Praziquantel Bioequivalence Study

NCT03437447 | Completed Phase 1 Results

• 1 other identifier: MS200585_0002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to assess the bioequivalence (BE) of new 600 milligram (mg) Cisticid tablet (Test) versus 600 mg Biltricide tablets (Reference) at a dose of 1200 mg in healthy male participants. Praziquantel (PZQ) is the active ingredient for Cisticid and Biltricide tablets.

Conditions

Healthy

Keywords

Bioavailability; Bioequivalence; Praziquantel; Cysticide; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ)

  Area under the plasma concentration-time curve from 0 to the time of the last quantifiable concentration.

  Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12.0 hours post-dose

• Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ)

  The maximum observed plasma concentration of L-Praziquantel (L-PZQ).

  Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12.0 hours post-dose

Secondary Outcomes (14)

• Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

  Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12.0 hours post-dose

• Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

  Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12.0 hours post-dose

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

  Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12.0 hours post-dose

• Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

  Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12.0 hours post-dose

• Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

  Pre-dose, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 8.0, 9.0, 10.0 and 12.0 hours post-dose

Study Arms (3)

First Cisticid, Then Biltricide, Then Biltricide

EXPERIMENTAL

Cisticid (Test) in Treatment Period 1 followed by Biltricide (Reference) in Treatment Period 2 and Treatment Period 3. A washout period of 7 days will be maintained between 3 treatment periods.

Drug: Cisticid; Drug: Biltricide

First Biltricide, Then Cisticid, Then Biltricide

EXPERIMENTAL

Biltricide (Reference) in Treatment Period 1 followed by Cisticid (Test) in Treatment Period 2 and then Biltricide (Reference) in Treatment Period 3. A washout period of 7 days will be maintained between 3 treatment periods.

Drug: Cisticid; Drug: Biltricide

First Biltricide, Then Biltricide, Then Cisticid

EXPERIMENTAL

Biltricide (Reference) in Treatment Period 1 and Treatment Period 2 followed by Cisticid (Test) in Treatment Period 3. A washout period of 7 days will be maintained between 3 treatment periods.

Drug: Cisticid; Drug: Biltricide

Interventions

Cisticid DRUG

Participants received single oral dose of 1200 mg (two 600 mg tablets) Cisticid (Test) on Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2) or Day 15 (Treatment Period 3).

Also known as: Praziquantel

First Biltricide, Then Biltricide, Then Cisticid; First Biltricide, Then Cisticid, Then Biltricide; First Cisticid, Then Biltricide, Then Biltricide

Biltricide DRUG

Participants received 600 mg of Biltricide (Reference) tablet at a dose of 1200 mg on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).

Also known as: Praziquantel

First Biltricide, Then Biltricide, Then Cisticid; First Biltricide, Then Cisticid, Then Biltricide; First Cisticid, Then Biltricide, Then Biltricide

Eligibility Criteria

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

You may qualify if:

• A male participant must agree to use and to have their female partners willing to use additional non-hormonal contraception (for example, condoms or occlusive cap with spermicide, non-hormonal intra-uterine device \[IUD\], previous sterilization of participant or his partner, being sexually inactive) from Day of randomization up to final end of treatment (EOT) visit
• Gave written informed consent prior to any trial related procedure
• Have a body weight (BW) of greater than (\>) 55.0 kilogram (kg) to less than (\<) 95 kg and a body mass index (BMI) between 18.0 and 27.0 kg/meter square (m\^2)
• 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 three months
• Electrocardiogram recording (12-lead) without signs of clinically relevant pathology in particular heart-rate corrected \[QTc\] (Bazett) \<450 milliseconds (ms)
• Vital signs should be in normal range (systolic blood pressure: 90 to 140 millimeters of mercury \[mmHg\]; diastolic blood pressure: 50 to 90 mmHg; pulse rate: 45 to 90 beats per minute \[bpm\]; oral body temperature between 35.0 degree centigrade \[°C\] to 37.5°C)
• All values for biochemistry, liver function test and hematology tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the Investigator. Hematocrit and hemoglobin must be above the lower limit; upper limit may range up to 15 percent (%). Remaining results, including white blood cells may range +/- 15%, if participant is asymptomatic
• Negative screen for alcohol and drugs of abuse (opiate class, barbiturates, cocaine and metabolites, amphetamines, cannabinoids, benzodiazepines and tricyclic antidepressants) at screening and on each admission
• Negative screen for Hepatitis B surface (HBs) antigens, Hepatitis C Virus (HCV) antibodies, Hepatitis A Virus (HAV) antibodies and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies

You may not qualify if:

• 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 participant in the study or that could interfere with the study objectives, conduct or evaluation
• History of surgery of the gastrointestinal (GI) tract, history of other GI tract diseases, or acute GI tract infections in the last 2 weeks, which could influence the gastrointestinal 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 (HBs) antigen, 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 (opiate class, barbiturates, cocaine and its main metabolite, amphetamines, cannabinoids, benzodiazepines and tricyclic antidepressants) or alcohol abuse at screening and on each admission. Alcohol abuse is defined by the assessment of 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 in any clinical study within 30 days prior to first PZQ administration. Participants who have used drugs that may affect the pharmacokinetics of PZQ from 14 days before dosing until the last pharmacokinetic (PK) sample, for example, phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, oral ketoconazole
• Consumption of substances known to be potent inhibitors or inducers of Cytochrome P450s (CYP P450s) such as grapefruit, orange, cranberry or juices of these fruits, herbal remedies or dietary supplements containing St. John's Wort, poppy seeds, cruciferic vegetables, in the two weeks before dosing until last PK sample
• 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 or non-compliance with the study breakfast (for example, vegetarians, vegans and participants 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
• Participant 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 participants (for example, persons kept in detention)
• Legal incapacity or limited legal capacity

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Clínica de Enfermedades Crónicas y de Procedimientos Especiales, Sociedad Civil (SC)

México, 58249, Mexico

Location

MeSH Terms

Interventions

Praziquantel

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 19, 2018
• Study Start: June 18, 2018
• Primary Completion: July 6, 2018
• Study Completion: July 6, 2018
• Last Updated: September 18, 2019
• Results First Posted: September 18, 2019

Record last verified: 2019-09

Locations

ME (1)