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

Healthy Clinical Trial

Official title:

A Multi-cohort, Randomized Study in Healthy Subjects to Assess the Pharmacokinetics and Safety of Single and Multiple Ascending Doses of JNJ-61393215 (Suspension), and to Assess the Relative Bioavailability, and the Effect of Food on the Pharmacokinetics, of a New Solid Formulation (Capsules) of JNJ-61393215

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03649997
• Other study ID #: CR108492
• Secondary ID: 2018-001944-8061
• Status: Completed
• Phase: Phase 1
• Start date: August 28, 2018
• Est. completion date: December 14, 2018

Study information

• Verified date: January 2019
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: December 14, 2018
• Est. primary completion date: December 14, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Healthy

Intervention

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

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of JNJ 61393215	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 8 Weeks