Clinical trial NCT02271984: Relative Bioavailability Trial of L-Praziquantel in Healthy Volunteers
Official title: A Phase I, Open-Label, Randomized, Single Dose, Five Period, Crossover, Single Center Trial To Assess The Relative Bioavailability Of The 150 mg ODT Formulation Of L PZQ (MSC2499550A) Versus The Current 500 mg PZQ Commercial Racemate Tablet Formulation In Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy
Praziquantel
L-PZQ
PZQ
MSC2499550A
Bioavailability
Pharmacokinetics
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2014-10-22
Enrollment: 36
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, 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment
timeFrame: 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
Secondary outcomes:
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ)
timeFrame: 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: Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ)
timeFrame: 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: 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
timeFrame: 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: 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)
timeFrame: 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: Maximum Observed Concentration in Plasma (Cmax) of L-Praziquantel (L-PZQ) After Dose Adjustment
timeFrame: 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: Apparent Terminal Half-life (T1/2) of L-Praziquantel (L-PZQ)
timeFrame: 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: Relative Bioavailability (Frel) of L-Praziquantel (L-PZQ)
timeFrame: 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: Apparent Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ)
timeFrame: 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: Apparent Total Body Clearance of Drug From Plasma (CL/f) of L-Praziquantel (L-PZQ)
timeFrame: 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: Apparent Volume of Distribution During the Terminal Phase (Vz/f) of L-Praziquantel (L-PZQ)
timeFrame: 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: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
timeFrame: 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)
measure: Palatability Score
timeFrame: 0 min for flavor, smell, sweetness, overall liking; 2-5 minutes post dose for taste in mouth and acceptability on Day 1
measure: Number of Subjects With Clinical Significant Laboratory Abnormalities, Electrocardiogram (ECG), Physical Examination and Vital Signs Reported as Treatment Emergent Adverse Events
timeFrame: 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)
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:
citation: 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.