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JNJ-53718678

Phase 1

Healthy | Small molecule | Other |Johnson & Johnson|Last Updated: Feb 3, 2025

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials6
Total Enrollment213
FDA Designations
No designations recorded
Clinical Trials (6)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT04090086A Study to Assess Interaction Between JNJ-64417184 and JNJ-53718678 After Single and Multiple Dosing in Healthy ParticipantsPHASE1 COMPLETED 16Sep 16, 2019Dec 10, 2019Feb 3, 20251 Netherlands
NCT03696459A Study to Evaluate the Effect of JNJ-53718678 on the Cardiac Repolarization Interval in Healthy Adult ParticipantsPHASE1 COMPLETED 52Oct 2, 2018Dec 13, 2019Feb 18, 20201 Belgium
NCT03002779A Study to Characterize the Absorption, Metabolism, and Excretion of 14C-JNJ-53718678 After a Single Oral Dose in Healthy Male ParticipantsPHASE1 COMPLETED 6Jan 26, 2017Mar 20, 2017May 31, 20171 Netherlands
NCT02945007A Study to Assess the Relative Oral Bioavailability of a Single Dose of JNJ-53718678 Administered as Oral Concept Formulation Compared to the Current Oral Solution and to Assess the Effect of Food on the Pharmacokinetics of Oral Concept FormulationPHASE1 COMPLETED 82Nov 8, 2016Jan 16, 2020Mar 10, 20201 Belgium
NCT02729467A Study to Assess the Effects of Itraconazole and Rifampicin on the Single-Dose Pharmacokinetics of JNJ-53718678 in Healthy AdultsPHASE1 COMPLETED 33Mar 1, 2016Jun 1, 2016Feb 3, 20251 United States
NCT02398591A Study to Investigate Safety, Tolerability, and Pharmacokinetics of JNJ 53718678 in Healthy Japanese Adult ParticipantsPHASE1 COMPLETED 24Apr 1, 2015Jul 15, 2015Jul 11, 20171 United Kingdom
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Study Endpoints
Primary Endpoints
Observed Plasma Analyte Concentration (Ctrough) of JNJ-53718678
Day 2, 3, 4, 5 and 6: predose; Day 7: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 18 hours postdose

Ctrough is defined as observed plasma analyte concentration just prior to the beginning of a dosing interval.

Ctrough of JNJ-64417184
Day 2, 3, 4, 5 and 6: predose; Day 7: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 18 hours postdose

Ctrough is defined as observed plasma analyte concentration just prior to the beginning of a dosing interval.

Maximum Observed Plasma Analyte Concentration (Cmax) of JNJ-53718678
Day 1 and 7: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 18 hours postdose

Cmax is defined as maximum observed plasma analyte concentration.

Cmax of JNJ-64417184
Day 1 and 7: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 18 hours postdose

Cmax is defined as maximum observed plasma analyte concentration.

Area Under the Plasma Concentration-time Curve from Time of Administration up to 24 Hours Postdose (AUC[24h]) of JNJ-53718678
Up to 24 hours postdose

AUC24h is defined as AUC from time 0 to 24 hours postdose.

AUC24h of JNJ-64417184
Up to 24 hours postdose

AUC24h is defined as AUC from time 0 to 24 hours postdose.

Part 2: Placebo-Corrected Change from Baseline in QT Interval Corrected for Heart Rate (QTc) for JNJ-53718678
Baseline and Day 1

Placebo-corrected change from baseline in QT interval corrected for heart rate (QTc) will be determined. The mean change from baseline in QTc in placebo treatment will be subtracted from the mean change from baseline in JNJ-53718678 treatment at the same time point to generate placebo-corrected change from baseline in QTc, which will be presented.

