A Crossover Study to Assess the Effect of Intravenous Infusion of Piperacillin/Tazobactam on the Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) in Healthy Adult Participants

Healthy Clinical Trial

Official title:

A Phase 1, Open-label, Randomized, 2-period, Crossover Study to Assess the Effect of Intravenous Infusion of Piperacillin/Tazobactam on the Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03441529
• Other study ID #: CR108431
• Secondary ID: 2017-004504-2264
• Status: Completed
• Phase: Phase 1
• Start date: February 9, 2018
• Est. completion date: May 3, 2018

Study information

• Verified date: June 2018
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the effect of intravenous (IV) infusions of piperacillin/tazobactam on the pharmacokinetics (PK) of JNJ-63549109 after a single oral dose of lumicitabine in healthy adult participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 3, 2018
• Est. primary completion date: May 3, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Participant must have a body mass index (BMI); weight in kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per square meter (kg/m^2), extremes included, and a body weight not less than 50.0 kg, inclusive, at screening

• Participant must have a blood pressure between 90 and 140 millimeter of mercury (mmHg) systolic, extremes included, and no higher than 90 mmHg diastolic. If blood pressure is out of range, 1 repeated assessment is permitted after an additional 5 minutes of rest

• Participants must have normal values for alanine transaminase (ALT) and aspartate aminotransferase (AST) (less than or equal to [<=] 1.0*upper limit of laboratory normal range [ULN])

• Participant must have a normal renal function (estimated glomerular filtration rate [eGFR] greater than or equal to [>=] 90 milliliter per minute per 1.73 square meter [mL/min/1.73m^2]) determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)

• A female Participant, except if postmenopausal, must have a negative serum beta human chorionic gonadotropin (beta hCG) pregnancy test at screening, and a negative urine beta hCG pregnancy test on Day 1 of each treatment period

• Participant must be healthy on the basis of medical history, physical examination, 12 lead electrocardiogram (ECG), vital signs, and laboratory tests performed at screening

Exclusion Criteria:

• Participant has a history of current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease (example, glucose 6 phosphate dehydrogenase deficiency), coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, seizure disorders, or any other illness, that in the investigator's and/or sponsor's medical monitor opinion should exclude the participant or that could interfere with the interpretation of the study results

• Participant has a history of human immunodeficiency virus type 1 (HIV-1) or type 2 (HIV-2) antibody positive, or tests positive for HIV-1 or -2 at screening

• Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well being) or that could prevent, limit, or confound the protocol specified assessments

• Participants with a history of allergic reactions to any of the penicillins, cephalosporins, monobactams, carbapenems, or beta lactamase inhibitors (clavulanate, sulbactam, tazobactam, avibactam), or other contra indications for the use of piperacillin/tazobactam

• Participant with a history of clinically significant drug allergy such as, but not limited to, sulfonamides, or drug allergy diagnosed in previous studies with experimental drugs

• Participant has known allergies, hypersensitivity, or intolerance to lumicitabine or its excipients

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Lumicitabine
Participants will receive single oral dose of 1000 mg lumicitabine as per assigned treatment sequence.
• Piperacillin/Tazobactam
Participants will receive three IV infusions of piperacillin/tazobactam combination product (4 g of piperacillin and 0.5 g of tazobactam) every 6 hours on Day 1.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of JNJ-64041575)	Cmax is the maximum observed plasma concentration.	Predose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Primary	Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-63549109 (Metabolite of JNJ-64041575)	Area under the plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit [non BQL]) concentration, calculated by linear trapezoidal summation.	Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Primary	Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-63549109 (Metabolite of JNJ-64041575)	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/ lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.	Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-63549109 (Metabolite of JNJ- 64041575)	Tmax is the actual sampling time to reach maximum observed plasma concentration.	Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Primary	Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ-63549109 (Metabolite of JNJ- 64041575)	C12h is observed plasma concentration at 12 hours post dose.	12 hours postdose
Primary	Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ-63549109 (Metabolite of JNJ- 64041575)	C24h is observed plasma concentration at 24 hours post dose.	24 hours postdose
Primary	Elimination Rate Constant (Lambda[z]) of JNJ-63549109 (Metabolite of JNJ- 64041575)	Lambda[z] is the apparent terminal elimination rate constant, estimated by linear regression using the terminal logarithmic (log)-linear phase of the log-transformed concentration vs time data.	Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Primary	Elimination Half-Life (T1/2) of JNJ-63549109 (Metabolite of JNJ- 64041575)	T1/2 is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).	Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Secondary	Maximum Observed Plasma Concentration (Cmax) of JNJ-64167896 (Metabolite of JNJ-64041575)	Cmax is the maximum observed plasma concentration.	Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Secondary	Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-64167896 (Metabolite of JNJ-64041575)	Area under the plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit [non BQL]) concentration, calculated by linear trapezoidal summation.	Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Secondary	Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64167896 (Metabolite of JNJ-64041575)	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/ lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.	Predose, 15 min, 30 min, 1h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Secondary	Number of Participants With Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to end of study (approximately 2 months)
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ 64167896 (Metabolite of JNJ-64041575)	Tmax is the actual sampling time to reach maximum observed plasma concentration.	Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Secondary	Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ 64167896 (Metabolite of JNJ-64041575)	C12h is observed plasma concentration at 12 hours post dose.	12 hours postdose
Secondary	Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ 64167896 (Metabolite of JNJ-64041575)	C24h is observed plasma concentration at 24 hours post dose.	24 hours postdose
Secondary	Elimination Rate Constant (Lambda[z]) of JNJ 64167896 (Metabolite of JNJ-64041575)	Lambda[z] is the apparent terminal elimination rate constant, estimated by linear regression using the terminal logarithmic (log)-linear phase of the log-transformed concentration vs time data.	Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)
Secondary	Elimination Half-Life (T1/2) of JNJ 64167896 (Metabolite of JNJ-64041575)	T1/2 is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).	Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 hours and end of study (16 days after last study drug intake or early withdrawal) (approximately 2 months)