Healthy
Conditions
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.
Interventions
DRUGJNJ-61393215
Participants will be administered JNJ-61393215 in Part 1, 2 and 3 of study as oral suspension.
DRUGPlacebo
Participants will be administered JNJ-61393215-matching placebo in Part 1, 2 and 3 of study as oral suspension.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 3: Observed Accumulation Index Based on Cmax (ARCmax) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on Day 1 and 7 | ARCmax is determined after multiple-dose administration and calculated as Cmax on day 7 divided by Cmax on day 1. |
| Part 1: Maximum Observed Analyte Concentration (Cmax) of JNJ-61393215 Suspension | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | Cmax is defined as the maximum observed analyte concentration. |
| Part 1: Time to Reach Maximum Observed Analyte Concentration (Tmax) of JNJ-61393215 Suspension | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | Tmax is defined as actual sampling time to reach maximum observed analyte concentration. |
| 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 | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 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. |
| Part 1: Area Under the Analyte Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of JNJ-61393215 Suspension | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 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. |
| Part 1: Apparent Terminal Elimination Rate Constant (lambda[z]) of JNJ-61393215 Suspension | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | lambda(z) is estimated by linear regression using the terminal logarithmic (log)-linear phase of the log transformed concentration vs time data. |
| Part 1: Apparent Elimination Half-Life (t1/2) of JNJ-61393215 Suspension | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | T1/2 is defined as the apparent terminal elimination half-life and is calculated as 0.693/lambda(z). |
| Part 1: Apparent Oral Clearance (CL/F) of JNJ-61393215 Suspension | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 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. |
| Part 1: Apparent Volume of Distribution (Vdz/F) of JNJ-61393215 Suspension | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 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. |
| Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of JNJ 61393215 Suspension | Up to 7 Weeks | 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. |
| Part 2: Maximum Observed Analyte Concentration (Cmax) of JNJ-61393215 Capsule | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose | Cmax is defined as the maximum observed analyte concentration. |
| 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 | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose | 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. |
| Part 2: Area Under the Analyte Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of JNJ-61393215 Capsule | Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose | 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. |
| Part 3: Maximum Observed Analyte Concentration (Cmax) of JNJ-61393215 Suspension | 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 | Cmax is defined as the maximum observed analyte concentration. |
| Part 3: Time to Reach Maximum Observed Analyte Concentration (Tmax) of JNJ-61393215 Suspension | 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 | Tmax is defined as actual sampling time to reach maximum observed analyte concentration. |
| Part 3: Area Under the Analyte Concentration-time Curve from Time 0 to 24 Hours (AUC [0-24]) of JNJ-61393215 Suspension | 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 | Area under the analyte concentration vs time curve from time 0 to 24 hours, calculated by linear-linear trapezoidal summation. |
| Part 3: Maximum Trough Concentration (Ctrough) of JNJ-61393215 Suspension | 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 | 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. |
| Part 3: Minimum Observed Analyte Concentration (Cmin) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24 and 48 hours postdose on Day 7 | Cmin is defined as the minimum observed analyte concentration during the dosing interval. |
| Part 3: Average Analyte Concentration (Cavg) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24 and 48 hours postdose on Day 7 | Cavg is defined as the value of the average analyte concentration at steady state over the dosing interval. |
| Part 3: Fluctuation Index (FI) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7 | FI is estimated as the percentage fluctuation (variation) between the maximum and minimum analyte concentration at steady state. |
| Part 3: Volume of Distribution at Steady-State (Vss) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7 | 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. |
| Part 3: Apparent Oral Clearance (CL/F) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7 | 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. |
| Part 3: Apparent Terminal Elimination Rate Constant (lambda[z]) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7 | lambda(z) is estimated by linear regression using the terminal logarithmic (log)-linear phase of the log transformed concentration vs time data. |
| Part 3: Apparent Elimination Half-Life (t1/2) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7 | T1/2 is defined as the apparent terminal elimination half-life and is calculated as 0.693/lambda(z). |
| Part 3: Peak by Trough Ratio of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 and 48 hours postdose on Day 7 | Peak by trough ratio is defined as the ratio of the maximum observed analyte concentration to the minimum observed analyte concentration. |
| Part 3: Observed Accumulation Index Based on AUC (AR AUC) of JNJ-61393215 Suspension | Predose, 20 and 40 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose on Day 1 and 7 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of JNJ 61393215 | Up to 8 Weeks | 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. |
Countries
Netherlands
Outcome results
None listed