Healthy
Conditions
Keywords
Healthy, Praziquantel, L-PZQ, PZQ, MSC2499550A, Bioavailability, Pharmacokinetics
Brief summary
This is a phase I, open-label, randomized, 5 period, crossover, single-center trial. The purpose of this trial is to assess the relative bio-availability of L-praziquantel (L-PZQ \[MSC2499550A\]) oral dispersible tablet (ODT) formulation (150 milligram \[mg\]) versus the current marketed racemate praziquantel (PZQ) (Cysticide® 500 mg) formulation in healthy male volunteers under fed conditions.
Interventions
DRUGMSC2499550A
Subjects will receive a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water under fed condition in one of the intervention periods. There will be a wash-out period of at least 7 days between each intervention period.
DRUGCysticide
Subjects will receive a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water, under fed condition in one of the intervention periods. There will be a wash-out period of at least 7 days between each of the intervention period.
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 aged 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 * Written informed consent prior to any trial related procedure * Have a body weight of greater than or equal to (\>=) 55.0 kilogram (kg) to less than (\<) 95.0 kg and a body mass index (BMI) of 18.5 to 29.9 kilogram per square meter (kg/m\^2) (inclusive) * Able to communicate well with the Investigator, understanding the protocol requirements and restrictions, and willing to comply with the requirements of the entire trial * Non-smoker (= 0 cigarettes, pipes, cigars or others) since at least 3 months * Electrocardiogram (ECG) recording (12-lead) without signs of clinically relevant pathology in particular corrected QT Interval (QTc) (Bazett) \< 450 milliseconds (ms) * Vital signs (systolic and diastolic blood pressure, pulse) in supine position and body temperature within the normal range or showing no clinically relevant deviation as judged by the medical Investigator
Exclusion criteria
* Any surgical or medical condition, including findings in the medical history or in the prestudy 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 study or that could interfere with the study objectives, conduct or evaluation * History of surgery of the gastrointestinal tract (GI), history of other GI tract diseases, or acute GI tract infections in the last 2 weeks, which 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 * Have positive results from serology examination for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) * Allergy: ascertained or presumptive hypersensitivity to the active drug substance and/or formulations ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the trial * History or presence of drug abuse (amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine (phenylcyclohexalpiperidine), tetrahydrocannabinol, tricyclic antidepressants, methadone, methamphetamine, oxycodone and propoxyphene) or alcohol abuse at screening and on each admission as defined by the Investigator * Loss or donation of more than 400 milliliter (mL) of blood within 90 days prior to first praziquantel (PZQ) administration * Administration of any investigational product or use of any investigational device within 60 days prior to first PZQ administration * Subjects who have used drugs that may affect the pharmacokinetics (PK) of PZQ from 14 days before dosing until the last PK sample, for example, phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, oral ketoconazole, on discretion of the Investigator * Consumption of substances known to be potent inhibitors or inducers of cytochrome -P450 enzymes (CYP P450s) such as grapefruit juice, grapefruit juice containing products, and herbal remedies or dietary supplements containing St. John's Wort, in the 2 weeks before dosing * Unlikely to comply with the protocol requirements, instructions and trial-related restrictions, for example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial * Non-acceptance of study breakfast (for example, vegetarians, vegans and subjects who follow special diets) * Excessive consumption of beverages -containing xanthine (\> 5 cups ) of coffee a day, or equivalent or inability to stop consuming caffeine from 48 hours prior to drug administration until discharge from the clinic * 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 (for example, persons kept in detention) * 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) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | Time prior to the first measurable (non-zero) concentration (tlag) of drug L-PZQ |
| Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | The AUC (0-t) was defined as the area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration at or above the lower limit of quantification (AUC0-t) of L-PZQ. |
| Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | Extrapolated AUC from time tlast to infinity given as percentage from AUC0-inf. AUCextra =(last predicted concentration \[Clast pred\] divided by terminal elimination rate constant \[lambda z\]) divided by AUC0-inf., where Clast pred is the last predicted concentration. |
| Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | — |
| Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | The apparent terminal half-life was calculated by dividing natural log 2 with lambda z (ln2/lambda Z); where lambda Z is the terminal rate constant. |
