A Study of JNJ-64251330 in Healthy Participants

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04552197
• Other study ID #: CR108808
• Secondary ID: 2020-000167-2464
• Status: Completed
• Phase: Phase 1
• Start date: September 2, 2020
• Est. completion date: December 29, 2020

Study information

• Verified date: December 2022
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 29, 2020
• Est. primary completion date: December 29, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• JNJ-64251330
JNJ-64251330 tablet will be administered orally.
• Tofacitinib
Tofacitinib tablets will be administered orally.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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