Clinical Trials/NCT02271984

NCT02271984

Completed

Phase 1

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

Merck KGaA, Darmstadt, Germany1 site in 1 country36 target enrollmentOctober 31, 2014

ConditionsHealthy

InterventionsMSC2499550A Cysticide

DrugsMSC2499550A Cysticide

Overview

Phase: Phase 1
Intervention: MSC2499550A
Conditions: Healthy
Sponsor: Merck KGaA, Darmstadt, Germany
Enrollment: 36
Locations: 1
Primary Endpoint: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj of L-Praziquantel (L-PZQ) After Dose Adjustment
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 31, 2014

End Date

December 31, 2014

Last Updated

8 years ago

Study Type

Interventional

Study Design

Crossover

Sex

Male

Investigators

Sponsor

Merck KGaA, Darmstadt, Germany

Responsible Party

Sponsor

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

Arms & Interventions

Treatment A: MSC2499550A

MSC2499550A: 20 milligram per kilogram (mg/kg) under fed condition

Intervention: MSC2499550A

Treatment B: Cysticide

Cysticide® 40 mg/kg under fed condition

Intervention: Cysticide

Treatment C: MSC2499550A

C1:MSC2499550A :10 mg/kg under fed condition C2:MSC2499550A : 30 mg/kg under fed condition

Intervention: MSC2499550A

Treatment D: MSC2499550A

MSC2499550A 20 mg/kg under fasting condition

Intervention: MSC2499550A

Treatment E: MSC2499550A

MSC2499550A: 20 mg/kg directly disintegrated in mouth under fed condition

Intervention: MSC2499550A

Outcomes

Primary Outcomes

Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-inf) Adj 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

The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

Secondary Outcomes

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)
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)
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)
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 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)
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)
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)
Palatability Score(0 min for flavor, smell, sweetness, overall liking; 2-5 minutes post dose for taste in mouth and acceptability on Day 1)
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)
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)
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)
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))
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))