| Relative Bioavailability (Frel) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | Relative bioavailability (Frel) was calculated for L-PZQ only (treatment A versus treatment B) using the formula: Frel = (AUC0-inf (test or Treatment A)/AUC0-inf (reference or treatment B)) multiplied by 100. |
| Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | — |
| Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | The CL/f of L-PZQ was a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F of L-PZQ from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf). |
| Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | The Vz/f was defined as the theoretical volume in which the total amount of L-PZQ required to uniformly distribute to produce the desired plasma concentration of L-PZQ. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant (lambda z) (Vz/f=Dose/( AUC0-inf\* lambda z). |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | From the first dose of study drug administration up to 3-10 days after the last dose of the study drug (up to a maximum of 7 weeks) | An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. 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. TEAEs were adverse events that occurred between the first dose of study drug and up to 3-10 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Subjects who discontinued and who died due to TEAEs were also reported. |
| Palatability Score | 0 min for flavor, smell, sweetness, overall liking; 2-5 minutes post dose for taste in mouth and acceptability on Day 1 | Each administration was assessed at 0 minutes on Day 1 for flavor, smell, sweetness, overall liking of the medicine and at 2-5 minutes on Day 1 for taste in mouth and acceptability to swallow using a modified 100 millimeter (mm), visual analog scale (VAS) incorporating a facial hedonic scale, where lower score (0) indicates not acceptable/not liked at all and higher score (100) indicates very acceptable/liked very much. |
| Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | From the first dose of study drug administration up to 3-10 days after the last dose of the study drug (up to a maximum of 7 weeks) | Any clinically significant changes in laboratory evaluations ECGs,physical examination (body weight) and vital signs (temperature, blood pressure, pulse rate) were recorded as treatment emergent adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, hematocrit, red blood cell count, mean cell hemoglobin \[MCH\], MCH concentration, mean cell volume, white cell count, platelets, neutrophils, lymphocytes, monocytes, eosinophils, Basophils); serum chemistry (sodium, potassium, calcium, inorganic phosphate, creatinine, total protein, albumin, urea, uric acid, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] gamma glutamyl transpeptidase, total bilirubin, alkaline phosphatase, glucose, triglycerides cholesterol); urinalysis (protein, glucose, ketones, pH, blood, leukocytes, nitrite); The 12-lead ECGs were recorded after the subjects had rested for at least 5 minutes in supine position. |
| Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) | Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose | The lambda z was calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. |
Countries
Germany
Participant flow
Pre-assignment details
Subjects were randomized to receive a sequence of 5 treatments over 5 treatment periods. A total of 36 were enrolled subjects, three in each of the 12 possible sequences were distributed.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Subjects randomized to receive a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water, current praziquantel (PZQ) formulation (Cysticide®) at 40 mg/kg with water under fed conditions; MSC2499550A formulation at 10 mg/kg or 30 mg/kg dispersed in water under fed condition; MSC2499550A formulation at 20 mg/kg dispersed in water under fasted condition; MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed condition in one of the intervention periods. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Washout Period 4 (7 Days) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 26.3 Years STANDARD_DEVIATION 6.99 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 36 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 | 8 / 36 | 17 / 36 | 4 / 18 | 4 / 17 | 5 / 35 | 1 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 18 | 0 / 17 | 0 / 35 | 0 / 36 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of participants analyzed below (Measured Values) reflects number of participants with non-missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment | 825.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 101 |
| Treatment B | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment | 2066.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 64.7 |
| Treatment C1 | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment | 216.7 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 102.8 |
| Treatment C2 | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment | 2324.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 76.4 |
| Treatment D | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment | 506.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 100 |
| Treatment E | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment | 954.5 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 96.4 |
90% CI: [34.7, 46]
90% CI: [22.5, 33.2]
90% CI: [214, 316.4]
90% CI: [143.9, 194]
90% CI: [99.8, 134.1]
Secondary
Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ)
The lambda z was calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase.
