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CompletedNCT03441529Updated Jun 7, 2018

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

A Phase 1 interventional study of Lumicitabine and Piperacillin/Tazobactam in Healthy, sponsored by Janssen Research & Development, LLC. Completed at 1 site in Belgium. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-06-07.

Sponsored by Janssen Research & Development, LLC · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
18
Allocation
Randomized
Ages
18 Years to 60 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Healthy
03

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
04

Study design

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

Study arms

  • 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 · Drug: Piperacillin/Tazobactam

  • 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 · Drug: Piperacillin/Tazobactam

Interventions

  • DrugLumicitabine

    Participants will receive single oral dose of 1000 mg lumicitabine as per assigned treatment sequence.

    Also known as: JNJ-64041575, ALS-008176

  • DrugPiperacillin/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.

05

What researchers measure

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of JNJ-64041575)

    Cmax is the maximum observed plasma concentration.

    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)

  2. 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.

    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)

  3. 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.

    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)

  4. 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.

    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)

  5. 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.

    Time frame: 12 hours postdose

  6. 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.

    Time frame: 24 hours postdose

  7. 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.

    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)

  8. 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).

    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)

Secondary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of JNJ-64167896 (Metabolite of JNJ-64041575)

    Cmax is the maximum observed plasma concentration.

    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)

  2. 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.

    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)

  3. 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.

    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)

  4. 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.

    Time frame: Up to end of study (approximately 2 months)

  5. 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.

    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)

  6. 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.

    Time frame: 12 hours postdose

  7. 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.

    Time frame: 24 hours postdose

  8. 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.

    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)

  9. 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).

    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)

06

Study locations

1 site
  • Clinical Pharmacology Unit
    Merksem, 2170, Belgium
07

Registry details

Key details

Study ID
NCT03441529
Lead sponsor
Janssen Research & Development, LLC
Responsible party
Sponsor
First posted
Feb 22, 2018
Start date
Feb 9, 2018
Primary completion
May 3, 2018
Completion
May 3, 2018
Last update
Jun 7, 2018

Study contacts

Janssen Research & Development, LLC Clinical Trial
study director · Janssen Research & Development, LLC

Oversight

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