Mass Balance of JNJ-53718678 in Healthy Adult Male Participants.
Up to Day 10

Total mass balance calculated by D(dose) urine, total (percent \[%\]) + D feces, total (%) + D duodenal, total (%) where D urine, total is the total percentage of the dose excreted into urine, calculated as 100 \* (Ae total \[total amount excreted into urine, calculated by adding the amounts of the individual intervals together\] /Dose); D feces,total is the total percentage of the dose excreted into feces, calculated as 100 \* (Ae total \[total amount excreted into feces, calculated by adding the amounts of the individual stools together\]/Dose) and D duodenal, total is defined as total percentage of the dose collected in all duodenal samples collectively, calculated as % of dose.

Metabolic profiles of JNJ-53718678 in plasma, duodenal fluid, urine, and feces samples with radio high-performance liquid chromatography analysis
Up to Day 6

Metabolite profiling will be performed with radio high-performance liquid chromatography.

Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678
Up to 72 hour of Post-dose

The Cmax is the maximum observed plasma concentration.

Area Under the Plasma ConcentrationTime Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC [0last]) of JNJ-53718678
Up to 72 hour of Post-dose

The AUC (0-last) is the area under the plasma concentration time curve from time 0 to the time of the last measurable non-below quantification limit concentration, calculated by liner-linear trapezoidal summation.

Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of JNJ-53718678
Up to 72 hour of Post-dose

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.

Relative Bioavailability of JNJ-53718678
Up to 72 hour of Post-dose

The relative bioavailability based on Cmax, AUC(0last), and AUC(0-inf) will be estimated as 100\*Test/Reference, where Test is defined as the pharmacokinetic parameters of oral JNJ-53718678 and Reference is defined as currently existing oral solution G024.

Effect of Food on the Bioavailabilty of JNJ-53718678
Up to 72 hour of Post-dose

The effect of food will be evaluated by comparing the pharmacokinetics of JNJ-53718678 under fed conditions with the currently existing oral solution under fasted conditions.

Maximum Observed Analyte Concentration (Cmax)
Up to 11 days

The Cmax is the maximum observed analyte concentration after the JNJ-53718678 doses on Day 1, Day 4 (Panel 2 only) and Day 9.

Area Under the Analyte Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC [0-last])
Up to 11 days

The (AUC \[0-last\]) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration after the JNJ-53718678 doses on Day 1 and Day 9.

Area Under the Analyte Concentration-Time Curve From Time 0 to Infinite Time (AUC [0-infinity])
Up to 11 days

The AUC (0-infinity) is the area under the Analyte concentration-time curve from time 0 to infinite time after the JNJ-53718678 doses on Day 1 and Day 9, calculated as the sum of AUC(0-last) and C(0-last)/lambda(z), wherein AUC(0-last) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentrations; C(0-last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

Area Under the Analyte Concentration-time curve From Time 0 to 24h (AUC24h)
Up to 11 days

The AUC24h is the area under the analyte concentration-time curve from time 0 to 24h after dosing on Day 1 and Day 4 (Panel 2 only).

Ratio of Individual Cmax Values Between Test and Reference Treatment (Ratio Cmax, test/reference)
Up to 11 days

Ratio Cmax, test/reference is the ratio of individual Cmax values between test (JNJ-53718678 with itraconazole, on Day 9, or JNJ-53718678 with rifampicin, on Day 4 and Day 9) and reference (without itraconazole or rifampicin, on Day 1) treatments.

Ratio of Individual AUC24h Values Between Test and Reference Treatment (Ratio AUC24h, test/reference)
Up to 11 days

Ratio AUC24h, test/reference is the ratio of individual AUC24h values between test (JNJ-53718678 with rifampicin, on Day 4) and reference (without rifampicin, on Day 1) treatments.

Ratio of Individual AUClast Values Between Test and Reference Treatment (Ratio AUClast, test/reference)
Up to 11 days

Ratio AUClast, test/reference is the ratio of individual AUClast values between test (JNJ-53718678 with itraconazole or rifampicin, on Day 9) and reference (without itraconazole or rifampicin, on Day 1) treatments.