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of participants analyzed below (Measured Values) reflects number of participants with non-missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) | 0.250 per hour (1/hour) | Geometric Coefficient of Variation 53.9 |
| Treatment B | Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) | 0.181 per hour (1/hour) | Geometric Coefficient of Variation 46.3 |
| Treatment C1 | Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) | 0.432 per hour (1/hour) | Geometric Coefficient of Variation 88.6 |
| Treatment C2 | Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) | 0.206 per hour (1/hour) | Geometric Coefficient of Variation 31.9 |
| Treatment D | Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) | 0.244 per hour (1/hour) | Geometric Coefficient of Variation 62.3 |
| Treatment E | Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) | 0.264 per hour (1/hour) | Geometric Coefficient of Variation 65.2 |
Secondary
Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ)
The apparent terminal half-life was calculated by dividing natural log 2 with lambda z (ln2/lambda Z); where lambda Z is the terminal rate constant.
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of participants analyzed below (Measured Values) reflects number of participants with non-missing values.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ) | 2.984 hour |
| Treatment B | Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ) | 3.788 hour |
| Treatment C1 | Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ) | 1.059 hour |
| Treatment C2 | Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ) | 3.296 hour |
| Treatment D | Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ) | 2.801 hour |
| Treatment E | Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ) | 2.711 hour |
Secondary
Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ)
The CL/f of L-PZQ was a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F of L-PZQ from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf).
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of participants analyzed below (Measured Values) reflects number of participants with non-missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ) | 1665 Liter per hour | Geometric Coefficient of Variation 94.3 |
| Treatment B | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ) | 667.3 Liter per hour | Geometric Coefficient of Variation 60.1 |
| Treatment C1 | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ) | 3091 Liter per hour | Geometric Coefficient of Variation 92.9 |
| Treatment C2 | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ) | 923.5 Liter per hour | Geometric Coefficient of Variation 71.4 |
| Treatment D | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ) | 2729 Liter per hour | Geometric Coefficient of Variation 95.4 |
| Treatment E | Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ) | 1440 Liter per hour | Geometric Coefficient of Variation 89.3 |
Secondary
Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ)
The Vz/f was defined as the theoretical volume in which the total amount of L-PZQ required to uniformly distribute to produce the desired plasma concentration of L-PZQ. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant (lambda z) (Vz/f=Dose/( AUC0-inf\* lambda z).
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of participants analyzed below (Measured Values) reflects number of participants with non-missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ) | 6671 Liter | Geometric Coefficient of Variation 62.9 |
| Treatment B | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ) | 3685 Liter | Geometric Coefficient of Variation 62.8 |
| Treatment C1 | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ) | 7155 Liter | Geometric Coefficient of Variation 72.4 |
| Treatment C2 | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ) | 4478 Liter | Geometric Coefficient of Variation 62.8 |
| Treatment D | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ) | 11170 Liter | Geometric Coefficient of Variation 81.1 |
| Treatment E | Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ) | 5452 Liter | Geometric Coefficient of Variation 62.4 |
Secondary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment
The AUC (0-t) was defined as the area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration at or above the lower limit of quantification (AUC0-t) of L-PZQ.
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: The pharmacokinetic (PK) population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment | 791.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 103.6 |
| Treatment B | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment | 2010.7 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 66.1 |
| Treatment C1 | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment | 186.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 107.5 |
| Treatment C2 | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment | 2273.5 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 77.9 |
| Treatment D | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment | 464.7 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 102.9 |
| Treatment E | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of L-Praziquantel (L-PZQ) After Dose Adjustment | 918.0 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 98.7 |
Secondary
Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ)
Extrapolated AUC from time tlast to infinity given as percentage from AUC0-inf. AUCextra =(last predicted concentration \[Clast pred\] divided by terminal elimination rate constant \[lambda z\]) divided by AUC0-inf., where Clast pred is the last predicted concentration.
