in terms of Flavor, Smell, Sweetness, Overall liking of the medicine, Taste and Acceptability to swallow, each parameter assessed on a 0 to 100 millimeter (mm) visual analog scale (VAS), where 0 indicates Did not like and 100 indicates very much liked. Flavor, Smell, Sweetness and Overall liking of the medicine were evaluated immediately after taking the medication (Day 1, 0 Hour) and Taste and Acceptability to swallow were assessed 2-5 minutes post administration of medication. |
| Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters | Baseline up to end of treatment (up to Day 32) | Vital signs included oral body temperature, blood pressure and pulse rate. Body weight was recorded for physical examinations. The 12-lead ECGs were recorded after the subjects have rested for at least 5 minutes in supine position. The parameters heart rate (HR), RR, PR, QRS, QT and QTcB calculated by the Bazett formula. Laboratory investigation including chemistry, hematology and urinalysis. |
| Relative Bioavailability (Frel) of L-PZQ, D-PZQ, and Racemate PZQ | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment | Frel was calculated for Treatment A versus Treatment B only. It was calculated by using AUC0-∞, with treatment A as the Test and treatment B as the Reference. Frel = AUC0-inf (test) / AUC0-inf (reference). |
Countries
Germany
Participant flow
Recruitment details
First/Last subject (informed consent): 21 January 2015/21 January 2015. Study completion date: 09 March 2015. The study was conducted at one center in South Africa.
Pre-assignment details
Overall, 65 subjects were screened, for inclusion in this trial. Of which, 32 subjects were enrolled and randomized to a treatment sequence.
Participants by arm
| Arm | Count |
|---|---|
| Sequence A-B-C1-D1 Subjects randomized to treatment sequence A-B-C1-D1 received a single oral dose of 40 milligram per kilogram (40 mg/kg) of test oral dispersible tablet of praziquantel (ODT-PZQ) dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in third intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence A-B-C1-D2 Subjects randomized to treatment sequence A-B-C1-D2 received a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in third intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence A-B-C2-D1 Subjects randomized to treatment sequence A-B-C2-D1 received a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in third intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence A-B-C2-D2 Subjects randomized to treatment sequence A-B-C2-D2 received a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in third intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence A-B-D1-C1 Subjects randomized to treatment sequence A-B-D1-C1 received a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in third intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence A-B-D2-C1 Subjects randomized to treatment sequence A-B-D2-C1 received a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in third intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence A-B-D1-C2 Subjects randomized to treatment sequence A-B-D1-C2 received a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in third intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence A-B-D2-C2 Subjects randomized to treatment sequence A-B-D2-C2 received a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in first intervention period and then reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in second intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in third intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-C1-D1 Subjects randomized to treatment sequence B-A-C1-D1 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in third intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-C1-D2 Subjects randomized to treatment sequence B-A-C1-D2 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in third intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-C2-D1 Subjects randomized to treatment sequence B-A-C2-D1 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in third intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-C2-D2 Subjects randomized to treatment sequence B-A-C2-D2 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in third intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-D1-C1 Subjects randomized to treatment sequence B-A-D1-C1 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in third intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-D2-C1 Subjects randomized to treatment sequence B-A-D2-C1 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in third intervention period and then a single oral dose 20 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C1) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-D1-C2 Subjects randomized to treatment sequence B-A-D1-C2 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then a single oral dose 40 mg/kg of test ODT-PZQ dispersed in water without a meal (Treatment D1) in third intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Sequence B-A-D2-C2 Subjects randomized to treatment sequence B-A-D2-C2 received reference PZQ formulation (Cysticide tablet) at a single dose of 40 mg/kg given with water orally after a meal (Treatment B) in first intervention period and then a single oral dose of 40 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment A) in second intervention period and then reference PZQ formulation (Cysticide crushed tablets) at a single dose of 40 mg/kg given with water orally after a meal (Treatment D2) in third intervention period and then a single oral dose 60 mg/kg of test ODT-PZQ dispersed in water after a meal (Treatment C2) in fourth intervention period. A washout period of 7 days was maintained between each intervention period. | 2 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention Period 1 (2 Days) | Protocol Non-Compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Intervention Period 2 (2 Days) | Protocol Non-Compliance | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Intervention Period 3 (2 Days) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Sequence A-B-C1-D1 | Sequence A-B-C2-D1 | Sequence A-B-C2-D2 | Sequence A-B-D1-C1 | Sequence A-B-D2-C1 | Sequence A-B-D1-C2 | Sequence A-B-D2-C2 | Sequence B-A-C1-D1 | Sequence B-A-C1-D2 | Sequence B-A-C2-D1 | Sequence B-A-C2-D2 | Sequence B-A-D1-C1 | Sequence B-A-D2-C1 | Sequence B-A-D1-C2 | Sequence B-A-D2-C2 | Sequence A-B-C1-D2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants |
| Gender Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 32 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 31 | 4 / 32 | 1 / 15 | 6 / 15 | 0 / 14 | 3 / 15 |
| serious Total, serious adverse events | 0 / 31 | 0 / 32 | 0 / 15 | 0 / 15 | 0 / 14 | 0 / 15 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ)
AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. AUC0-inf, adj was defined as the AUC0-inf adjusted for the actual administered dose of L-PZQ.