Ratio of Individual AUC(infinity) Values Between Test and Reference Treatment (Ratio AUC[infinity], test/reference)
Up to 11 days

Ratio AUC(infinity), test/reference is the ratio of individual AUC(infinity) values between test (JNJ-53718678 with itraconazole or rifampicin, on Day 9) and reference (without itraconazole or rifampicin, on Day 1) treatments.

Maximum Observed Plasma Concentration (Cmax)
Up to 72 hours post dose

The Cmax is the maximum observed plasma concentration.

Time to Reach Maximum Observed Plasma Concentration (Tmax)
Up to 72 hours post dose

The Tmax is defined as actual sampling time to reach maximum observed JNJ 53718678 concentration.

Time to Last Quantifiable Plasma Concentration (Tlast)
Up to 72 hours post dose

The Tlast is the time to last observed quantifiable plasma concentration.

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
Up to 72 hours post dose

The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])
Up to 72 hours post dose

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.

Apparent Initial Elimination Rate Constant (lambda [alpha])
Up to 72 hours post dose

Apparent initial elimination rate constant, determined by linear regression of the data points within the first elimination phase of the ln-linear plasma concentration-time curve.

Elimination Rate Constant (Lambda[z])
Up to 72 hours post dose

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.

Apparent Initial Elimination Half-life (t1/2[alpha])
Up to 72 hours post dose

Apparent initial elimination half-life is calculated as 0.693/lambda(alpha).

Elimination Half-Life (t1/2)
Up to 72 hours post dose

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).

Total Apparent Clearance (CL/F)
Up to 72 hours post dose

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.

Apparent Volume of Distribution (Vd/F)
Up to 72 hours post dose

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 plasma concentration of a drug. Apparent volume of distribution after subcutaneous dose (Vd/F) is influenced by the fraction absorbed.

Number of Participants With Adverse Events
From sign of informed consent up to end of study (Day 14)

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.

