Relative Bioavailability Trial of L-Praziquantel in Healthy Volunteers

NCT02271984 | Completed Phase 1 Results

• 1 other identifier: 200661-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy; Praziquantel; L-PZQ; PZQ; MSC2499550A; Bioavailability; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (13)

• 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)

  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

• 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

• 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

Study Arms (5)

Treatment A: MSC2499550A

EXPERIMENTAL

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

Drug: MSC2499550A

Treatment B: Cysticide

EXPERIMENTAL

Cysticide® 40 mg/kg under fed condition

Drug: Cysticide

Treatment C: MSC2499550A

EXPERIMENTAL

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

Drug: MSC2499550A

Treatment D: MSC2499550A

EXPERIMENTAL

MSC2499550A 20 mg/kg under fasting condition

Drug: MSC2499550A

Treatment E: MSC2499550A

EXPERIMENTAL

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

Drug: MSC2499550A

Interventions

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.

Also known as: L-PZQ

Treatment A: MSC2499550A

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.

Also known as: Praziquantel

Treatment B: Cysticide

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Please contact the Merck KGaA Communication Center

Darmstadt, Germany

Location

Related Publications (1)

• 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.

  PMID: 30536632 DERIVED

MeSH Terms

Interventions

Praziquantel

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: October 22, 2014
• Study Start: October 31, 2014
• Primary Completion: December 31, 2014
• Study Completion: December 31, 2014
• Last Updated: January 3, 2018
• Results First Posted: January 3, 2018

Record last verified: 2017-05

Locations

DE (1)