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: PK population: all randomized subjects treated according to protocol without relevant violations with respect to factors likely to affect comparability of PK results \& availability of AUC0-inf for MSC2499550A in periods 1 \& 2. Number of participants analyzed below (Measured Values) reflects number of participants with non-missing values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ) | 3.40 Percent extrapolated | Geometric Coefficient of Variation 73.8 |
| Treatment B | Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ) | 2.20 Percent extrapolated | Geometric Coefficient of Variation 65.2 |
| Treatment C1 | Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ) | 6.62 Percent extrapolated | Geometric Coefficient of Variation 85.3 |
| Treatment C2 | Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ) | 1.80 Percent extrapolated | Geometric Coefficient of Variation 72.7 |
| Treatment D | Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ) | 5.81 Percent extrapolated | Geometric Coefficient of Variation 82.5 |
| Treatment E | Extrapolated Area Under the Concentration Time Curve (AUC) From Time Tlast to Infinity Given as Percentage From AUC0-inf (AUCextra) of L-Praziquantel (L-PZQ) | 3.15 Percent extrapolated | Geometric Coefficient of Variation 66.5 |
Secondary
Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: The PK population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | 378.83 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 114.1 |
| Treatment B | Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | 727.27 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 63.3 |
| Treatment C1 | Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | 89.93 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 92.2 |
| Treatment C2 | Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | 1051.76 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 83.6 |
| Treatment D | Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | 131.06 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 110.6 |
| Treatment E | Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | 471.18 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 99.5 |
Secondary
Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events
Any clinically significant changes in laboratory evaluations ECGs,physical examination (body weight) and vital signs (temperature, blood pressure, pulse rate) were recorded as treatment emergent adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, hematocrit, red blood cell count, mean cell hemoglobin \[MCH\], MCH concentration, mean cell volume, white cell count, platelets, neutrophils, lymphocytes, monocytes, eosinophils, Basophils); serum chemistry (sodium, potassium, calcium, inorganic phosphate, creatinine, total protein, albumin, urea, uric acid, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] gamma glutamyl transpeptidase, total bilirubin, alkaline phosphatase, glucose, triglycerides cholesterol); urinalysis (protein, glucose, ketones, pH, blood, leukocytes, nitrite); The 12-lead ECGs were recorded after the subjects had rested for at least 5 minutes in supine position.
Time frame: From the first dose of study drug administration up to 3-10 days after the last dose of the study drug (up to a maximum of 7 weeks)
Population: The safety analysis set consisted of all subjects who received at least one dose of the trial medication and who had follow-up safety assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Laboratory abnormalities | 0 Subjects |
| Treatment A | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | ECG abnormalities | 0 Subjects |
| Treatment A | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Vital signs abnormalities | 0 Subjects |
| Treatment A | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Physical signs abnormalities | 0 Subjects |
| Treatment B | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Vital signs abnormalities | 0 Subjects |
| Treatment B | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | ECG abnormalities | 0 Subjects |
| Treatment B | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Laboratory abnormalities | 0 Subjects |
| Treatment B | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Physical signs abnormalities | 0 Subjects |
| Treatment C1 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Physical signs abnormalities | 0 Subjects |
| Treatment C1 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Vital signs abnormalities | 0 Subjects |
| Treatment C1 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | ECG abnormalities | 0 Subjects |
| Treatment C1 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Laboratory abnormalities | 0 Subjects |
| Treatment C2 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Laboratory abnormalities | 0 Subjects |
| Treatment C2 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Physical signs abnormalities | 0 Subjects |
| Treatment C2 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | ECG abnormalities | 0 Subjects |
| Treatment C2 | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Vital signs abnormalities | 0 Subjects |
| Treatment D | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Vital signs abnormalities | 0 Subjects |
| Treatment D | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Physical signs abnormalities | 0 Subjects |
| Treatment D | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | ECG abnormalities | 0 Subjects |
| Treatment D | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Laboratory abnormalities | 0 Subjects |
| Treatment E | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | ECG abnormalities | 0 Subjects |
| Treatment E | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Vital signs abnormalities | 0 Subjects |
| Treatment E | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Physical signs abnormalities | 0 Subjects |
| Treatment E | Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events | Laboratory abnormalities | 0 Subjects |
Secondary
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
An Adverse Event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. 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. TEAEs were adverse events that occurred between the first dose of study drug and up to 3-10 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Subjects who discontinued and who died due to TEAEs were also reported.