Secondary Endpoints
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Up to 42 days
Part 1: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Approximately up to 9 weeks
Part 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Approximately up to 12 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelCROSSOVER
PurposeOTHER
Treatment Arms
ArmTypeDescription
Treatment Sequence 1: Treatment ABCEXPERIMENTALParticipants will receive Treatment A (JNJ-53718678 once daily for 7 days) in Treatment Period 1, followed by Treatment B (JNJ-64417184 once daily for 7 days) in Treatment Period 2, followed by Treatment C (JNJ-53718678 once daily + JNJ-64417184 once daily for 7 days) in Treatment Period 3. There will be a washout period of at least 7 days between the treatment periods.
Treatment Sequence 2: Treatment BCAEXPERIMENTALParticipants will receive Treatment B in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment A in Treatment Period 3. There will be a washout period of at least 7 days between the treatment periods.
Treatment Sequence 3: Treatment CABEXPERIMENTALParticipants will receive Treatment C in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment B in Treatment Period 3. There will be a washout period of at least 7 days between the treatment periods.
Treatment Sequence 4: Treatment ACBEXPERIMENTALParticipants will receive Treatment A in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment B in Treatment Period 3. There will be a washout period of at least 7 days between the treatment periods.
Treatment Sequence 5: Treatment BACEXPERIMENTALParticipants will receive Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment C in Treatment Period 3. There will be a washout period of at least 7 days between the treatment periods.
Treatment Sequence 6: Treatment CBAEXPERIMENTALParticipants will receive Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment A in Treatment Period 3. There will be a washout period of at least 7 days between the treatment periods.
Part 1 (Dose Escalation): Panel 1EXPERIMENTALParticipants will receive single oral dose of JNJ-53718678, 2000 milligram (mg) suspension or matching placebo on Day 1, under fasted conditions.
Part 1 (Dose Escalation): Panel 2EXPERIMENTALParticipants will receive single oral dose of JNJ-53718678, of maximum 3000 mg suspension or matching placebo on Day 1, under fasted conditions.
Part 1 (Dose escalation): Panel 3EXPERIMENTALParticipants will receive single oral dose of JNJ-53718678 4500 mg suspension (this dose may be used in Part 2, Treatment F) or matching placebo on Day 1, under fasted condition.
Part 1 (Dose Escalation): Panel 4 (Optional)EXPERIMENTALParticipants will receive single oral dose of JNJ-53718678 (dose to be decided \[this dose may be used in Part 2, Treatment F\]) suspension or matching placebo on Day 1, under fasted condition, if 4500 mg dose in Panel 3 is considered safe and tolerable and if pharmacokinetic data require further dose escalation to reach the target exposure.
Part 2 Group 1: Treatment Sequence EHFGEXPERIMENTALParticipants will receive single oral dose of JNJ-53718678, 500 mg suspension with single oral dose of moxifloxacin placebo and JNJ 53718678 placebo (Treatment E) in Period 1, then participants will receive single oral dose of moxifloxacin 400 mg with single oral dose of JNJ-53718678 placebo (Treatment H) in Period 2 then will receive single oral dose of JNJ-53718678, 4500 mg (dose will be based on review of safety, tolerability, and PK data obtained in Part 1 \[either from Panel 3 or 4\], this dose may be lower/higher) suspension with single oral dose of moxifloxacin placebo (Treatment F) in Period 3 followed by single oral dose of JNJ-53718678 placebo with single oral dose of moxifloxacin placebo (Treatment G) 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.
Part 2 Group 2: Treatment Sequence FEGHEXPERIMENTALParticipants will receive Treatment F in Period 1, then Treatment E in Period 2, then Treatment G in Period 3 followed by Treatment H in Period 4 on Day 1 of each treatment period.
Part 2 Group 3: Treatment Sequence GFHEEXPERIMENTALParticipants will receive Treatment G in Period 1, then Treatment F in Period 2, then Treatment H in Period 3 followed by Treatment E in Period 4 on Day 1 of each treatment period.
Part 2 Group 4: Treatment Sequence HGEFEXPERIMENTALParticipants will receive Treatment H in Period 1, then Treatment G in Period 2, then Treatment E in Period 3 followed by Treatment F in Period 4 on Day 1 of each treatment period.
JNJ-53718678EXPERIMENTAL -
JNJ-53718678: PART 1EXPERIMENTALParticipants will receive a single dose of JNJ-53718678 500 mg under fasted conditions on day 1 for treatment A (solution) and B (novel concept formulation 1), and under fed condition for treatment C (novel concept formulation 1).
