Clinical trial NCT04552197: A Study of JNJ-64251330 in Healthy Participants
Official title: A Phase 1, Open-Label, Multi-Dose Study to Assess the Systemic and Local Tissue Pharmacokinetics and Pharmacodynamics of JNJ-64251330 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-09-17
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate: systemic and local gut (rectum and sigmoid colon) exposure to JNJ-64251330, local tissue Pharmacodynamics (PD) using gut (rectum and sigmoid colon) biopsies (Part 1) and the effect of food on the rate and extent of absorption of JNJ-64251330 from oral tablet dosed with or without food (Part 2).


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI; weight \[kilogram {kg}\]/height\^2 \[meter {m}\]\^2) between 18.0 and 30.0 kilograms per meter square (kg/m\^2) (inclusive), and body weight not less than 50.0 kg
* 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function, including: QTc interval less than or equal to (\<=) 450 milliseconds (ms) for men and \<= 470 ms for women
* Healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, lipid panel, hematology, coagulation or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
* Have participant-reported normal consistency, regular bowel movements
* A woman must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[hCG\])

Exclusion Criteria:

* History of hepatic or renal insufficiency; significant cardiac, vascular, pulmonary, endocrine, hematologic, rheumatologic, neurologic, oncologic, or psychiatric disease, or metabolic disturbances or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
* Active or chronic infection, a nontuberculous mycobacterial infection, or opportunistic infection (example, pneumocystosis and aspergillosis)
* History of severe allergic reaction to midazolam
* Contraindications to the use of tofacitinib per summary of product characteristics (SmPC)\^14/ local prescribing information
* Female participant who is a breastfeeding mother

Primary outcomes:
measure: Part 1: Maximum Observed Plasma Concentrations (Cmax) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1 and Day 5; Predose on Day 2
measure: Part 1: Trough Observed Plasma Concentration (Ctrough) of JNJ-64251330
timeFrame: Predose, 24 hour (h) Postdose on Day 5
measure: Part 1: Area Under the Plasma Concentration-Time Curve from 0 to 24 Hour (AUC [0-24 h]) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 14 h, 24 h Postdose on Day 1 and Day 5; Predose on Day 2
measure: Part 1: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-Last]) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 14 h, 24 h Postdose on Day 1 and Day 5; Predose on Day 2
measure: Part 1: Biopsy Gut (Rectum and Sigmoid Colon) Tissue Concentration of JNJ-64251330
timeFrame: Day 6
measure: Part 1: Change from Baseline in Levels of Phosphorylated Signal Transducer and Activator of Transcription (pSTATs) and other Pan-Janus kinase (JAK) Biomarkers
timeFrame: Baseline up to Day 6
measure: Part 2: Maximum Observed Plasma Concentrations (Cmax) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
measure: Part 2: Time to achieve Maximum Observed Plasma Concentration (Tmax) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
measure: Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to 24 Hour (AUC [0-24 h]) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h Postdose on Day 2
measure: Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-Last]) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
measure: Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Infinite Time (AUC [0-Infinite]) of JNJ-64251330
timeFrame: Predose, 0.25 hour (h), 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h Postdose on Day 1; 24 h, 32 h, 36 h Postdose on Day 2; 48 h Postdose on Day 3
Secondary outcomes:
measure: Parts 1 and 2: Incidence of Adverse Events (AEs)
timeFrame: Up to 35 days (Part 1); Up to 39 days (Part 2)
measure: Parts 1 and 2: Number of Participants with Severity of AEs
timeFrame: Up to 35 days (Part 1); Up to 39 days (Part 2)
measure: Part 1: Ratio of Gut (Rectum and Sigmoid colon) to Systemic Exposure
timeFrame: Up to Day 6
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: