Clinical trial NCT03441529: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-02-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-63549109 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-63549109 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-63549109 (Metabolite of JNJ- 64041575)
timeFrame: 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)
measure: Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ-63549109 (Metabolite of JNJ- 64041575)
timeFrame: 12 hours postdose
measure: Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ-63549109 (Metabolite of JNJ- 64041575)
timeFrame: 24 hours postdose
measure: Elimination Rate Constant (Lambda[z]) of JNJ-63549109 (Metabolite of JNJ- 64041575)
timeFrame: 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)
measure: Elimination Half-Life (T1/2) of JNJ-63549109 (Metabolite of JNJ- 64041575)
timeFrame: 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 outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-64167896 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-64167896 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64167896 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to end of study (approximately 2 months)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ 64167896 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ 64167896 (Metabolite of JNJ-64041575)
timeFrame: 12 hours postdose
measure: Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ 64167896 (Metabolite of JNJ-64041575)
timeFrame: 24 hours postdose
measure: Elimination Rate Constant (Lambda[z]) of JNJ 64167896 (Metabolite of JNJ-64041575)
timeFrame: 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)
measure: Elimination Half-Life (T1/2) of JNJ 64167896 (Metabolite of JNJ-64041575)
timeFrame: 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)
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: