A Phase 1 Study to Evaluate the Effect of the Organic Anion Transporter Inhibitor Probenecid on the Pharmacokinetics of JNJ-64041575 in Healthy Adults

NCT03105986 | Completed Phase 1

• 3 other identifiers: CR10830064041575RSV10022016-003923-49
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

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

  Cmax is the maximum observed plasma concentration.

  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

• 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.

  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

• 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.

  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 (4)

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

  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

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

  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

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

  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

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  From Signing of Informed Consent Form (ICF) to End of Study (Approximately up to 88 days)

Study Arms (2)

Treatment sequence AB

EXPERIMENTAL

Participants will receive Treatment A (1000 milligram (mg) oral dose of JNJ-64041575 on Day 1) in Period 1, followed by Treatment B (1000 mg oral dose of JNJ-64041575 on Day 22 along with probenecid 500 mg on Day 21 to Day 28) in Period 2. A washout Period of 21 days will be maintained between each Period.

Drug: JNJ-64041575; Drug: Probenecid

Treatment sequence BA

EXPERIMENTAL

Participants will receive Treatment B (1000 mg oral dose of JNJ-64041575 on Day 1 along with probenecid 500 mg on Day -1 to Day 7) in Period 1, followed by Treatment A (1000 mg oral dose of JNJ-64041575 on Day 22) in Period 2. A washout Period of 21 days will be maintained between each Period.

Drug: JNJ-64041575; Drug: Probenecid

Interventions

JNJ-64041575 DRUG

Two 500-mg tablets administered as a single oral dose under fasted conditions on Day 1 or Day 22.

Treatment sequence AB; Treatment sequence BA

Probenecid DRUG

One 500-mg tablet administered as a single oral dose with a total of 30 doses (2 doses on Day -1/21 starting in the evening followed by 4 doses per day on the rest of the days).

Treatment sequence AB; Treatment sequence BA

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen-Cilag International NV: lead

Study Sites (1)

Charité Research Organisation GmbH

Berlin, 10117, Germany

Location

MeSH Terms

Interventions

Probenecid

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Janssen-Cilag International NV Clinical Trial

  Janssen-Cilag International NV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 10, 2017
• Study Start: April 5, 2017
• Primary Completion: June 16, 2017
• Study Completion: June 16, 2017
• Last Updated: August 13, 2018

Record last verified: 2018-08

Locations

DE (1)