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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A: MSC2499550A | Experimental | MSC2499550A: 20 milligram per kilogram (mg/kg) under fed condition |
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| Treatment B: Cysticide | Experimental | Cysticide® 40 mg/kg under fed condition |
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| Treatment C: MSC2499550A | Experimental | C1:MSC2499550A :10 mg/kg under fed condition C2:MSC2499550A : 30 mg/kg under fed condition |
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| Treatment D: MSC2499550A | Experimental | MSC2499550A 20 mg/kg under fasting condition |
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| Treatment E: MSC2499550A | Experimental | MSC2499550A: 20 mg/kg directly disintegrated in mouth under fed condition |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MSC2499550A | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Please contact the Merck KGaA Communication Center | Darmstadt | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30536632 | Derived | Bagchus WM, Bezuidenhout D, Harrison-Moench E, Kourany-Lefoll E, Wolna P, Yalkinoglu O. Relative Bioavailability of Orally Dispersible Tablet Formulations of Levo- and Racemic Praziquantel: Two Phase I Studies. Clin Transl Sci. 2019 Jan;12(1):66-76. doi: 10.1111/cts.12601. Epub 2018 Dec 21. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | ABC1DE | Subjects received a single oral dose of MSC2499550A oral disintegrating tablet (ODT) formulation at 20 milligram per kilogram (mg/kg) dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period. |
| FG001 | ABDEC1 | Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period under fed condition followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period. |
| FG002 | ABEC1D | Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period. |
| FG003 | BAC1DE | Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period. |
| FG004 | BADEC1 | Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period. |
| FG005 | BAEC1D | Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water (C1) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period. |
| FG006 | ABC2DE | Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period. |
| FG007 | ABDEC2 | Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period. |
| FG008 | ABEC2D | Subjects received a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in first intervention period followed by single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fourth intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period. |
| FG009 | BAC2DE | Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in third intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fourth intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fifth intervention period under fed condition. There was a wash-out period of at least 7 days between each intervention period. |
| FG010 | BADEC2 | Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in third intervention period under fasted conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in fourth intervention period followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fifth intervention period under fed conditions. There was a wash-out period of at least 7 days between each intervention period. |
| FG011 | BAEC2D | Subjects received a single oral dose of current PZQ formulation (Cysticide®) at 40 mg/kg with water (B) in first intervention period followed by a single oral dose of MSC2499550A ODT formulation at 20 mg/kg dispersed in water (A) in second intervention period followed by a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth (E) in third intervention followed by a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water (C2) in fourth intervention under fed conditions followed by a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water (D) in fifth intervention period under fasted conditions. There was a wash-out period of at least 7 days between each intervention period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention Period (1 Day) |
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| Washout Period 1 (7 Days) |
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| Second Intervention Period (1 Day) |
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| Washout Period 2 (7 Days) |
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| Third Intervention Period (1 Day) |
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| Washout Period 3 (7 Days) |
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| Fourth Intervention Period (Day 1) |
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| Washout Period 4 (7 Days) |
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| Fifth Intervention Period (1 Day) |
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Safety analysis set: All subjects who received at least 1 dose of trial medication and who had follow-up safety assessments. As per Statistical Analysis Plan, Baseline Characteristics were to be reported for the overall population only. A summary by sequence or by some other grouping variable was not foreseen and thus is not available.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | 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 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A | Subjects received a single oral dose of MSC2499550A formulation at 20 milligram per kilogram (mg/kg) dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each intervention period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@merckgroup.com |
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| ID | Term |
|---|---|
| D011223 | Praziquantel |
| ID | Term |
|---|---|
| D007546 | Isoquinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Cysticide | Drug | 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. |
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| MSC2499550A | Drug | Subjects will receive a single oral dose of MSC2499550A formulation at 10 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 of the intervention period. |
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| MSC2499550A | Drug | Subjects will receive a single oral dose of MSC2499550A formulation at 30 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 of the intervention period. |
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| MSC2499550A | Drug | Subjects will receive a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted 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. |
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| MSC2499550A | Drug | Subjects will receive a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There will be a wash-out period of at least 7 days between each of the intervention period. |
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Time prior to the first measurable (non-zero) concentration (tlag) of drug 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 |
| 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. | 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 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. | 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 |
| 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) | 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. | 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) 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. | 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 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. | 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) | 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). | 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 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). | 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 |
| 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. | 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) |
| 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". | 0 min for flavor, smell, sweetness, overall liking; 2-5 minutes post dose for taste in mouth and acceptability on Day 1 |
| 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. | 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) |
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| NOT COMPLETED |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| OG001 | Treatment B | Subjects received 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 was a wash-out period of at least 7 days between each of the intervention period. |
| OG002 | Treatment C1 | Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. |
| OG003 | Treatment C2 | Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. |
| OG004 | Treatment D | Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. |
| OG005 | Treatment E | Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. |
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| Secondary | Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) | 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. | Posted | Median | Full Range | hour | 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 |
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| 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 | 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. | Posted | Median | Full Range | hour | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per milliliter (h*ng/mL) | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Percent extrapolated | 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 |
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| Secondary | Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 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 |
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| 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. | 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. | Posted | Median | Full Range | hour | 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 |
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| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | Percentage bioavailability | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | per hour (1/hour) | 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 |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | 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 |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | 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 |
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| 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. | 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. | Posted | Number | Subjects | 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) |
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| 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". | 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. | Posted | Mean | Standard Deviation | millimeter (mm) | 0 min for flavor, smell, sweetness, overall liking; 2-5 minutes post dose for taste in mouth and acceptability on Day 1 |
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| 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. | 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. | Posted | Number | Subjects | 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) |
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| 0 |
| 36 |
| 8 |
| 36 |
| EG001 | Treatment B | Subjects received 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 was a wash-out period of at least 7 days between each of the intervention period. | 0 | 36 | 17 | 36 |
| EG002 | Treatment C1 | Subjects received a single oral dose of MSC2499550A formulation at 10 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. | 0 | 18 | 4 | 18 |
| EG003 | Treatment C2 | Subjects received a single oral dose of MSC2499550A formulation at 30 mg/kg dispersed in water under fed condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. | 0 | 17 | 4 | 17 |
| EG004 | Treatment D | Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg dispersed in water in fasted condition in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. | 0 | 35 | 5 | 35 |
| EG005 | Treatment E | Subjects received a single oral dose of MSC2499550A formulation at 20 mg/kg directly disintegrated in the mouth without water under fed conditions in one of the intervention periods. There was a wash-out period of at least 7 days between each of the intervention period. | 0 | 36 | 1 | 36 |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Influenza | Infections and infestations | MedDRA Version 17.0 | Non-systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA Version 17.0 | Non-systematic Assessment |
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| Excoriation | Injury, poisoning and procedural complications | MedDRA Version 17.0 | Non-systematic Assessment |
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| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.0 | Non-systematic Assessment |
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Not provided
| Serious TEAEs |
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| TEAEs leading to discontinuation |
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| TEAEs leading to death |
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| Smell: Day 1: 0 min |
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| Sweetness: Day 1: 0 min |
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| Overall liking of Medicine: Day 1: 0 min |
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| Taste in Mouth: Day 1:2-5 minutes after medication |
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| Acceptable to swallow:Day1:2-5min after medication |
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| ECG abnormalities |
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| Vital signs abnormalities |
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| Physical signs abnormalities |
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