A Study of JNJ-64251330 in Healthy Participants

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 1, Open-Label, Multi-Dose Study to Assess the Systemic and Local Tissue Pharmacokinetics and Pharmacodynamics of JNJ-64251330 in Healthy Participants

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-64251330
* Drug: Tofacitinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Treatment A (JNJ-64251330)<br>Participants will receive JNJ-64251330 (dose 1), once daily for 5 days under fasting conditions. | Drug: JNJ-64251330<br>* JNJ-64251330 tablet will be administered orally.<br>|
| Experimental: Part 1: Treatment B (JNJ-64251330)<br>Participants will receive JNJ-64251330 (dose 1), twice daily for 5 days under fasting conditions. | Drug: JNJ-64251330<br>* JNJ-64251330 tablet will be administered orally.<br>|
| Experimental: Part 1: Treatment C (JNJ-64251330)<br>Participants will receive JNJ-64251330 (dose 2), twice daily for 5 days under fasting conditions. | Drug: JNJ-64251330<br>* JNJ-64251330 tablet will be administered orally.<br>|
| Active Comparator: Part 1: Treatment D (JNJ-64251330)<br>Participants will receive tofacitinib tablet twice daily for 5 days under fasting conditions. | Drug: Tofacitinib<br>* Tofacitinib tablets will be administered orally.<br>|
| Experimental: Part 2: Treatment EF (JNJ-64251330)<br>Participants will receive a single dose of JNJ-64251330 (dose 2), on Day 1 once under fasting conditions (Treatment E) in Period 1 followed by a single dose of JNJ-64251330 (dose 2), on Day 1 once with high fat breakfast (Treatment F) in Period 2. There will be a minimum of 5 days washout between dosing in the two treatment periods. | Drug: JNJ-64251330<br>* JNJ-64251330 tablet will be administered orally.<br>|
| Experimental: Part 2: Treatment FE (JNJ-64251330)<br>Participants will receive a single dose of JNJ-64251330 (dose 2), on Day 1 once with high fat breakfast (Treatment F) in Period 1 followed by a single dose of JNJ-64251330 (dose 2), on Day 1 once under fasting conditions (Treatment E) in Period 2. There will be a minimum of 5 days washout between dosing in the two treatment periods. | Drug: JNJ-64251330<br>* JNJ-64251330 tablet will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Maximum Observed Plasma Concentrations (Cmax) of JNJ-64251330 | Cmax is maximum observed plasma concentrations during a dosing interval. | 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 | 
| Part 1: Trough Observed Plasma Concentration (Ctrough) of JNJ-64251330 | Ctrough is observed plasma concentration immediately prior to dosing on Day 5 and 24 h after last dose. | Predose, 24 hour (h) Postdose on Day 5 | 
| Part 1: Area Under the Plasma Concentration-Time Curve from 0 to 24 Hour (AUC [0-24 h]) of JNJ-64251330 | AUC (0-24 h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose will be evaluated. | 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 | 
| Part 1: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-Last]) of JNJ-64251330 | AUC (0-Last) is defined as area under the plasma concentration versus time curve from time 0 to time of the last quantifiable concentration will be evaluated. | 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 | 
| Part 1: Biopsy Gut (Rectum and Sigmoid Colon) Tissue Concentration of JNJ-64251330 | Biopsy gut (rectum and sigmoid colon) tissue concentration of JNJ-64251330 will be measured using liquid chromatography-mass spectrometry/mass spectrometry (LC MS/MS) assay method to evaluate systemic and local gut (rectum and sigmoid colon) exposure to JNJ-64251330. | Day 6 | 
| Part 1: Change from Baseline in Levels of Phosphorylated Signal Transducer and Activator of Transcription (pSTATs) and other Pan-Janus kinase (JAK) Biomarkers | Change from baseline in levels of pSTATs and other JAK biomarkers in gut (rectum and sigmoid colon) biopsies as a function of compound and dose will be measured to evaluate local tissue pharmacodynamics (PD). | Baseline up to Day 6 | 
| Part 2: Maximum Observed Plasma Concentrations (Cmax) of JNJ-64251330 | Cmax is maximum observed plasma concentrations during a dosing interval. | 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 | 
| Part 2: Time to achieve Maximum Observed Plasma Concentration (Tmax) of JNJ-64251330 | Tmax is the maximum observed plasma concentration. | 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 | 
| Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to 24 Hour (AUC [0-24 h]) of JNJ-64251330 | AUC (0-24 h) defined as area under the plasma concentration-time curve from time 0 to 24 hour postdose will be evaluated. | 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 | 
| Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Time of Last Quantifiable Concentration (AUC [0-Last]) of JNJ-64251330 | AUC (0-Last) defined as area under the plasma concentration versus time curve from time 0 to time of the last quantifiable concentration will be evaluated. | 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 | 
| Part 2: Area Under the Plasma Concentration-Time Curve from Time 0 to Infinite Time (AUC [0-Infinite]) of JNJ-64251330 | AUC (0-Infinite) defined as area under the analyte concentration versus time curve from time 0 to infinite time will be evaluated. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 2: Incidence of Adverse Events (AEs) | Incidence of AEs will be evaluated to assess the safety and tolerability of JNJ 64251330 and tofacitinib. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. | Up to 35 days (Part 1); Up to 39 days (Part 2) | 
| Parts 1 and 2: Number of Participants with Severity of AEs | Severity assessment for an AE will be completed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE Version 5.0). Severity grades ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening or Disabling and Grade 5= Death. | Up to 35 days (Part 1); Up to 39 days (Part 2) | 
| Part 1: Ratio of Gut (Rectum and Sigmoid colon) to Systemic Exposure | Ratio of gut (rectum and sigmoid colon) to systemic exposure will be evaluated to assess the relative exposure of JNJ-64251330 versus tofacitinib. | Up to Day 6 |