A Study of Single and Multiple Ascending Doses of JNJ-61393215 in Healthy Participants

NCT03649997 | Completed Phase 1

• 3 other identifiers: CR1084922018-001944-8061393215EDI1004
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this 3 part study are; Part 1: to investigate the pharmacokinetic (PK), safety and tolerability of JNJ-61393215 suspension (ascending dose levels) after single oral dose administration under fasted conditions, Part 2: to evaluate the relative bioavailability of a solid JNJ-61393215 capsule formulation compared to a suspension of JNJ-61393215 under fasted conditions, and the effect of food on the PK of the solid JNJ-61393215 capsule formulation, Part 3: to investigate the PK, safety, and tolerability of JNJ-61393215 suspension (ascending dose levels) after 7 days of once daily dosing in under fasted conditions.

Conditions

Healthy

Outcome Measures

Primary Outcomes (26)

• Part 1: Maximum Observed Analyte Concentration (Cmax) of JNJ-61393215 Suspension

  Cmax is defined as the maximum observed analyte concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Time to Reach Maximum Observed Analyte Concentration (Tmax) of JNJ-61393215 Suspension

  Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Area Under the Analyte Concentration-time Curve from Time Zero to the Time of Last Measurable Concentration (AUC[0-last]) of JNJ-61393215 Suspension

  AUC(0-last) is defined as the area under the analyte concentration-time curve from time 0 to the time of the last measurable (non-below quantification level \[non-BQL\]) analyte concentration calculated by linear-linear trapezoidal summation.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Area Under the Analyte Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of JNJ-61393215 Suspension

  AUC (0-infinity) is defined as the area under the analyte concentration vs. time curve from time 0 to infinite time, calculated as AUC(0-last) + Clast/lambda(z), where Clast is the last observed measurable (non-BQL) analyte concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Apparent Terminal Elimination Rate Constant (lambda[z]) of JNJ-61393215 Suspension

  lambda(z) is estimated by linear regression using the terminal logarithmic (log)-linear phase of the log transformed concentration vs time data.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Apparent Elimination Half-Life (t1/2) of JNJ-61393215 Suspension

  T1/2 is defined as the apparent terminal elimination half-life and is calculated as 0.693/lambda(z).

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Apparent Oral Clearance (CL/F) of JNJ-61393215 Suspension

  Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Apparent Volume of Distribution (Vdz/F) of JNJ-61393215 Suspension

  Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired analyte concentration of a drug. Apparent volume of distribution after subcutaneous dose (Vz/F) is influenced by the fraction absorbed.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose

• Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of JNJ 61393215 Suspension

  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.

  Up to 7 Weeks

• Part 2: Maximum Observed Analyte Concentration (Cmax) of JNJ-61393215 Capsule

  Cmax is defined as the maximum observed analyte concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose

• Part 2: Area Under the Analyte Concentration-time Curve from Time Zero to the Time of Last Measurable Concentration (AUC[0-last]) of JNJ-61393215 Capsule

  AUC(0-last) is defined as the area under the analyte concentration-time curve from time 0 to the time of the last measurable (non-below quantification level \[non-BQL\]) analyte concentration calculated by linear-linear trapezoidal summation.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose

• Part 2: Area Under the Analyte Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of JNJ-61393215 Capsule

  AUC(0-infinity) is defined as the area under the analyte concentration vs. time curve from time 0 to infinite time, calculated as AUC(0-last) + Clast/lambda(z), where Clast is the last observed measurable (non-BQL) analyte concentration.

  Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose

• Part 3: Maximum Observed Analyte Concentration (Cmax) of JNJ-61393215 Suspension

  Cmax is defined as the maximum observed analyte concentration.

  Predose, 20, 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6 and 12 hours postdose on Day 1 and Day 7; 24 and 48 hours postdose on Day 7

• Part 3: Time to Reach Maximum Observed Analyte Concentration (Tmax) of JNJ-61393215 Suspension

  Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours postdose on Day 1 and Day 7, 24 and 48 hours postdose on Day 7

• Part 3: Area Under the Analyte Concentration-time Curve from Time 0 to 24 Hours (AUC [0-24]) of JNJ-61393215 Suspension

  Area under the analyte concentration vs time curve from time 0 to 24 hours, calculated by linear-linear trapezoidal summation.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours postdose on Day 1 and Day 7, 24 hours postdose on Day 7

• Part 3: Maximum Trough Concentration (Ctrough) of JNJ-61393215 Suspension

  Ctrough is defined as the observed analyte concentration just prior to the beginning or at the end of a dosing interval. Ctrough estimation does not include the concentration that occurs just prior to the first dose.

