Clinical trial NCT03437447: Praziquantel Bioequivalence Study
Official title: A Phase I, Open-label, Randomized, Three-period, Crossover, Partial Replicated, Reference-scaled, Single Center Trial to Assess the Bioequivalence of a Single Oral Dose of 1200 mg of the New Cisticid 600 mg Tablet Formulation Versus Comparator Biltricide in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Bioavailability
Bioequivalence
Praziquantel
Cysticide
Pharmacokinetics
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-02-19
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

* 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
* Other protocol defined inclusion criteria could apply

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 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
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ)
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ)
timeFrame: 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:
measure: Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ)
timeFrame: 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
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline up to Day 29
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: Baseline up to Day 29
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs
timeFrame: Baseline up to Day 29
measure: Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
timeFrame: Baseline up to Day 29
Other outcomes:
Locations:
city: México
country: Mexico
facility: Clínica de Enfermedades Crónicas y de Procedimientos Especiales, Sociedad Civil (SC)
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: