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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

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ClinicalTrials.gov Identifier: NCT03441529
Recruitment Status : Completed
First Posted : February 22, 2018
Last Update Posted : June 7, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Lumicitabine Drug: Piperacillin/Tazobactam Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : February 9, 2018
Actual Primary Completion Date : May 3, 2018
Actual Study Completion Date : May 3, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Sequence 1 (AB)
Participants will receive Treatment A as a single oral dose of 1000 milligram (mg) lumicitabine (4*250 mg tablets) on Day 1 of period 1 followed by Treatment B as a single oral dose of 1000 mg lumicitabine (4*250 mg tablets) together with piperacillin/tazobactam administered as three 30-minute Intravenous (IV) infusions of 4.5 gram (g) piperacillin/tazobactam (4 g of piperacillin and 0.5 g of tazobactam) every 6 hours on Day 1 of period 2. A washout period of at least 21 days will be maintained between each treatment period.
Drug: Lumicitabine
Participants will receive single oral dose of 1000 mg lumicitabine as per assigned treatment sequence.
Other Name: JNJ-64041575, ALS-008176

Drug: 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.

Experimental: Treatment Sequence 2 (BA)
Participants will receive Treatment B on Day 1 of period 1 followed by Treatment A on Day 1 of period 2. A washout period of at least 21 days will be maintained between each treatment period.
Drug: Lumicitabine
Participants will receive single oral dose of 1000 mg lumicitabine as per assigned treatment sequence.
Other Name: JNJ-64041575, ALS-008176

Drug: 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.




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    Cmax is the maximum observed plasma concentration.

  2. Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-63549109 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    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.

  3. Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-63549109 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    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.

  4. Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ-63549109 (Metabolite of JNJ- 64041575) [ Time Frame: 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) ]
    Tmax is the actual sampling time to reach maximum observed plasma concentration.

  5. Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ-63549109 (Metabolite of JNJ- 64041575) [ Time Frame: 12 hours postdose ]
    C12h is observed plasma concentration at 12 hours post dose.

  6. Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ-63549109 (Metabolite of JNJ- 64041575) [ Time Frame: 24 hours postdose ]
    C24h is observed plasma concentration at 24 hours post dose.

  7. Elimination Rate Constant (Lambda[z]) of JNJ-63549109 (Metabolite of JNJ- 64041575) [ Time Frame: 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) ]
    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.

  8. Elimination Half-Life (T1/2) of JNJ-63549109 (Metabolite of JNJ- 64041575) [ Time Frame: 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) ]
    T1/2 is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).


Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of JNJ-64167896 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    Cmax is the maximum observed plasma concentration.

  2. Area Under Plasma Concentration Time Curve From Time Zero to the Last Quantifiable (AUC [0-last]) of JNJ-64167896 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    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.

  3. Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-64167896 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    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.

  4. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to end of study (approximately 2 months) ]
    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.

  5. Time to Reach Maximum Observed Plasma Concentration (Tmax) of JNJ 64167896 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    Tmax is the actual sampling time to reach maximum observed plasma concentration.

  6. Observed Plasma Concentration at 12 Hours Post dose (C12h) of JNJ 64167896 (Metabolite of JNJ-64041575) [ Time Frame: 12 hours postdose ]
    C12h is observed plasma concentration at 12 hours post dose.

  7. Observed Plasma Concentration at 24 Hours Post dose (C24h) of JNJ 64167896 (Metabolite of JNJ-64041575) [ Time Frame: 24 hours postdose ]
    C24h is observed plasma concentration at 24 hours post dose.

  8. Elimination Rate Constant (Lambda[z]) of JNJ 64167896 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    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.

  9. Elimination Half-Life (T1/2) of JNJ 64167896 (Metabolite of JNJ-64041575) [ Time Frame: 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) ]
    T1/2 is the apparent terminal elimination half-life, calculated as 0.693/Lambda(z).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03441529


Locations
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Belgium
Clinical Pharmacology Unit
Merksem, Belgium, 2170
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03441529    
Other Study ID Numbers: CR108431
2017-004504-22 ( EudraCT Number )
64041575RSV1009 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: June 7, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Tazobactam
Piperacillin
Piperacillin, Tazobactam Drug Combination
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action