| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03088644 | A Study to Investigate P2X7 Receptor Occupancy by JNJ-54175446 With the Newly Developed P2X7 Receptor Positron Emission Tomography (PET) Tracer 18F-JNJ-64413739 | PHASE1 | COMPLETED | 16 | — | — | Mar 24, 2017 | Nov 14, 2017 | Apr 27, 2025 | 1 | Belgium |
| NCT03058419 | A Study to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple Probe Substrate Cocktail in Healthy Subjects | PHASE1 | COMPLETED | 16 | — | — | Mar 14, 2017 | May 15, 2017 | Jun 8, 2017 | 1 | Belgium |
| NCT02930694 | A Study to Evaluate the Bioavailability, Safety and Tolerability of a Solid Dosage Formulation Relative to a Suspension of JNJ-54175446 in Healthy Male and Female Participants | PHASE1 | COMPLETED | 32 | — | — | Oct 1, 2016 | Dec 1, 2016 | Feb 16, 2017 | 1 | United States |
| NCT02933762 | A Study in Healthy Participants to Evaluate the Effect of JNJ-54175446 on Amyloid Biomarkers and Cytokine Profiles in Cerebrospinal Fluid and Plasma | PHASE1 | COMPLETED | 25 | — | — | Sep 1, 2016 | Nov 1, 2016 | Feb 3, 2025 | 1 | Belgium |
| NCT02515955 | A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-54175446 in Healthy Male Participants | PHASE1 | COMPLETED | 76 | — | — | Aug 1, 2015 | Mar 1, 2016 | Feb 3, 2025 | 1 | Netherlands |
| NCT02475148 | A Study to Investigate Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of JNJ-54175446 in Healthy Participants | PHASE1 | COMPLETED | 76 | — | — | Jun 1, 2015 | Oct 1, 2015 | Feb 3, 2025 | 1 | Belgium |
The tissue radioactivity will be measured per organ for up to 5 hours after injection of up to 185 megaBecquerel (MBq) of 18F-JNJ-64413739 and corrected for attenuation by computed tomography (CT) transmission scans using PET/CT. These measurements will be used to estimate effective radiation dose per organ and total body.
The Distribution of 18F-JNJ-64413739 in brain will be measured by dynamic PET/magnetic resonance (MR) scans obtained from the time of injection for up to 120 minutes along with measurement of the tracer input function with arterial samples for intact tracer and metabolites to establish the total and regional compartmental kinetics and volume of distribution (V\[t\]) of 18F-JNJ-64413739.
Test Retest Variability within subjects will be assessed based on percent difference in V\[t\] following 18F-JNJ-64413739 PET/MR scans obtained at least 1 Week apart. V\[t\] will be the parameter for the estimated volume of distribution of the tracer derived from the kinetic model that best fits the data from Part B. It will be calculated by formula \[100\*abs (V\[t\]test - V\[t\]retest)/\[( V\[t\]test+ V\[t\]retest)/2\].
Descriptive statistics will be calculated for the plasma concentrations of JNJ-54175446.
Percent reduction in V\[t\] of 18F-JNJ-64413739 in brain regions of interest will be calculated by PET/MR scans obtained at pre and post treatment with single doses of JNJ-54175446.
The Cmax is the maximum observed plasma concentration.
Ctrough is defined as observed plasma concentration of drug just prior to the beginning or at the end of a dosing interval.
The Tmax is defined as actual sampling time to reach maximum observed concentration.
The AUClast is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit) concentration.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Lambda (z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Apparent total clearance is calculated as dose/AUC(0-infinity).
Apparent volume of distribution, calculated as dose/(lambda\[z\]\*AUC\[0-infinity\]).
Parent to metabolite ratio Cmax is defined as the ratio of individual Cmax values between parent and metabolite.
Parent to metabolite ratio (AUC \[Last\]) is defined as ratio of individual (AUC \[Last\]) values between parent and metabolite.
