A Study of JNJ-64251330 in Healthy Participants

NCT04552197 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR1088082020-000167-2464251330EDI1003
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (3)

• Parts 1 and 2: Incidence of Adverse Events (AEs)

  Up to 35 days (Part 1); Up to 39 days (Part 2)

• Parts 1 and 2: Number of Participants with Severity of AEs

  Up to 35 days (Part 1); Up to 39 days (Part 2)

• Part 1: Ratio of Gut (Rectum and Sigmoid colon) to Systemic Exposure

  Up to Day 6

Study Arms (6)

Part 1: Treatment A (JNJ-64251330)

EXPERIMENTAL

Participants will receive JNJ-64251330 (dose 1), once daily for 5 days under fasting conditions.

Drug: JNJ-64251330

Part 1: Treatment B (JNJ-64251330)

EXPERIMENTAL

Participants will receive JNJ-64251330 (dose 1), twice daily for 5 days under fasting conditions.

Drug: JNJ-64251330

Part 1: Treatment C (JNJ-64251330)

EXPERIMENTAL

Participants will receive JNJ-64251330 (dose 2), twice daily for 5 days under fasting conditions.

Drug: JNJ-64251330

Part 1: Treatment D (JNJ-64251330)

ACTIVE COMPARATOR

Participants will receive tofacitinib tablet twice daily for 5 days under fasting conditions.

Drug: Tofacitinib

Part 2: Treatment EF (JNJ-64251330)

EXPERIMENTAL

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

Part 2: Treatment FE (JNJ-64251330)

EXPERIMENTAL

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

Interventions

JNJ-64251330 DRUG

JNJ-64251330 tablet will be administered orally.

Part 1: Treatment A (JNJ-64251330); Part 1: Treatment B (JNJ-64251330); Part 1: Treatment C (JNJ-64251330); Part 2: Treatment EF (JNJ-64251330); Part 2: Treatment FE (JNJ-64251330)

Tofacitinib DRUG

Tofacitinib tablets will be administered orally.

Part 1: Treatment D (JNJ-64251330)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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 \[hCG\])

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

Related Publications (1)

• Ma X, Borzillo G, Kothe MJC, Sanga M, Chu G, Greger JG, Deiteren A, Attiyeh E. A Phase I, Randomized, Multi-Dose Study to Evaluate the Enteric Selectivity and Safety of JAK Inhibitor, Lorpucitinib, in Healthy Participants. Clin Pharmacol Ther. 2024 May;115(5):1075-1084. doi: 10.1002/cpt.3170. Epub 2024 Jan 29.

  PMID: 38159266 DERIVED

MeSH Terms

Interventions

tofacitinib

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 17, 2020
• Study Start: September 2, 2020
• Primary Completion: December 29, 2020
• Study Completion: December 29, 2020
• Last Updated: December 2, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)