Clinical trial NCT03105986: A Phase 1 Study to Evaluate the Effect of the Organic Anion Transporter Inhibitor Probenecid on the Pharmacokinetics of JNJ-64041575 in Healthy Adults
Official title: A Phase 1, Randomized, Open-label, Crossover Study to Evaluate the Effect of the Organic Anion Transporter Inhibitor Probenecid on the Pharmacokinetics of JNJ-64041575 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2017-04-10
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 purpose of this study is to evaluate the effect of multiple-dose administration of probenecid on the pharmacokinetics of JNJ-63549109 and JNJ-64167896 after a single dose of JNJ-64041575 in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

* Participants must have a body mass index (BMI; weight in \[Kilogram\] kg divided by the square of height in meters) between 18.0 and 30.0 kilogram per meter square (kg/m\^2, extremes included, and a body weight not less than 50.0 kg, inclusive, at screening
* Participant must be willing and able to adhere to the prohibitions and restrictions specified in the protocol
* Participant must have a blood pressure (after the participant is supine for 5 minutes) 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 normal \[ULN\])
* 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 pregnancy test on Day -1 and Day 21

Exclusion Criteria:

* Participant has a history of current clinically significant medical illness including cardiac arrhythmias or other cardiac disease, hematologic disease (example: glucose-6-phosphate-dehydrogenase deficiency), coagulation disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, 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
* Participants with 1 or more of the following laboratory abnormalities at screening as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table: \[1\] Serum creatinine grade 1 or greater (\>1.0 × \[Upper Limit of Normal\] ULN) \[2\] Hemoglobin grade 1 or greater (\<=10.5 grams per deciliter \[g/dL\]) \[3\] Platelet count grade 1 or greater (\<=99,999/ cubic millimeter \[mm\^3\]) \[4\] Reticulocyte count (absolute) below the lower limit of laboratory normal range \[5\] Absolute neutrophil count grade 1 or greater (\<=1,500/mm\^3) \[6\] Total bilirubin grade 1 or greater (\>1.0 × ULN) \[7\] Any other toxicity grade 2 or above, except for grade 2 elevations of low density lipoprotein cholesterol and/or cholesterol
* Participants with a history of uric acid kidney stones, conditions associated with elevated urinary uric acid excretion, participants with peptic ulcer disease or a history of peptic ulcer disease, or other contra-indications for the use of probenecid
* Participants has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
* Participants with a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of JNJ-64041575)
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose
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: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose
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: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-64167896 (Metabolite of JNJ-64041575)
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose
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: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose
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: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: From Signing of Informed Consent Form (ICF) to End of Study (Approximately up to 88 days)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: