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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
36
JNJ-64251330 tablet will be administered orally.
Tofacitinib tablets will be administered orally.
Clinical Pharmacology Unit
Merksem, Belgium
Part 1: Maximum Observed Plasma Concentrations (Cmax) of JNJ-64251330
Cmax is maximum observed plasma concentrations during a dosing interval.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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.
Time frame: 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.
Time frame: 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.
Time frame: Up to Day 6