A Study to Investigate the Safety, Tolerability and Pharmacokinetics of JNJ-64991524 in Healthy Participants

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of JNJ-64991524 in Healthy Participants

The purpose of this study is to evaluate safety and tolerability of JNJ-64991524 compared with placebo after administration of single ascending oral doses of JNJ-64991524 (Part 1) and multiple ascending oral doses of JNJ-64991524 (Part 2) in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-64991524 Dose Level 1; Drug: Placebo; Drug: JNJ-64991524 Dose Level 2; Drug: JNJ-64991524 Dose Level 3; Drug: JNJ-64991524 Dose Level 4; Drug: JNJ-64991524 Dose Level 5; Drug: JNJ-64991524 Dose Level 6; Drug: JNJ-64991524 Dose Level 7; Drug: JNJ-64991524 Dose Level 8; Drug: JNJ-64991524 Dose Level 9

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Weigh at least 50 kilogram (kg), and have a body mass index (BMI) of 18 kg/ meter (m)^2 to 30 kg/m^2, inclusive, at screening
• Be otherwise healthy on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening and Day-1. This determination must be recorded in the participant's source documents and initialed by the investigator
• Be otherwise healthy on the basis of clinical laboratory tests performed at screening and Day -1. If the results of the serum chemistry panel, including liver enzymes, white blood cell count and hematocrit, 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 or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and confirmed initialed by the investigator
• Have the platelet count pretreatment clinical laboratory values not below the normal range during Screening and Day -1
• A woman must have a negative serum pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test on Day -2

Exclusion Criteria:

• History of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• Known allergies, hypersensitivity, or intolerance to JNJ-64991524 or its excipients
• History of severe allergic reaction, angioedema, or anaphylaxis to drugs or food
• Has a history of malignancy before screening. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or a malignancy which is considered cured with minimal risk of recurrence
• Has a history of or is infected with human immunodeficiency virus (HIV [positive serology for HIV antibody]); tests positive for hepatitis B virus (HBV) infection; has antibodies to hepatitis C virus (HCV) at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1:JNJ-64991524 Dose Level (DL) 1 or Placebo(SAD Part 1); Participants will receive a single oral dose (Dose level 1) of either JNJ-64991524 or placebo capsules after an overnight fast (at least 10 hours) on Day 1 of Part 1.	Drug: JNJ-64991524 Dose Level 1; Participants will receive JNJ-64991524 at a Dose Level 1 in SAD Part 1 of study.; Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.
Experimental: Cohort 2: JNJ-64991524 DL 2 or Placebo (SAD Part 1); Participants will receive a single oral dose (Dose level 2) of either JNJ-64991524 or placebo capsules after an overnight fast (at least 10 hours) on Day 1 of Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 2; Participants will receive JNJ-64991524 at a Dose Level 2 in SAD Part 1 of study.
Experimental: Cohort 3: JNJ-64991524 DL 3 or Placebo (SAD Part 1); Participants will receive a single oral dose (Dose level 3) of either JNJ-64991524 or placebo capsules after an overnight fast (at least 10 hours) on Day 1 of Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 3; Participants will receive JNJ-64991524 at a Dose Level 3 in SAD Part 1 of study.
Experimental: Cohort 4:JNJ-64991524 DL 4 or Placebo (SAD Part 1:Fasted-Fed); Participants will receive a single oral dose (Dose level 4) of either JNJ-64991524 or placebo capsules in a fasted condition on Day 1 and fed condition, on Day 7.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 4; Participants will receive JNJ-64991524 at a Dose Level 4 in SAD Part 1 of study.
Experimental: Cohort 5: JNJ-64991524 DL 5 or Placebo (SAD Part 1); Participants will receive a single oral dose (Dose level 5) of JNJ-64991524 or placebo after an overnight fast (at least 10 hours) on Day 1 of Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 5; Participants will receive JNJ-64991524 at a dose of Dose Level 5 in SAD Part 1 of study.
Experimental: Cohort 6: JNJ-64991524 DL 6 or Placebo (SAD Part 1); Participants will receive a single oral dose (Dose level 6) of JNJ-64991524 or placebo after an overnight fast (at least 10 hours) on Day 1 of Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 6; Participants will receive JNJ-64991524 at a Dose Level 6 in SAD Part 1 and MAD part 2 of study.
Experimental: Cohort 1: JNJ-64991524 DL 7 or Placebo (MAD Part 2); Participants will receive an oral dose (Dose level 7) JNJ-64991524 or placebo capsules once daily for 14 days in fasted or fed condition in Part 2. Fasted/fed condition will be determined based on tolerability and pharmacokinetics (PK) from Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 7; Participants will receive JNJ-64991524 at a dose of Dose Level 7 in MAD Part 2 of study for 14 days.
Experimental: Cohort 2: JNJ-64991524 DL 8 or Placebo (MAD Part 2); Participants will receive an oral dose (Dose level 8) JNJ-64991524 or placebo capsules once daily for 14 days in fasted or fed condition in Part 2. Fasted/fed condition will be determined based on tolerability and PK from Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 8; Participants will receive JNJ-64991524 at a Dose Level 8 in MAD Part 2 of study for 14 days.
Experimental: Cohort 3: JNJ-64991524 DL 9 or Placebo (MAD Part 2); Participants will receive an oral dose (Dose level 9) JNJ-64991524 or placebo capsules once daily for 14 days in fasted or fed condition in Part 2. Fasted/fed condition will be determined based on tolerability and PK from Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 9; Participants will receive JNJ-64991524 at a Dose Level 9 in MAD Part 2 of study for 14 days.
Experimental: Cohort 4: JNJ-64991524 DL 6 or Placebo (MAD Part 2); Participants will receive an oral dose (Dose level 6) of JNJ-64991524 or placebo capsules once daily for 14 days in fasted or fed condition in Part 2. Fasted/fed condition will be determined by tolerability and PK from Part 1.	Drug: Placebo; Participants will receive matching placebo in all cohorts on Day 1 in Part 1 and Part 2 of the study.; Drug: JNJ-64991524 Dose Level 6; Participants will receive JNJ-64991524 at a Dose Level 6 in SAD Part 1 and MAD part 2 of study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Single Ascending Dose (SAD): Number of Participants with Treatment Emergent Adverse Events (AEs) as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Treatment-emergent were events between administration of study drug and up to Day 20 that were absent before treatment or that worsened relative to pre-treatment state.	Up to Day 20
Part 2: Multiple Ascending Dose (MAD): Number of Participants with Treatment Emergent Adverse Events as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Treatment-emergent were events between administration of study drug and up to Day 28 that were absent before treatment or that worsened relative to pre-treatment state.	Up to Day 28
Number of Participants with Abnormalities in Vital Signs, Physical Examinations, Electrocardiogram (ECG), Cardiac Telemetry and Clinically Significant Laboratory Findings	Number of participants with abnormalities in vital signs, physical examinations, ECG, cardiac telemetry and clinically significant laboratory findings will be measured.	Pre-dose, up to Day 20 (SAD) and up to Day 28 (MAD)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of JNJ-64991524	Plasma concentration assessment will be done to characterize the pharmacokinetics (PK) of JNJ-64991524.	Pre-dose, up to Day 20 (SAD) and up to Day 28 (MAD)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): November 20, 2018
• Study Completion (Actual): November 20, 2018

Study Registration Dates

• First Submitted: November 15, 2017
• First Submitted That Met QC Criteria: November 15, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): January 24, 2019
• Last Update Submitted That Met QC Criteria: January 22, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: CR108376; 2017-000229-11 (EudraCT Number); 64991524EDI1001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No