Clinical trial NCT02325713: Relative Bioavailability Trial of Oral Dispersible Praziquantel Tablets in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ODT-PZQ
Bio-availability
Praziquantel
Cysticide
Pharmacokinetics
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2014-12-25
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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
* Consumption of substances known to be potent inhibitors or inducers of cytochrome P450s (CYPs) within 2 weeks before the first administration of the investigational product
* Unlikely to comply with the protocol requirements, instructions and trial-related restrictions
* Non-acceptance of the study breakfast
* Excessive consumption of beverages containing xanthine (greater than \[\>\] 5 cups of coffee a day or equivalent) and the inability to refrain from the use of caffeine-containing beverages from 48 hours before the first administration of the investigational product until discharge from the clinic
* Subject is the Investigator or any Sub-Investigator, research assistant, pharmacist, trial coordinator, other staff or relative thereof directly involved in the conduct of the trial
* Vulnerable subjects
* Legal incapacity or limited legal capacity

Primary outcomes:
measure: 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)
timeFrame: 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
Secondary outcomes:
measure: Maximum Observed Concentration in Plasma (Cmax) Adjusted for the Actual Administered Dose (Cmax, Adj) of L-PZQ, D-PZQ and Racemate PZQ
timeFrame: 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
measure: Time to Reach Maximum Plasma Concentration (Tmax) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: Apparent Terminal Half-life (t1/2) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: 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
timeFrame: 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
measure: Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: Apparent Terminal Elimination Rate Constant (λz) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: Relative Bioavailability (Frel) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-PZQ, D-PZQ, and Racemate PZQ
timeFrame: 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
measure: 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
timeFrame: 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
measure: Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation
timeFrame: Baseline up to end of treatment (up to Day 32)
measure: Palatability Assessment Based on Visual Analog Scale (VAS) Score
timeFrame: Immediately and 2-5 minutes (min) after dosing on Day 1 of each treatment
measure: Number of Subjects With Clinically Significant Change From Baseline in Vital Signs, Physical Examinations, Electrocardiogram (ECG) and Laboratory Parameters
timeFrame: Baseline up to end of treatment (up to Day 32)
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please contact the Merck KGaA Communication Center
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: