CompletedNCT03437447Updated Sep 18, 2019Results posted

Praziquantel Bioequivalence Study

A Phase 1 interventional study of Cisticid and Biltricide in Healthy, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 1 site in Mexico. Open to male participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-09-18.

Sponsored by Merck KGaA, Darmstadt, Germany · Phase 1, Interventional, and Other

Phase: Phase 1
Study type: Interventional
Enrollment: 60
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: Male

Study 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 studied

Healthy

Keywords

Bioavailability
Bioequivalence
Praziquantel
Cysticide
Pharmacokinetics

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: Male
Accepts healthy volunteers: Yes

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

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

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 60 participants (actual)

Study arms

Experimental
First Cisticid, Then Biltricide, Then Biltricide
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
Experimental
First Biltricide, Then Cisticid, Then Biltricide
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
Experimental
First Biltricide, Then Biltricide, Then Cisticid
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

DrugCisticid
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
DrugBiltricide
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

What researchers measure

Primary outcomes

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.
Time frame: 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).
Time frame: 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

Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Time of the maximum drug concentration.
Time frame: 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)
Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration.
Time frame: 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)
AUC0-inf is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Time frame: 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)
AUCextra was reported in terms of percentage of AUC0-inf.
Time frame: 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)
Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.
Time frame: 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 Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Lambda Z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
Time frame: 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
Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: 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
Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd/f after oral dose was influenced by the fraction absorbed.
Time frame: 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 Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ)
Area under the drug plasma concentration-time curve from time zero to the time last measurable concentration.
Time frame: 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 Racemate PZQ (Rac-PZQ)
The maximum observed plasma concentration of rac-Praziquantel (rac-PZQ).
Time frame: 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
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time frame: Baseline up to Day 29
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Number of participants with clinically significant abnormalities in laboratory parameters were reported. Laboratory investigation included hematology, biochemistry, urinalysis and coagulation.
Time frame: Baseline up to Day 29
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Number of participants with clinically significant abnormalities in vital signs were reported. Vital signs included body temperature, systolic / diastolic blood pressure, and pulse rate.
Time frame: Baseline up to Day 29
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
Number of participants with clinically significant abnormalities in 12-lead electrocardiogram (ECG) were reported. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position.
Time frame: Baseline up to Day 29

Results

Posted Sep 18, 2019

Participant flow

Treatment Period 1

Participant flow — Treatment Period 1
Milestone	First Cisticid, Then Biltricide, Then Biltricide	First Biltricide, Then Cisticid, Then Biltricide	First Biltricide, Then Biltricide, Then Cisticid
Started	20	20	20
Completed	20	20	19
Not completed	0	0	1
Withdrew: Withdrawal by subject	0	0	1

Treatment Period 2

Participant flow — Treatment Period 2
Milestone	First Cisticid, Then Biltricide, Then Biltricide	First Biltricide, Then Cisticid, Then Biltricide	First Biltricide, Then Biltricide, Then Cisticid
Started	20	20	19
Completed	20	20	19
Not completed	0	0	0

Treatment Period 3

Participant flow — Treatment Period 3
Milestone	First Cisticid, Then Biltricide, Then Biltricide	First Biltricide, Then Cisticid, Then Biltricide	First Biltricide, Then Biltricide, Then Cisticid
Started	20	20	19
Completed	20	20	19
Not completed	0	0	0

Outcome measures

PrimaryArea 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.

Time frame:: 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
Reported as:: Mean · Hour*nanogram per milliliter (h*ng/ml)

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ)
Hournanogram per milliliter (hng/ml)	Cisticid	Biltricide First Administration	Biltricide Second Administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of L-Praziquantel (L-PZQ)	441.53 ± 345.70	547.41 ± 384.82	460.25 ± 343.37

PrimaryMaximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ)

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

Time frame:: 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
Reported as:: Mean · ng/mL

Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ)
ng/mL	Cisticid	Biltricide First Administration	Biltricide Second Administration
Maximum Observed Plasma Concentration (Cmax) of L-Praziquantel (L-PZQ)	310.87 ± 249.02	426.42 ± 324.01	363.20 ± 333.50

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

Time of the maximum drug concentration.

Time frame:: 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
Reported as:: Median · hours

Time to Reach Maximum Plasma Concentration (Tmax) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
hours	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	2.5 (1.5 to 5.5)	2 (1 to 3.5)	2.5 (1 to 4.5)
Rac-PZQ	2.5 (1.5 to 5.5)	2 (1 to 3.5)	2.5 (1 to 4.5)

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

Time prior to the first measurable (non-zero) concentration; calculated as last time point at which the concentration is less than (\<) Lower Limit of Quantification (LLOQ) before the occurrence of the first quantifiable concentration.