  Predose on day 1, 2, 3, 4, 5, 6, 7 and 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24 and 48 hours postdose on Day 7

• Part 3: Minimum Observed Analyte Concentration (Cmin) of JNJ-61393215 Suspension

  Cmin is defined as the minimum observed analyte concentration during the dosing interval.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24 and 48 hours postdose on Day 7

• Part 3: Average Analyte Concentration (Cavg) of JNJ-61393215 Suspension

  Cavg is defined as the value of the average analyte concentration at steady state over the dosing interval.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24 and 48 hours postdose on Day 7

• Part 3: Fluctuation Index (FI) of JNJ-61393215 Suspension

  FI is estimated as the percentage fluctuation (variation) between the maximum and minimum analyte concentration at steady state.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7

• Part 3: Volume of Distribution at Steady-State (Vss) of JNJ-61393215 Suspension

  Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC\[0-infinity\])\*(AUMC\[0-infinity\])/AUC\[0-infinity\]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7

• Part 3: Apparent Oral Clearance (CL/F) of JNJ-61393215 Suspension

  Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7

• Part 3: Apparent Terminal Elimination Rate Constant (lambda[z]) of JNJ-61393215 Suspension

  lambda(z) is estimated by linear regression using the terminal logarithmic (log)-linear phase of the log transformed concentration vs time data.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7

• Part 3: Apparent Elimination Half-Life (t1/2) of JNJ-61393215 Suspension

  T1/2 is defined as the apparent terminal elimination half-life and is calculated as 0.693/lambda(z).

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7

• Part 3: Peak by Trough Ratio of JNJ-61393215 Suspension

  Peak by trough ratio is defined as the ratio of the maximum observed analyte concentration to the minimum observed analyte concentration.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7

• Part 3: Observed Accumulation Index Based on AUC (AR AUC) of JNJ-61393215 Suspension

  AR AUC is determined after multiple-dose administration and calculated as AUC (0-24h) on day 7 divided by AUC (0-24h) on day 1.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on Day 1 and 7

• Part 3: Observed Accumulation Index Based on Cmax (ARCmax) of JNJ-61393215 Suspension

  ARCmax is determined after multiple-dose administration and calculated as Cmax on day 7 divided by Cmax on day 1.

  Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on Day 1 and 7

Secondary Outcomes (1)

• Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of JNJ 61393215

  Up to 8 Weeks

Study Arms (12)

Part 1 (Single Ascending Dose [SAD]): Cohort 1

EXPERIMENTAL

Participants will receive single oral dose of JNJ-61393215 145 milligram (mg) suspension or matching placebo on day 1, under fasted conditions.

Drug: JNJ-61393215; Drug: Placebo

Part 1 SAD: Cohort 2

EXPERIMENTAL

Participants will receive single oral dose of JNJ-61393215 225 mg suspension or matching placebo on day 1 under fasted conditions. Dose in this cohort will be determined based on safety and PK data of cohort 1.

Drug: JNJ-61393215; Drug: Placebo

Part 2 Cohort 3: Treatment Sequence CDEF

EXPERIMENTAL

Participants will receive single oral dose of JNJ-61393215 30 mg suspension under fasted condition (Treatment C) in Period 1, then participants will receive single oral dose of JNJ-61393215 30 mg capsule under fasted condition (Treatment D) in Period 2, single oral dose of JNJ-61393215 30 mg capsule with high fat/high-calorie breakfast (Treatment E) in Period 3 followed by single oral dose of JNJ-61393215 30 mg capsule with standardized breakfast (Treatment F) in Period 4, on day 1 of each treatment period. There will be a washout period of at least 7 days between study drug intake in subsequent treatment periods.

Drug: JNJ-61393215

Part 2 Cohort 3: Treatment Sequence DFCE

EXPERIMENTAL

Participants will receive Treatment D in Period 1, then Treatment F in Period 2, then Treatment C in Period 3 followed by Treatment E in Period 4 on Day 1.

Drug: JNJ-61393215

Part 2 Cohort 3: Treatment Sequence ECFD

EXPERIMENTAL

Participants will receive Treatment E in Period 1, then Treatment C in Period 2, then Treatment F in Period 3 followed by Treatment D in Period 4 on Day 1.

Drug: JNJ-61393215

Part 2 Cohort 3: Treatment Sequence FEDC

EXPERIMENTAL

Participants will receive Treatment F in Period 1, then Treatment E in Period 2, then Treatment D in Period 3 followed by Treatment C in Period 4 on Day 1.