Parent to Metabolite Ratio (AUC \[infinity\]) is defined as the ratio of individual (AUC \[infinity\]) values between parent and metabolite.
The Cmax is the maximum observed plasma concentration.
The Tmax is defined as actual sampling time to reach maximum plasma concentration.
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z); wherein AUC(0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Relative bioavailability, calculated as individual Cmax and AUC treatment ratios (for the comparison of capsule to suspension formulation).
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.
The Cmin is the minimum observed plasma concentration.
The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.
The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC\[tau\]) divided by the dosing interval (tau).
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
The AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't'.
The Cmax is the maximum observed concentration.
Total clearance of drug after extravascular administration, uncorrected for absolute bioavailability
Creatinine clearance was calculated by Cockroft-Gault formula. Creatinine clearance is equal to 140 minus age multiplied by weight and constant (1 for men and 0.85 for women) divided by creatinine in (micro mole per liter).
| Arm | Type | Description |
|---|---|---|
| Part A: 18F-JNJ-64413739 | EXPERIMENTAL | Subjects will receive an intravenous (IV) bolus injection of 18F-JNJ-64413739 at a dose between 150 and 185 megaBecquerel (MBq) on Day 1 of Part A to investigate the total body biodistribution and measure the radiation dosimetry. |
| Part B: 18F-JNJ-64413739 | EXPERIMENTAL | Subjects will receive an IV bolus injection of 18F-JNJ-64413739 at a dose between 150 and 185 MBq on Day 1 of Part B to measure the uptake, distribution, and clearance in brain. |
| Part C: 18F-JNJ-64413739 | EXPERIMENTAL | Subjects will receive an IV bolus injection of 18F-JNJ-64413739 for a PET/MR scan on Day 1 and a repeat 18F-JNJ-64413739 PET/magnetic resonance (MR) scan at least 1 week later to determine the test-retest variability in V\[t\]. 18F-JNJ-64413739 doses will be between 150 and 185 MBq. |
| Part D: JNJ-54175446 + 18F-JNJ-64413739 | EXPERIMENTAL | Subjects will have a baseline 18F-JNJ-64413739 PET/MR scan on Day 1. On Day 2 they will receive JNJ-54175446 (maximum 600 milligram \[mg\]) orally (after light breakfast) and then an IV injection of 18F-JNJ-64413739 four hours after dosing for a PET/MR scan. At least 1 week later, they will receive another dose of JNJ-54175446, and then an IV injection of 18F-JNJ-64413739 four hours later for a second post-treatment PET/MR scan. 18F-JNJ-64413739 doses will be between 150 and 185 MBq. |
| Drug Cocktail + JNJ-54175446 | EXPERIMENTAL | All subjects will receive a single dose of drug cocktail (consisting of midazolam \[2 milligram (mg)\], warfarin \[10 mg\], caffeine \[50 mg\], dextromethorphan \[30 mg\], bupropion \[150 mg\] and omeprazole \[20 mg\]) on Day 1, 7 and 11; JNJ-54175446 150 mg on Day 7, 9, 10 and 11 and JNJ-54175446 600 mg on Day 8. |
| Group 1: Treatment Sequence AB | EXPERIMENTAL | Participants will receive Treatment A \[JNJ-54175446, 50 milligram (mg) capsule\] on Day 1 of period 1 followed by Treatment B \[JNJ-54175446, 50 mg suspension\] on Day 1 of period 2. Both the treatment periods will be separated by washout period of minimum 10 days. |
| Group 1: Treatment Sequence BA | EXPERIMENTAL | Participants will receive Treatment B on Day 1 of period 1 followed by Treatment A on Day 1 of period 2. Both the treatment periods will be separated by washout period of minimum 10 days. |
| Group 2: Treatment Sequence CD | EXPERIMENTAL | Participants will receive Treatment C \[JNJ-54175446, 100 mg capsule\] on Day 1 of period 1 followed by Treatment D \[JNJ-54175446, 100 mg suspension\] on Day 1 of period 2. Both the treatment periods will be separated by washout period of minimum 10 days. |
| Group 2: Treatment Sequence DC | EXPERIMENTAL | Participants will receive Treatment D on Day 1 of period 1 followed by Treatment C on Day 1 of period 2. Both the treatment periods will be separated by washout period of minimum 10 days. |
| Part 1: Cohort A1 (JNJ-54175446 30 milligram[mg]) | EXPERIMENTAL | Healthy elderly participants will receive single dose of 30mg JNJ-54175446. |
| Part 1: Cohort A1 (JNJ-54175446 100mg) | EXPERIMENTAL | Healthy elderly participants will receive single dose of 100mg JNJ-54175446. |
| Part 1: Cohort A1 (JNJ-54175446 300mg) | EXPERIMENTAL | Healthy elderly participants will receive single dose of 300mg JNJ-54175446. |
| Part 1: Cohort A1 (Placebo) | EXPERIMENTAL | Healthy elderly participants will receive single dose of placebo. |
| Part 1: Cohort A2 (JNJ-54175446 D1 mg) | EXPERIMENTAL | Healthy elderly participants will receive an additional dose D1 mg \[less than or equal to (\<=) 600 mg\] of JNJ-54175446, to be determined. |
| Part 1: Cohort A3 (JNJ-54175446 D2 mg) | EXPERIMENTAL | Healthy young participants will receive a single dose D2 mg (\<= 600 mg) of JNJ-54175446, to be determined. |
| Part 1: Cohort A3 (Placebo) | EXPERIMENTAL | Healthy young participants will receive a single dose of placebo. |
| Part 2: Cohort B1 (JNJ-54175446 D3 mg) | EXPERIMENTAL | Healthy elderly participants will receive multiple dose levels D3 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1. |
| Part 2: Cohort B1 (Placebo) | EXPERIMENTAL | Healthy elderly participants will receive placebo determined based on the results from Cohort A1. |
| Part 2: Cohort B2 (JNJ-54175446 D4 mg) | EXPERIMENTAL | Healthy elderly participants will receive multiple dose levels D4 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1. |
| Part 2: Cohort B2 (Placebo) | EXPERIMENTAL | Healthy elderly participants will receive placebo determined based on the results from Cohort A1 |
| Part 2: Cohort B3 (JNJ-54175446 D5 mg) | EXPERIMENTAL | Healthy elderly participants will receive multiple dose levels D5 mg (\<= 450 mg) of JNJ-54175446 determined based on the results from Cohort A1. |
| Part 2: Cohort B3 (Placebo) | EXPERIMENTAL | Healthy elderly participants will receive placebo determined based on the results from Cohort A1 |
| Cohort 1 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Cohort 2 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Cohort 3 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Cohort 4 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Cohort 5 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Cohort 6 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or minocycline 100 mg capsule twice daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Cohort 7 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Cohort 8 | EXPERIMENTAL | Participants will be receiving either JNJ-54175446 at increasing dose levels using 2 oral formulation as suspension for oral dose once daily from Day 1 to Day 17 or placebo matching with JNJ 54175446 once daily from Day 1 to Day 17. |
| Part 1: Cohort 1 | EXPERIMENTAL | Participants will receive either JNJ-54175446 0.5 milligram (mg) or placebo on Day 1. |
| Part 1: Cohort 2 | EXPERIMENTAL | Participants will receive either JNJ-54175446 2.5 mg or placebo on Day 1. |
| Part 1: Cohort 3 | EXPERIMENTAL | Participants will receive either JNJ-54175446 10 mg or placebo on Day 1. |
| Part 1: Cohort 4 | EXPERIMENTAL | Participants will receive either JNJ-54175446 30 mg or placebo on Day 1. |
| Part 1: Cohort 5 | EXPERIMENTAL | Participants will receive either JNJ-54175446 100 mg or placebo on Day 1. |
| Part 1: Cohort 6 | EXPERIMENTAL | Participants will receive either JNJ-54175446 200 mg or placebo on Day 1. |
| Part 2: Cohort 7 | EXPERIMENTAL | Participants will receive JNJ-54175446 on Day 1. The dose of JNJ-54175446 will be determined in part 1 as suitable dose. |
| Part 3: Cohort 8 | EXPERIMENTAL | Participants will receive JNJ-54175446 on Day 1 along with high fat/high calorie breakfast. The dose of JNJ-54175446 will be determined in part 1 as suitable dose. |
| Name | Type | Description |
|---|---|---|
| JNJ-54175446 | DRUG | JNJ-54175446 up to 600 mg suspension for oral dose administration. |
| 18F-JNJ-64413739 | DRUG | 18F-JNJ-64413739 fluid for injection administered intravenously. |
| JNJ-54175446 150 mg | DRUG | Subjects will receive JNJ-54175446 150 mg capsules orally (1\*100 mg + 1\*50 mg) under fasted conditions on Day 7, 9, 10 and 11. |
| JNJ-54175446 600 mg | DRUG | Subjects will receive JNJ-54175446 600 mg (6\*100 mg capsules) orally on Day 8. |
| Midazolam 2 mg | DRUG | Subjects will receive midazolam 2 mg oral emulsion \[2 (milligram per milliliter (mg/mL)\] as a drug cocktail on Day 1, 7 and 11. |
| Warfarin 10 mg | DRUG | Subjects will receive warfarin 10 mg tablets (2\*5 mg) orally as a drug cocktail on Day 1, 7 and 11. |
| Caffeine 50 mg | DRUG | Subjects will receive caffeine 50 mg tablet (1\*50 mg) orally as a drug cocktail on Day 1, 7 and 11. |
| Dextromethorphan 30 mg | DRUG | Subjects will receive dextromethorphan 30 mg capsule (1\*30 mg) orally as a drug cocktail on Day 1, 7 and 11. |
| Bupropion 150 mg | DRUG | Subjects will receive Bupropion 150 mg tablet (1\*150 mg) orally as a drug cocktail on Day 1, 7 and 11. |
| Omeprazole 20 mg | DRUG | Subjects will receive omeprazole 20 mg capsule (1\*20 mg) orally as a drug cocktail on Day 1, 7 and 11. |
| JNJ-54175446 (capsule) | DRUG | Participants will receive JNJ-54175446 capsule at a dose of 50 mg or 100 mg, orally. |
| JNJ-54175446 (suspension) | DRUG | Participants will receive JNJ-54175446 suspension at a dose of 50 mg or 100 mg, orally. |
| Placebo | DRUG | Participants will receive a single oral dose of JNJ-54175446 suspension orally once on Day 1 of part 1 and Day 1 to Day 7 in part 2. |
| Minocycline | DRUG | Participants will receive minocycline 100 mg as capsule twice daily. |
| JNJ 54175446 Matching Placebo | DRUG | Participants will receive placebo matching with JNJ 54175446 once daily orally. |
| D Amphetamine | DRUG | Participants will receive 20 mg d-amphetamine (AMPH) 2 hours after administration of study drug (JNJ-54175446/placebo or minocycline/placebo) on Day 7 and Day 10. |
| D Amphetamine Matching Placebo | DRUG | Participants will receive d-amphetamine (AMPH) matching placebo, 2 hours after administration of study drug (JNJ-54175446/placebo or minocycline/placebo) on Day 7 and Day 10. |
| JNJ 54175446 | DRUG | - |
| High fat/high Calorie Breakfast | OTHER | - |
Inclusion Criteria: * Body mass index (BMI) between 18 and 30 kilogram per square meter (kg/m\^2) inclusive (BMI = weight/height\^2) * Nonsmoker (not smoked for 3 months prior to screening) * Is willing to allow the investigators to place an arterial catheter in the radial artery, is assessed via p...