Time frame: From the first dose of study drug administration up to 3-10 days after the last dose of the study drug (up to a maximum of 7 weeks)
Population: The safety analysis set consisted of all subjects who received at least one dose of the trial medication and who had follow-up safety assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 8 Subjects |
| Treatment A | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 0 Subjects |
| Treatment A | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 0 Subjects |
| Treatment A | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to death | 0 Subjects |
| Treatment B | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 0 Subjects |
| Treatment B | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 0 Subjects |
| Treatment B | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 17 Subjects |
| Treatment B | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to death | 0 Subjects |
| Treatment C1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to death | 0 Subjects |
| Treatment C1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 0 Subjects |
| Treatment C1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 0 Subjects |
| Treatment C1 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 4 Subjects |
| Treatment C2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 4 Subjects |
| Treatment C2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to death | 0 Subjects |
| Treatment C2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 0 Subjects |
| Treatment C2 | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 0 Subjects |
| Treatment D | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 0 Subjects |
| Treatment D | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to death | 0 Subjects |
| Treatment D | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 0 Subjects |
| Treatment D | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 5 Subjects |
| Treatment E | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 0 Subjects |
| Treatment E | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to discontinuation | 0 Subjects |
| Treatment E | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs leading to death | 0 Subjects |
| Treatment E | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 1 Subjects |
Secondary
Palatability Score
Each administration was assessed at 0 minutes on Day 1 for flavor, smell, sweetness, overall liking of the medicine and at 2-5 minutes on Day 1 for taste in mouth and acceptability to swallow using a modified 100 millimeter (mm), visual analog scale (VAS) incorporating a facial hedonic scale, where lower score (0) indicates not acceptable/not liked at all and higher score (100) indicates very acceptable/liked very much.
Time frame: 0 min for flavor, smell, sweetness, overall liking; 2-5 minutes post dose for taste in mouth and acceptability on Day 1
Population: The safety analysis set consisted of all subjects who received at least one dose of the trial medication and who had follow-up safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Palatability Score | Flavor: Day 1: 0 min | 67.5 millimeter (mm) | Standard Deviation 22.19 |
| Treatment A | Palatability Score | Smell: Day 1: 0 min | 63.1 millimeter (mm) | Standard Deviation 21.63 |
| Treatment A | Palatability Score | Taste in Mouth: Day 1:2-5 minutes after medication | 50.9 millimeter (mm) | Standard Deviation 26.42 |
| Treatment A | Palatability Score | Acceptable to swallow:Day1:2-5min after medication | 80.7 millimeter (mm) | Standard Deviation 17.57 |
| Treatment A | Palatability Score | Overall liking of Medicine: Day 1: 0 min | 67.8 millimeter (mm) | Standard Deviation 21.75 |
| Treatment A | Palatability Score | Sweetness: Day 1: 0 min | 74.8 millimeter (mm) | Standard Deviation 19.42 |
| Treatment B | Palatability Score | Flavor: Day 1: 0 min | 45.8 millimeter (mm) | Standard Deviation 24.04 |
| Treatment B | Palatability Score | Taste in Mouth: Day 1:2-5 minutes after medication | 39.5 millimeter (mm) | Standard Deviation 26.12 |
| Treatment B | Palatability Score | Smell: Day 1: 0 min | 56.4 millimeter (mm) | Standard Deviation 26.32 |
| Treatment B | Palatability Score | Acceptable to swallow:Day1:2-5min after medication | 59.2 millimeter (mm) | Standard Deviation 27.65 |
| Treatment B | Palatability Score | Sweetness: Day 1: 0 min | 30.5 millimeter (mm) | Standard Deviation 20.8 |
| Treatment B | Palatability Score | Overall liking of Medicine: Day 1: 0 min | 47.0 millimeter (mm) | Standard Deviation 28.22 |
| Treatment C1 | Palatability Score | Overall liking of Medicine: Day 1: 0 min | 69.7 millimeter (mm) | Standard Deviation 26.21 |
| Treatment C1 | Palatability Score | Sweetness: Day 1: 0 min | 72.2 millimeter (mm) | Standard Deviation 23.97 |
| Treatment C1 | Palatability Score | Acceptable to swallow:Day1:2-5min after medication | 82.5 millimeter (mm) | Standard Deviation 23.04 |
| Treatment C1 | Palatability Score | Flavor: Day 1: 0 min | 72.2 millimeter (mm) | Standard Deviation 27.17 |
| Treatment C1 | Palatability Score | Taste in Mouth: Day 1:2-5 minutes after medication | 68.9 millimeter (mm) | Standard Deviation 27.77 |
| Treatment C1 | Palatability Score | Smell: Day 1: 0 min | 64.8 millimeter (mm) | Standard Deviation 25.22 |
| Treatment C2 | Palatability Score | Flavor: Day 1: 0 min | 68.8 millimeter (mm) | Standard Deviation 22.33 |
| Treatment C2 | Palatability Score | Acceptable to swallow:Day1:2-5min after medication | 68.7 millimeter (mm) | Standard Deviation 21.28 |
| Treatment C2 | Palatability Score | Overall liking of Medicine: Day 1: 0 min | 68.0 millimeter (mm) | Standard Deviation 20.47 |
| Treatment C2 | Palatability Score | Taste in Mouth: Day 1:2-5 minutes after medication | 47.1 millimeter (mm) | Standard Deviation 28.29 |
| Treatment C2 | Palatability Score | Sweetness: Day 1: 0 min | 73.0 millimeter (mm) | Standard Deviation 19.31 |
| Treatment C2 | Palatability Score | Smell: Day 1: 0 min | 61.9 millimeter (mm) | Standard Deviation 21.64 |
| Treatment D | Palatability Score | Taste in Mouth: Day 1:2-5 minutes after medication | 47.7 millimeter (mm) | Standard Deviation 26.82 |
| Treatment D | Palatability Score | Acceptable to swallow:Day1:2-5min after medication | 70.0 millimeter (mm) | Standard Deviation 19.5 |
| Treatment D | Palatability Score | Smell: Day 1: 0 min | 64.6 millimeter (mm) | Standard Deviation 19.67 |
| Treatment D | Palatability Score | Sweetness: Day 1: 0 min | 68.0 millimeter (mm) | Standard Deviation 22.12 |
| Treatment D | Palatability Score | Overall liking of Medicine: Day 1: 0 min | 63.3 millimeter (mm) | Standard Deviation 23.86 |
| Treatment D | Palatability Score | Flavor: Day 1: 0 min | 65.9 millimeter (mm) | Standard Deviation 22.95 |
| Treatment E | Palatability Score | Acceptable to swallow:Day1:2-5min after medication | 38.1 millimeter (mm) | Standard Deviation 29.9 |
| Treatment E | Palatability Score | Flavor: Day 1: 0 min | 32.9 millimeter (mm) | Standard Deviation 29.1 |
| Treatment E | Palatability Score | Smell: Day 1: 0 min | 46.9 millimeter (mm) | Standard Deviation 26.17 |
| Treatment E | Palatability Score | Sweetness: Day 1: 0 min | 40.8 millimeter (mm) | Standard Deviation 30.59 |
| Treatment E | Palatability Score | Overall liking of Medicine: Day 1: 0 min | 53.2 millimeter (mm) | Standard Deviation 26.1 |
| Treatment E | Palatability Score | Taste in Mouth: Day 1:2-5 minutes after medication | 29.5 millimeter (mm) | Standard Deviation 26.12 |
Secondary
Relative Bioavailability (Frel) of L-Praziquantel (L-PZQ)
Relative bioavailability (Frel) was calculated for L-PZQ only (treatment A versus treatment B) using the formula: Frel = (AUC0-inf (test or Treatment A)/AUC0-inf (reference or treatment B)) multiplied by 100.
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: The PK population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Treatment A | Relative Bioavailability (Frel) of L-Praziquantel (L-PZQ) | 40.075 Percentage bioavailability |
Secondary
Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ)
Time prior to the first measurable (non-zero) concentration (tlag) of drug L-PZQ
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: The pharmacokinetic (PK) population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) | 0.0 hour |
| Treatment B | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) | 0.0 hour |
| Treatment C1 | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) | 0.0 hour |
| Treatment C2 | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) | 0.0 hour |
| Treatment D | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) | 0.0 hour |
| Treatment E | Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) | 0.0 hour |
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ)
Time frame: Pre-dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 12.0, 16 and 24 hours post-dose
Population: The pharmacokinetic (PK) population included all randomized subjects who were treated according to the protocol without relevant protocol violations with respect to factors likely to affect the comparability of PK results and the availability of the primary target variable AUC0-inf for MSC2499550A in periods 1 and 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A | Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | 2.500 hour |
| Treatment B | Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | 2.500 hour |
| Treatment C1 | Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | 2.250 hour |
| Treatment C2 | Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | 3.000 hour |
| Treatment D | Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | 2.000 hour |
| Treatment E | Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | 4.000 hour |