Drug: JNJ-61393215

Part 2 Cohort 4: Treatment Sequence GHIJ

EXPERIMENTAL

Participants will receive single oral dose of JNJ-61393215 suspension under fasted condition (Treatment G) in Period 1, then participants will receive single oral dose of JNJ-61393215 capsule under fasted condition (Treatment H) in Period 2, single oral dose of JNJ-61393215 capsule with high fat/high-calorie breakfast (Treatment I) in Period 3 followed by single oral dose of JNJ-61393215 capsule with standardized breakfast (Treatment J) in Period 4, on day 1 of each treatment period. There will be a washout period of at least 7 days between study drug intake in subsequent treatment periods. Dose in this cohort will be based on the results obtained in Part 1.

Drug: JNJ-61393215

Part 2 Cohort 4: Treatment Sequence HJGI

EXPERIMENTAL

Participants will receive Treatment H in Period 1, then Treatment J in Period 2, then Treatment D in Period G followed by Treatment I in Period 4 on Day 1.

Drug: JNJ-61393215

Part 2 Cohort 4: Treatment Sequence IGJH

EXPERIMENTAL

Participants will receive Treatment I in Period 1, then Treatment G in Period 2, then Treatment J in Period 3 followed by Treatment H in Period 4 on Day 1.

Drug: JNJ-61393215

Part 2 Cohort 4: Treatment Sequence JIHG

EXPERIMENTAL

Participants will receive Treatment J in Period 1, then Treatment I in Period 2, then Treatment H in Period 3 followed by Treatment G in Period 4 on Day 1.

Drug: JNJ-61393215

Part 3 Cohort 5: Multiple Ascending Dose

EXPERIMENTAL

Participants will receive oral JNJ-61393215 145 mg suspension or matching placebo once daily for 7 days under fasted conditions.

Drug: JNJ-61393215; Drug: Placebo

Part 3 Cohort 6: Multiple Ascending Dose

EXPERIMENTAL

Participants will receive oral JNJ-61393215 225 mg suspension or matching placebo once daily for 7 days under fasted conditions. Dose may be lowered or increased based on the evaluation of safety and PK of Cohort 5. This dose may be the same as the dose chosen for Cohort 2 (Part 1), or it could be different.

Drug: JNJ-61393215; Drug: Placebo

Interventions

JNJ-61393215 DRUG

Participants will be administered JNJ-61393215 in Part 1, 2 and 3 of study as oral suspension.

Part 1 (Single Ascending Dose [SAD]): Cohort 1; Part 1 SAD: Cohort 2; Part 2 Cohort 3: Treatment Sequence CDEF; Part 2 Cohort 3: Treatment Sequence DFCE; Part 2 Cohort 3: Treatment Sequence ECFD; Part 2 Cohort 3: Treatment Sequence FEDC; Part 2 Cohort 4: Treatment Sequence GHIJ; Part 2 Cohort 4: Treatment Sequence HJGI; Part 2 Cohort 4: Treatment Sequence IGJH; Part 2 Cohort 4: Treatment Sequence JIHG; Part 3 Cohort 5: Multiple Ascending Dose; Part 3 Cohort 6: Multiple Ascending Dose

Placebo DRUG

Participants will be administered JNJ-61393215-matching placebo in Part 1, 2 and 3 of study as oral suspension.

Part 1 (Single Ascending Dose [SAD]): Cohort 1; Part 1 SAD: Cohort 2; Part 3 Cohort 5: Multiple Ascending Dose; Part 3 Cohort 6: Multiple Ascending Dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female of non-childbearing potential
• Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) (including QT interval corrected for heart rate according to Fridericia's formula \[QTcF\] less-than or equal to \[\<=\] 450 milliseconds (ms) for males and \<= 470 ms for females) performed at screening
• Before enrollment, female participants must be of non-childbearing potential, defined as: a) Postmenopausal - A postmenopausal state is defined as no menses for 12 months without an alternative medical cause, as documented by medical records or physician's notes; b) Permanently sterile - Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy
• Body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m\^2) (inclusive), and body weight \< than 50 kg at screening
• Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic at screening

You may not qualify if:

• Clinically significant abnormal values for hematology, biochemistry, or urinalysis at screening as deemed appropriate by the investigator
• Participants has any liver function test (including alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma-glutamyltransferase \[GGT\], alkaline phosphatase \[ALP\], and bilirubin) at screening more than (\>)1.5\* upper limit of normal (ULN)
• Participants has estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation \< 61 milliliter (mL) / minute /1.73 per square meter (m\^2) at screening
• Clinically significant abnormal physical examination, vital signs, or 12 lead ECG at screening as deemed appropriate by the investigator
• Known allergies, hypersensitivity, or intolerance to JNJ-61393215 or its excipients (or lactose)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

PRA Health Sciences

Groningen, NZ 9728, Netherlands

Location

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: August 28, 2018
• Study Start: August 28, 2018
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

NL (1)