Time frame:: 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
Reported as:: Median · hours

Time Prior to the First Measurable (Non-zero) Concentration (Tlag) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
hours	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	1 (0.25 to 3)	1 (0.25 to 2.5)	1 (0.25 to 3.5)
Rac-PZQ	0.75 (0.00 to 2.00)	0.75 (0.25 to 2.00)	0.75 (0 to 2.5)

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

AUC0-inf is defined as the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

Time frame:: 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
Reported as:: Mean · h*ng/ml

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
h*ng/ml	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	468.52 ± 352.29	584.23 ± 410.05	497.89 ± 348.81
Rac-PZQ	2130.19 ± 1417.81	2509.42 ± 1624.33	2189.25 ± 1403.14

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

AUCextra was reported in terms of percentage of AUC0-inf.

Time frame:: 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
Reported as:: Mean · Percentage of AUC0-inf

Extrapolated Area Under the Plasma Concentration Curve From Time Tlast to Infinity (AUCextra) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Percentage of AUC0-inf	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	5.36 ± 3.73	5.49 ± 6.47	5.74 ± 4.02
Rac-PZQ	2.60 ± 1.73	2.84 ± 2.56	2.57 ± 1.56

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

Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.

Time frame:: 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
Reported as:: Mean · hours

Terminal Elimination Half-Life (t1/2) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
hours	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	1.87 ± 1.12	2.59 ± 3.01	2.32 ± 1.65
Rac-PZQ	2.19 ± 0.91	2.54 ± 1.73	2.18 ± 0.90

SecondaryTerminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

Lambda Z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

Time frame:: 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
Reported as:: Median · Per hour

Terminal Elimination Rate Constant (Lambda Z) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Per hour	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	0.452927 (0.103378 to 1.120808)	0.383267 (0.032567 to 0.721124)	0.370854 (0.073375 to 0.944209)
Rac-PZQ	0.365639 (0.135661 to 0.646499)	0.331359 (0.060282 to 0.635357)	0.370806 (0.125134 to 0.638226)

SecondaryApparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Time frame:: 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
Reported as:: Mean · Milliliter per hour

Apparent Clearance (CL/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Milliliter per hour	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	749261.50 ± 744206.88	585260.42 ± 541013.95	673193.51 ± 531848.19
Rac-PZQ	147268.6 ± 122977.13	128110.14 ± 122864.03	155851.99 ± 145104.37

SecondaryApparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vd/f after oral dose was influenced by the fraction absorbed.

Time frame:: 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
Reported as:: Mean · Milliliter

Apparent Volume of Distribution During Terminal Phase (Vd/f) of L-Praziquantel (L-PZQ) and Racemate PZQ (Rac-PZQ)
Milliliter	Cisticid	Biltricide First Administration	Biltricide Second Administration
L-PZQ	1540237.10 ± 1069504.21	1660474.33 ± 1619772.26	1800582.47 ± 1385707.17
Rac-PZQ	430368.23 ± 328721.73	385223.26 ± 279076.69	431494.33 ± 350782.53

SecondaryArea Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ)

Area under the drug plasma concentration-time curve from time zero to the time last measurable concentration.

Time frame:: 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
Reported as:: Mean · h*ng/ml

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ)
h*ng/ml	Cisticid	Biltricide First Administration	Biltricide Second Administration
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Racemate PZQ (Rac-PZQ)	2071.35 ± 1370.58	2421.73 ± 1518.94	2131.01 ± 1353.64

SecondaryMaximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ)

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

Time frame:: 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
Reported as:: Mean · ng/mL

Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ)
ng/mL	Cisticid	Biltricide First Administration	Biltricide Second Administration
Maximum Observed Plasma Concentration (Cmax) of Racemate PZQ (Rac-PZQ)	1209.15 ± 803.20	1530.23 ± 944.12	1356.18 ± 1011.46

SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs.

Time frame:: Baseline up to Day 29
Reported as:: Count of participants · Participants

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Participants	Cisticid	Biltricide First Administration	Biltricide Second Administration
Participants with TEAEs	2	5	6
Participants with Serious TEAEs	0	0	0

SecondaryNumber of Participants With Clinically Significant Abnormalities in Laboratory Parameters

Number of participants with clinically significant abnormalities in laboratory parameters were reported. Laboratory investigation included hematology, biochemistry, urinalysis and coagulation.

Time frame:: Baseline up to Day 29
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Participants	Cisticid	Biltricide First Administration	Biltricide Second Administration
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters	0	0	0

SecondaryNumber of Participants With Clinically Significant Abnormalities in Vital Signs

Number of participants with clinically significant abnormalities in vital signs were reported. Vital signs included body temperature, systolic / diastolic blood pressure, and pulse rate.

Time frame:: Baseline up to Day 29
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Abnormalities in Vital Signs
Participants	Cisticid	Biltricide First Administration	Biltricide Second Administration
Number of Participants With Clinically Significant Abnormalities in Vital Signs	0	0	0

SecondaryNumber of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings

Number of participants with clinically significant abnormalities in 12-lead electrocardiogram (ECG) were reported. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position.

Time frame:: Baseline up to Day 29
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings
Participants	Cisticid	Biltricide First Administration	Biltricide Second Administration
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings	0	0	0

Adverse events

Collected over Baseline up to Day 29. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cisticid	0/60 (0%)	0/60 (0%)	2/60 (3.3%)
Biltricide First Administration	0/60 (0%)	0/60 (0%)	5/60 (8.3%)
Biltricide Second Administration	0/60 (0%)	0/60 (0%)	6/60 (10%)

Most frequent other events

Showing 10 of 11

Most frequent other events
Event	Cisticid	Biltricide First Administration	Biltricide Second Administration
NauseaGastrointestinal disorders	0/60	0/60	2/60
AnaemiaBlood and lymphatic system disorders	0/60	2/60	0/60
Joint injuryInjury, poisoning and procedural complications	1/60	0/60	0/60
HeadacheNervous system disorders	1/60	0/60	1/60
CoughRespiratory, thoracic and mediastinal disorders	0/60	0/60	1/60
Aspartate Aminotransferase IncreasedInvestigations	0/60	0/60	1/60
Alanine Transaminase IncreasedInvestigations	0/60	0/60	1/60
Multiple injuriesInjury, poisoning and procedural complications	0/60	0/60	1/60
Head injuryInjury, poisoning and procedural complications	0/60	1/60	0/60
Abdominal painGastrointestinal disorders	0/60	1/60	0/60

Baseline characteristics

All participants who were randomized into the study.

Age, Continuous
Age, Continuous(Years)	First Cisticid, Then Biltricide, Then Biltricide	First Biltricide, Then Cisticid, Then Biltricide	First Biltricide, Then Biltricide, Then Cisticid	Total
Mean	27.80 ± 7.83	28.65 ± 7.46	27.20 ± 5.31	27.88 ± 6.86

Sex: Female, Male
Sex: Female, Male(Participants)	First Cisticid, Then Biltricide, Then Biltricide	First Biltricide, Then Cisticid, Then Biltricide	First Biltricide, Then Biltricide, Then Cisticid	Total
Female	0	0	0	0
Male	20	20	20	60

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	First Cisticid, Then Biltricide, Then Biltricide	First Biltricide, Then Cisticid, Then Biltricide	First Biltricide, Then Biltricide, Then Cisticid	Total
Hispanic or Latino	20	20	20	60
Not Hispanic or Latino	0	0	0	0
Unknown or Not Reported	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	First Cisticid, Then Biltricide, Then Biltricide	First Biltricide, Then Cisticid, Then Biltricide	First Biltricide, Then Biltricide, Then Cisticid	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	0	0
White	0	0	0	0
More than one race	20	20	20	60
Unknown or Not Reported	0	0	0	0

Study locations

1 site

Clínica de Enfermedades Crónicas y de Procedimientos Especiales, Sociedad Civil (SC)
México, 58249, Mexico

References and documents

Study documents

Study protocol · Oct 27, 2017
Statistical analysis plan · May 30, 2019

Documents are hosted by the registry — open the source record to download them.

Registry details

Key details

Study ID: NCT03437447
Lead sponsor: Merck KGaA, Darmstadt, Germany
Responsible party: Sponsor
First posted: Feb 19, 2018
Start date: Jun 18, 2018
Primary completion: Jul 6, 2018
Completion: Jul 6, 2018
Results posted: Sep 18, 2019
Last update: Sep 18, 2019

Study contacts

Medical Responsible

study director · Merck KGaA, Darmstadt, Germany

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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