Time frame: Pre-dose,0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The pharmacokinetic (PK) population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods. Here, 'N' (number of participants analyzed) signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ) | 1969.6 Hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 47.2 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ) | 2047.9 Hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 60.2 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ) | 345.4 Hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 69.5 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ) | 4871.3 Hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 42.2 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ) | 924.9 Hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 67.7 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ) | 1537.7 Hour*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 70.6 |
90% CI: [83.7, 110.6]
90% CI: [15.3, 22]
90% CI: [186.8, 265.6]
90% CI: [198.7, 285.3]
90% CI: [68.5, 98.3]
Secondary
Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ
λz was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods. Here, n signifies those subjects who were evaluable for specified isomers (L-PZQ and D-PZQ) or the racemate mixture of PZQ for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 0.151 1/h | Geometric Coefficient of Variation 34.7 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 0.155 1/h | Geometric Coefficient of Variation 34.3 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 0.210 1/h | Geometric Coefficient of Variation 49.1 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 0.150 1/h | Geometric Coefficient of Variation 33.8 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 0.157 1/h | Geometric Coefficient of Variation 35.8 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 0.181 1/h | Geometric Coefficient of Variation 46.8 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 0.184 1/h | Geometric Coefficient of Variation 38.8 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 0.362 1/h | Geometric Coefficient of Variation 72.2 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 0.175 1/h | Geometric Coefficient of Variation 37.2 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 0.165 1/h | Geometric Coefficient of Variation 37.8 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 0.159 1/h | Geometric Coefficient of Variation 19.4 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 0.161 1/h | Geometric Coefficient of Variation 24.4 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 0.142 1/h | Geometric Coefficient of Variation 29.1 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 0.166 1/h | Geometric Coefficient of Variation 34.9 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 0.131 1/h | Geometric Coefficient of Variation 30.1 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 0.159 1/h | Geometric Coefficient of Variation 31.2 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 0.226 1/h | Geometric Coefficient of Variation 43.5 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 0.165 1/h | Geometric Coefficient of Variation 30.2 |
Secondary
Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ
Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods. Here, n signifies those subjects who were evaluable for specified isomers (L-PZQ and D-PZQ) or the racemate mixture of PZQ for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 4.577 hours | Geometric Coefficient of Variation 34.7 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 3.305 hours | Geometric Coefficient of Variation 49.1 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 4.462 hours | Geometric Coefficient of Variation 34.3 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 4.618 hours | Geometric Coefficient of Variation 33.8 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 3.830 hours | Geometric Coefficient of Variation 46.8 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 4.408 hours | Geometric Coefficient of Variation 35.8 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 3.775 hours | Geometric Coefficient of Variation 38.8 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 1.916 hours | Geometric Coefficient of Variation 72.2 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 3.962 hours | Geometric Coefficient of Variation 37.2 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 4.346 hours | Geometric Coefficient of Variation 19.4 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 4.316 hours | Geometric Coefficient of Variation 24.4 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 4.202 hours | Geometric Coefficient of Variation 37.8 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 4.168 hours | Geometric Coefficient of Variation 34.9 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 5.281 hours | Geometric Coefficient of Variation 30.1 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 4.889 hours | Geometric Coefficient of Variation 29.1 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 3.072 hours | Geometric Coefficient of Variation 43.5 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 4.204 hours | Geometric Coefficient of Variation 30.2 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 4.347 hours | Geometric Coefficient of Variation 31.2 |
Secondary
Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate 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, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods. Here, n signifies those subjects who were evaluable for specified isomers (L-PZQ and D-PZQ) or the racemate mixture of PZQ for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 187.2 Liter/hour | Geometric Coefficient of Variation 33.3 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 716.8 Liter/hour | Geometric Coefficient of Variation 45 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 293.3 Liter/hour | Geometric Coefficient of Variation 30.7 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 170.7 Liter/hour | Geometric Coefficient of Variation 42.6 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 691.3 Liter/hour | Geometric Coefficient of Variation 57.9 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 271.0 Liter/hour | Geometric Coefficient of Variation 42.6 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 316.7 Liter/hour | Geometric Coefficient of Variation 47.6 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 2028.4 Liter/hour | Geometric Coefficient of Variation 60 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 548.7 Liter/hour | Geometric Coefficient of Variation 46.4 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 145.5 Liter/hour | Geometric Coefficient of Variation 41.6 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 438.5 Liter/hour | Geometric Coefficient of Variation 45.8 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 217.1 Liter/hour | Geometric Coefficient of Variation 41 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 271.6 Liter/hour | Geometric Coefficient of Variation 62.8 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 1466.9 Liter/hour | Geometric Coefficient of Variation 60.6 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 455.6 Liter/hour | Geometric Coefficient of Variation 60.1 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 971.1 Liter/hour | Geometric Coefficient of Variation 69.5 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 366.1 Liter/hour | Geometric Coefficient of Variation 43.2 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 227.6 Liter/hour | Geometric Coefficient of Variation 43.7 |
Secondary
Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate 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. Vz/f after oral dose was influenced by the fraction absorbed.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods. Here, n signifies those subjects who were evaluable for specified isomers (L-PZQ and D-PZQ) or the racemate mixture of PZQ for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1236.0 Liters | Geometric Coefficient of Variation 43.7 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1887.7 Liters | Geometric Coefficient of Variation 37.3 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 3417.6 Liters | Geometric Coefficient of Variation 37 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1137.4 Liters | Geometric Coefficient of Variation 52.9 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 3820.4 Liters | Geometric Coefficient of Variation 57.5 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1723.7 Liters | Geometric Coefficient of Variation 53.3 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 2987.7 Liters | Geometric Coefficient of Variation 60.4 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 5605.6 Liters | Geometric Coefficient of Variation 63.9 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1810.1 Liters | Geometric Coefficient of Variation 64.8 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 912.1 Liters | Geometric Coefficient of Variation 40 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 2658.4 Liters | Geometric Coefficient of Variation 59.9 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1352.0 Liters | Geometric Coefficient of Variation 42.7 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 2069.2 Liters | Geometric Coefficient of Variation 70.5 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 8820.4 Liters | Geometric Coefficient of Variation 55.3 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 3213.2 Liters | Geometric Coefficient of Variation 61.7 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 2220.2 Liters | Geometric Coefficient of Variation 38.4 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1427.2 Liters | Geometric Coefficient of Variation 41.5 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 4304.4 Liters | Geometric Coefficient of Variation 50.6 |
Secondary
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ
AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. AUC0-inf, adj was defined as the AUC0-inf adjusted for the actual administered dose of D-PZQ and Racemate PZQ.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | racemate PZQ | 9627.2 h*ng/mL | Geometric Coefficient of Variation 28 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | D-PZQ | 7542.3 h*ng/mL | Geometric Coefficient of Variation 29.2 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | racemate PZQ | 10446.9 h*ng/mL | Geometric Coefficient of Variation 40.7 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | D-PZQ | 8292.7 h*ng/mL | Geometric Coefficient of Variation 39.4 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | racemate PZQ | 2569.5 h*ng/mL | Geometric Coefficient of Variation 46.5 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | D-PZQ | 2226.0 h*ng/mL | Geometric Coefficient of Variation 46.1 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | D-PZQ | 14685.8 h*ng/mL | Geometric Coefficient of Variation 35.5 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | racemate PZQ | 19679.5 h*ng/mL | Geometric Coefficient of Variation 35.4 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | D-PZQ | 4996.0 h*ng/mL | Geometric Coefficient of Variation 58.5 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | racemate PZQ | 5956.0 h*ng/mL | Geometric Coefficient of Variation 57.7 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | racemate PZQ | 8091.8 h*ng/mL | Geometric Coefficient of Variation 42.3 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ | D-PZQ | 6508.9 h*ng/mL | Geometric Coefficient of Variation 41.8 |
Secondary
AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 7405.9 h*ng/mL | Geometric Coefficient of Variation 28.2 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 1928.0 h*ng/mL | Geometric Coefficient of Variation 47.4 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 9476.3 h*ng/mL | Geometric Coefficient of Variation 26.9 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 8131.4 h*ng/mL | Geometric Coefficient of Variation 39 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 1994.0 h*ng/mL | Geometric Coefficient of Variation 61.1 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 10266.0 h*ng/mL | Geometric Coefficient of Variation 40.2 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 2169.2 h*ng/mL | Geometric Coefficient of Variation 46.7 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 300.5 h*ng/mL | Geometric Coefficient of Variation 75.5 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 2515.2 h*ng/mL | Geometric Coefficient of Variation 47 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 14367.2 h*ng/mL | Geometric Coefficient of Variation 34 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 4770.1 h*ng/mL | Geometric Coefficient of Variation 41.9 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 19262.2 h*ng/mL | Geometric Coefficient of Variation 34.1 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 4740.6 h*ng/mL | Geometric Coefficient of Variation 56.5 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 863.7 h*ng/mL | Geometric Coefficient of Variation 70.2 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 5694.0 h*ng/mL | Geometric Coefficient of Variation 55.6 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 1342.6 h*ng/mL | Geometric Coefficient of Variation 86 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 7929.9 h*ng/mL | Geometric Coefficient of Variation 41.9 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 6365.5 h*ng/mL | Geometric Coefficient of Variation 41.5 |
Secondary
Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ
AUCextra was reported in terms of percentage of AUC0-inf.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods. Here, n signifies those subjects who were evaluable for specified isomers (L-PZQ and D-PZQ) or the racemate mixture of PZQ for each arm, respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 1.86 percentage of AUC0-inf | Geometric Coefficient of Variation 51.4 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1.10 percentage of AUC0-inf | Geometric Coefficient of Variation 101 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1.30 percentage of AUC0-inf | Geometric Coefficient of Variation 97.4 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1.24 percentage of AUC0-inf | Geometric Coefficient of Variation 104.5 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 2.23 percentage of AUC0-inf | Geometric Coefficient of Variation 66.3 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1.48 percentage of AUC0-inf | Geometric Coefficient of Variation 90.4 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 2.26 percentage of AUC0-inf | Geometric Coefficient of Variation 56 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1.85 percentage of AUC0-inf | Geometric Coefficient of Variation 59 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 5.25 percentage of AUC0-inf | Geometric Coefficient of Variation 97.6 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1.51 percentage of AUC0-inf | Geometric Coefficient of Variation 106.9 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 1.60 percentage of AUC0-inf | Geometric Coefficient of Variation 79.9 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1.38 percentage of AUC0-inf | Geometric Coefficient of Variation 133.4 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 3.69 percentage of AUC0-inf | Geometric Coefficient of Variation 110.6 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 5.52 percentage of AUC0-inf | Geometric Coefficient of Variation 72.9 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 3.05 percentage of AUC0-inf | Geometric Coefficient of Variation 117.2 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ (n= 30,30,14,15,14,14) | 2.30 percentage of AUC0-inf | Geometric Coefficient of Variation 63.7 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ (n= 30,30,15,15,14,15) | 1.38 percentage of AUC0-inf | Geometric Coefficient of Variation 104.1 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ (n= 30,30,15,15,14,15) | 1.60 percentage of AUC0-inf | Geometric Coefficient of Variation 97.6 |
Secondary
Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | D-PZQ | 2330 ng/mL | Geometric Coefficient of Variation 30.7 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | L-PZQ | 881.3 ng/mL | Geometric Coefficient of Variation 57.2 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | Racemate PZQ | 3250 ng/mL | Geometric Coefficient of Variation 34.6 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | D-PZQ | 2179 ng/mL | Geometric Coefficient of Variation 33 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | L-PZQ | 762.6 ng/mL | Geometric Coefficient of Variation 59.5 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | Racemate PZQ | 2974 ng/mL | Geometric Coefficient of Variation 37.2 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | D-PZQ | 786.3 ng/mL | Geometric Coefficient of Variation 41.5 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | L-PZQ | 154.6 ng/mL | Geometric Coefficient of Variation 80.4 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | Racemate PZQ | 949.9 ng/mL | Geometric Coefficient of Variation 45.1 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | D-PZQ | 3234 ng/mL | Geometric Coefficient of Variation 20 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | L-PZQ | 1548 ng/mL | Geometric Coefficient of Variation 32.6 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | Racemate PZQ | 4780 ng/mL | Geometric Coefficient of Variation 23.3 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | D-PZQ | 838.5 ng/mL | Geometric Coefficient of Variation 65.7 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | L-PZQ | 189.3 ng/mL | Geometric Coefficient of Variation 104 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | Racemate PZQ | 1042 ng/mL | Geometric Coefficient of Variation 70.7 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | L-PZQ | 446.3 ng/mL | Geometric Coefficient of Variation 87.6 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | Racemate PZQ | 2040 ng/mL | Geometric Coefficient of Variation 40.9 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ | D-PZQ | 1556 ng/mL | Geometric Coefficient of Variation 35.8 |
Secondary
Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters
Vital signs included oral body temperature, blood pressure and pulse rate. Body weight was recorded for physical examinations. The 12-lead ECGs were recorded after the subjects have rested for at least 5 minutes in supine position. The parameters heart rate (HR), RR, PR, QRS, QT and QTcB calculated by the Bazett formula. Laboratory investigation including chemistry, hematology and urinalysis.
Time frame: Baseline up to end of treatment (up to Day 32)
Population: The safety population included all randomized subjects who received at least 1 dose of the trial medication and who had follow-up safety assessments.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters | 0 subjects |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters | 0 subjects |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters | 0 subjects |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters | 0 subjects |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters | 0 subjects |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters | 0 subjects |
Secondary
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation
An adverse event (AE) was defined as any untoward medical occurrence in a subject 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 stud drug.
Time frame: Baseline up to end of treatment (up to Day 32)
Population: The safety population included all randomized subjects who received at least 1 dose of the trial medication and who had follow-up safety assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 0 subjects |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 5 subjects |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 0 subjects |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 0 subjects |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 4 subjects |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 0 subjects |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 0 subjects |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 1 subjects |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 0 subjects |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 0 subjects |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 6 subjects |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 0 subjects |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 0 subjects |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 0 subjects |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 0 subjects |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAEs | 3 subjects |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 0 subjects |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation | Serious TEAEs | 0 subjects |
Secondary
Palatability Assessment Based on Visual Analog Scale (VAS) Score
Palatability was assessed in terms of Flavor, Smell, Sweetness, Overall liking of the medicine, Taste and Acceptability to swallow, each parameter assessed on a 0 to 100 millimeter (mm) visual analog scale (VAS), where 0 indicates Did not like and 100 indicates very much liked. Flavor, Smell, Sweetness and Overall liking of the medicine were evaluated immediately after taking the medication (Day 1, 0 Hour) and Taste and Acceptability to swallow were assessed 2-5 minutes post administration of medication.
Time frame: Immediately and 2-5 minutes (min) after dosing on Day 1 of each treatment
Population: The safety population included all randomized subjects who received at least 1 dose of the trial medication and who had follow-up safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Overall liking | 46.8 millimiter (mm) | Standard Deviation 32.29 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Smell | 60.7 millimiter (mm) | Standard Deviation 25.91 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day1,2-5 Min After Medicine:Acceptable to Swallow | 68.2 millimiter (mm) | Standard Deviation 30.9 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Sweetness | 47.3 millimiter (mm) | Standard Deviation 27.12 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Flavour | 43.4 millimiter (mm) | Standard Deviation 30.25 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 2-5 Min After Medicine: Taste in Mouth | 39.7 millimiter (mm) | Standard Deviation 31.34 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day1,2-5 Min After Medicine:Acceptable to Swallow | 62.5 millimiter (mm) | Standard Deviation 26.48 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Smell | 61.5 millimiter (mm) | Standard Deviation 24.57 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 2-5 Min After Medicine: Taste in Mouth | 44.9 millimiter (mm) | Standard Deviation 30.74 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Overall liking | 51.3 millimiter (mm) | Standard Deviation 30.67 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Flavour | 44.6 millimiter (mm) | Standard Deviation 32.18 |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Sweetness | 41.2 millimiter (mm) | Standard Deviation 32.55 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Overall liking | 50.2 millimiter (mm) | Standard Deviation 33.93 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Flavour | 50.3 millimiter (mm) | Standard Deviation 32.24 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Smell | 47.5 millimiter (mm) | Standard Deviation 33.64 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day1,2-5 Min After Medicine:Acceptable to Swallow | 55.7 millimiter (mm) | Standard Deviation 33.16 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Sweetness | 51.4 millimiter (mm) | Standard Deviation 31.91 |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 2-5 Min After Medicine: Taste in Mouth | 44.7 millimiter (mm) | Standard Deviation 31.23 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Flavour | 46.1 millimiter (mm) | Standard Deviation 33.14 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Smell | 51.1 millimiter (mm) | Standard Deviation 26.11 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Sweetness | 50.7 millimiter (mm) | Standard Deviation 33.02 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Overall liking | 40.7 millimiter (mm) | Standard Deviation 31.6 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 2-5 Min After Medicine: Taste in Mouth | 35.0 millimiter (mm) | Standard Deviation 32.21 |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day1,2-5 Min After Medicine:Acceptable to Swallow | 39.9 millimiter (mm) | Standard Deviation 33.71 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Smell | 51.7 millimiter (mm) | Standard Deviation 29.65 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day1,2-5 Min After Medicine:Acceptable to Swallow | 61.1 millimiter (mm) | Standard Deviation 31.51 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Flavour | 55.9 millimiter (mm) | Standard Deviation 31.2 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 2-5 Min After Medicine: Taste in Mouth | 46.7 millimiter (mm) | Standard Deviation 31.29 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Overall liking | 48.8 millimiter (mm) | Standard Deviation 30.24 |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Sweetness | 61.6 millimiter (mm) | Standard Deviation 21.19 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Overall liking | 13.7 millimiter (mm) | Standard Deviation 20.07 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Smell | 29.4 millimiter (mm) | Standard Deviation 29.34 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 2-5 Min After Medicine: Taste in Mouth | 14.4 millimiter (mm) | Standard Deviation 21.07 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Flavour | 20.1 millimiter (mm) | Standard Deviation 20.82 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day1,2-5 Min After Medicine:Acceptable to Swallow | 23.1 millimiter (mm) | Standard Deviation 29.19 |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Palatability Assessment Based on Visual Analog Scale (VAS) Score | Day 1, 0 Hour: Sweetness | 12.9 millimiter (mm) | Standard Deviation 21.31 |
Secondary
Relative Bioavailability (Frel) of L-PZQ, D-PZQ, and Racemate PZQ
Frel was calculated for Treatment A versus Treatment B only. It was calculated by using AUC0-∞, with treatment A as the Test and treatment B as the Reference. Frel = AUC0-inf (test) / AUC0-inf (reference).
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Relative Bioavailability (Frel) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 96.175 percent bioavailability | Geometric Coefficient of Variation 46.7 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Relative Bioavailability (Frel) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 90.951 percent bioavailability | Geometric Coefficient of Variation 27.52 |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Relative Bioavailability (Frel) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 92.2 percent bioavailability | Geometric Coefficient of Variation 21.6 |
Secondary
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 0.000 hours |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 0.000 hours |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 0.000 hours |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 0.000 hours |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 0.000 hours |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 0.000 hours |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 0.000 hours |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 0.000 hours |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 0.000 hours |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 0.000 hours |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 0.000 hours |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 0.000 hours |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 0.000 hours |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 0.000 hours |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 0.000 hours |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 0.000 hours |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 0.000 hours |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 0.000 hours |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
Population: The PK population included all subjects who completed the study and for whom primary PK parameters could be calculated for the first two treatment periods.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 3.000 hours |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 3.000 hours |
| Treatment A: 40 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 3.000 hours |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 2.000 hours |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 1.500 hours |
| Treatment B: 40 mg/kg Cysticide Tablet After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 1.750 hours |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 3.500 hours |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 4.000 hours |
| Treatment C1: 20 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 3.500 hours |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 4.000 hours |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 3.000 hours |
| Treatment C2: 60 mg/kg Test ODT-PZQ After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 3.500 hours |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 4.500 hours |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 4.250 hours |
| Treatment D1: 40 mg/kg Test ODT-PZQ Without Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 4.500 hours |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | L-PZQ | 2.500 hours |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | racemate PZQ | 2.500 hours |
| Treatment D2: 40 mg/kg Cysticide Crushed Tablets After Meal | Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ | D-PZQ | 3.500 hours |