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

• Sponsor: Janssen-Cilag International NV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03105986
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.4
• Patients Per Site Per Month: 7.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: JNJ-64041575; Drug: Probenecid	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: Apr 5, 2017
• Actual Primary Completion Date: Jun 16, 2017
• Actual Study Completion Date: Jun 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment sequence AB 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; Two 500-mg tablets administered as a single oral dose under fasted conditions on Day 1 or Day 22.; Drug: Probenecid; 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).
Experimental: Treatment sequence BA 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; Two 500-mg tablets administered as a single oral dose under fasted conditions on Day 1 or Day 22.; Drug: Probenecid; 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).

Outcome Measures

Primary Outcome Measures

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

   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) [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 (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) [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]

   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.

Secondary Outcome Measures

1. 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]

   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) [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 (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) [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]

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

   An adverse event is any untoward medical event that occurs in a subject administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charité Research Organisation GmbH	Berlin		Germany	10117

Sponsors and Collaborators

• Janssen-Cilag International NV

Investigators

• Study Director: Janssen-Cilag International NV Clinical Trial, Janssen-Cilag International NV

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag International NV
• ClinicalTrials.gov Identifier: NCT03105986
• Other Study ID Numbers: CR108300; 64041575RSV1002; 2016-003923-49
• First Posted: Apr 10, 2017
• Last Update Posted: Aug 13, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Probenecid

Study Results

No Results Posted as of Aug 13, 2018