A Phase I, Open-label, Randomized, Four-period, Crossover, Single Center Trial to Assess the Relative Bioavailability of a Single Oral Dose of the New 150 mg Oral Dispersible Tablet (ODT) Formulation of Praziquantel (PZQ), MSC1028703A, at Different Dose Levels vs the Current Commercial 500 mg Tablet Formulation of PZQ in Healthy Male Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Oral dispersible tablet of praziquantel (ODT-PZQ)
- Conditions
- Healthy
- Sponsor
- Merck KGaA, Darmstadt, Germany
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a phase I, open-label, randomized, 4 period, crossover, single-center trial. The purpose of this trial is to assess the relative bio-availability of racemate Oral Dispersible Tablet praziquantel (ODT-PQZ) (MSC1028703A) 150 milligram (mg) versus the current marketed praziquantel (PZQ) (Cysticide® 500 mg) formulation in healthy male volunteers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy males 18-55 years of age (inclusive at screening)
- •Male subjects with partners of childbearing potential must have had a vasectomy or use acceptable methods of birth control (that is, condoms) and not donate sperm during, and until 90 days after the last dose of the trial medication
- •Provide written informed consent prior to any trial related procedure
- •Body weight of greater than or equal to (\>=)55.0 kg to less than (\<) 95.0 kg and a body mass index (BMI) between 18.5 and 29.9 kilogram per square meter (kg/m\^2)
- •Able to communicate well with the Investigator, understand the protocol requirements and restrictions, and willing to comply with the requirements of the entire trial
- •Non-smoker (= 0 cigarettes, pipes, cigars or other) from at least 3 months prior to start of trial
- •Electrocardiogram (ECG) recording (12-lead) without signs of clinically relevant pathology, in particular QTcB \< 450 milliseconds (ms)
- •Vital signs (systolic blood pressure, diastolic blood pressure and pulse) in supine position are within the normal range or show no clinically relevant deviation as judged by the Investigator
Exclusion Criteria
- •Any surgical or medical condition, including findings in the medical history or in the pre-study assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the subject in the trial or that could interfere with the trial objectives, conduct or evaluation
- •History of gastrointestinal (GI) tract surgery, other GI tract diseases or acute GI tract infections within the last 2 weeks that could influence the GI absorption and/or motility according to the Investigator's opinion
- •Any clinically relevant abnormality in the safety laboratory parameters as judged by the Investigator
- •Positive results from serology examination for Hepatitis B surface antigen (HBsAg), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV)
- •Have an ascertained or presumptive contraindication or hypersensitivity to the active drug substance and/or formulations' ingredients
- •Have any clinically significant history of allergic conditions which the Investigator considers may affect the outcome of the trial
- •History or presence of drug abuse or alcohol abuse (as defined by the assessment of the investigator) at screening and on each admission
- •Blood donation or loss of more than 400 mL of blood within 3 months before the first administration of the investigational product
- •Administration of any investigational product or use of any investigational device within 60 days prior to first dosing that may affect the pharmacokinetics of the investigational product
- •Subjects who have used drugs that may affect the pharmacokinetics (PK) of PZQ from 15 days before the first administration of the investigational product until the last PK sample
Arms & Interventions
Sequence A-B-C1-D1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-C1-D1
Intervention: Cysticide
Sequence A-B-C1-D1
Intervention: ODT-PZQ
Sequence A-B-C1-D2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-C1-D2
Intervention: Cysticide
Sequence A-B-C1-D2
Intervention: ODT-PZQ
Sequence A-B-C2-D1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-C2-D1
Intervention: Cysticide
Sequence A-B-C2-D1
Intervention: ODT-PZQ
Sequence A-B-C2-D2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-C2-D2
Intervention: Cysticide
Sequence A-B-C2-D2
Intervention: ODT-PZQ
Sequence A-B-D1-C1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-D1-C1
Intervention: Cysticide
Sequence A-B-D1-C1
Intervention: ODT-PZQ
Sequence A-B-D2-C1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-D2-C1
Intervention: Cysticide
Sequence A-B-D2-C1
Intervention: ODT-PZQ
Sequence A-B-D1-C2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-D1-C2
Intervention: Cysticide
Sequence A-B-D1-C2
Intervention: ODT-PZQ
Sequence A-B-D2-C2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence A-B-D2-C2
Intervention: Cysticide
Sequence A-B-D2-C2
Intervention: ODT-PZQ
Sequence B-A-C1-D1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-C1-D1
Intervention: Cysticide
Sequence B-A-C1-D1
Intervention: ODT-PZQ
Sequence B-A-C1-D2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-C1-D2
Intervention: Cysticide
Sequence B-A-C1-D2
Intervention: ODT-PZQ
Sequence B-A-C2-D1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-C2-D1
Intervention: Cysticide
Sequence B-A-C2-D2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-C2-D1
Intervention: ODT-PZQ
Sequence B-A-C2-D2
Intervention: Cysticide
Sequence B-A-C2-D2
Intervention: ODT-PZQ
Sequence B-A-D1-C1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-D1-C1
Intervention: Cysticide
Sequence B-A-D1-C1
Intervention: ODT-PZQ
Sequence B-A-D2-C1
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-D2-C1
Intervention: Cysticide
Sequence B-A-D2-C1
Intervention: ODT-PZQ
Sequence B-A-D1-C2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-D1-C2
Intervention: Cysticide
Sequence B-A-D1-C2
Intervention: ODT-PZQ
Sequence B-A-D2-C2
Intervention: Oral dispersible tablet of praziquantel (ODT-PZQ)
Sequence B-A-D2-C2
Intervention: Cysticide
Sequence B-A-D2-C2
Intervention: ODT-PZQ
Outcomes
Primary Outcomes
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of L-Praziquantel (L-PZQ)
Time Frame: Pre-dose,0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment
AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. AUC0-inf, adj was defined as the AUC0-inf adjusted for the actual administered dose of L-PZQ.
Secondary Outcomes
- Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- AUC From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) Adjusted for the Actual Administered Dose (AUC0-t, Adj) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Relative Bioavailability (Frel) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adjusted for the Actual Administered Dose (AUC0-inf, Adj) of D-PZQ and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ(Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16 and 24 hours post-dose on Day 1 of each treatment)
- Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation(Baseline up to end of treatment (up to Day 32))
- Palatability Assessment Based on Visual Analog Scale (VAS) Score(Immediately and 2-5 minutes (min) after dosing on Day 1 of each treatment)
- Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters(Baseline up to end of treatment (up to Day 32))