JNJ-53718678: PART 2EXPERIMENTALParticipants will receive a single dose of JNJ-53718678 500 mg under fasted conditions on day 1 for treatment A (solution) and D (novel concept formulation 2), and under fed condition for treatment E (novel concept formulation 2). Part 2 of the study is optional and might be performed depending on the availability of concept formulations and the result of previous part.
JNJ-53718678: PART 3EXPERIMENTALParticipants will receive a single dose of JNJ-53718678 500 mg under fasted conditions on day 1 for treatment A (solution) and F (novel concept formulation 3), and under fed condition for treatment G (novel concept formulation 3). Part 3 of the study is optional and might be performed depending on the availability of concept formulations and the result of previous part.
JNJ-53718678: PART 4EXPERIMENTALParticipants will receive a single dose of JNJ-53718678 500 mg under fasted conditions on day 1 for treatment A (solution) and H (novel concept formulation 4), and under fed condition for treatment I (novel concept formulation 4). Part 4 of the study is optional and might be performed depending on the availability of concept formulations and the result of previous part.
JNJ-53718678: PART 5EXPERIMENTALParticipants will receive a single dose of JNJ-53718678 500 mg under fasted conditions on day 1 for treatment A (solution) and J (novel concept formulation 5), and under fed condition for treatment K (novel concept formulation 5). Part 5 of the study is optional and might be performed depending on the availability of concept formulations and the result of previous part.
JNJ-53718678: PART 6EXPERIMENTALParticipants will receive a single dose of JNJ-53718678 500 mg under fasted conditions on day 1 for treatment A (solution) and L (novel concept formulation 6), and under fed condition for treatment M (novel concept formulation 6). Part 6 of the study is optional and might be performed depending on the availability of concept formulations and the result of previous part.
JNJ-53718678: PART 7EXPERIMENTALParticipants will receive a single dose of JNJ-53718678 500 mg under fasted conditions on day 1 for treatment A (solution) and N (novel concept formulation 7), and under fed condition for treatment O (novel concept formulation 7). Part 7 of the study is optional and might be performed depending on the availability of concept formulations and the result of previous part.
JNJ-53718678: PART 8EXPERIMENTALParticipants will receive a single dose of JNJ-53718678, 500 mg oral solution under fasted or fed conditions on day 1 for treatment A and P (oral concept formulation 1, 2, 3, 4, 5, 6 or 7) and under fed conditions for treatment Q (oral concept formulation 1, 2, 3, 4, 5, 6 or 7). Part 8 of the study is optional, might be performed, depending on the interim results of prior parts. One of the concept formulations might be re-evaluated under different feeding conditions.
Panel 1EXPERIMENTALParticipants will receive a single 250 milligram (mg) dose of JNJ-53718678 on Day 1 and 200 mg itraconazole once a day on Days 4 to 11 along with a single 250-mg dose of JNJ-53718678 on Day 9.
Panel 2EXPERIMENTALParticipants will receive a single 500-mg dose of JNJ-53718678 on Day 1; a single 600-mg dose of rifampicin along with a single 500-mg dose of JNJ-53718678 on Day 4 and 600 mg rifampicin once daily on Days 5 to 11 along with a single 500-mg dose of JNJ-53718678 on Day 9.
JNJ 53718678 250 milligram (mg)EXPERIMENTALParticipants will receive either single oral dose of 250 mg of JNJ 53718678 or matching placebo on Day 1.
JNJ 53718678 500 mgEXPERIMENTALParticipants will receive either single oral dose of 500 mg of JNJ 53718678 or matching placebo on Day 1.
JNJ 53718678 1000 mgEXPERIMENTALParticipants will receive either single oral dose of 1000 mg of JNJ 53718678 or matching placebo on Day 1.
Interventions
NameTypeDescription
JNJ-53718678DRUGJNJ-53718678 suspension will be administered orally as per assigned treatment sequence.
JNJ-64417184DRUGJNJ-64417184 tablet will be administered orally as per assigned treatment sequence.
JNJ-53718678, 2000 mgDRUGParticipants will be administered JNJ-53718678, 2000 mg as oral suspension in Part 1 (Panel 1).
JNJ-53718678, 3000 mgDRUGParticipants will be administered JNJ- 53718678, 3000 mg as oral suspension in Part 1 (Panel 2).
JNJ-53718678, 4500 mg or Dose to be decidedDRUGParticipants will be administered JNJ-53718678, 4500 mg as oral suspension in Part 1 (Panel 3). If this dose is considered safe and tolerable and if pharmacokinetic data require further dose escalation, then participants will receive JNJ-53718678 (Dose to be decided) in Part 1 (Panel 4). This dose (either from Panel 3 or Panel 4 ) will be used in Part 2 (Dose may be lower/higher based on review of safety, tolerability, and PK data obtained in Part 1).
JNJ-53718678 500 mgDRUGParticipants will be administered JNJ-53718678, 500 mg as oral suspension in Part 2.
JNJ-53718678 PlaceboDRUGParticipants will be administered JNJ-53718678 matching placebo in Part 1 and 2.
Moxifloxacin 400 mgDRUGParticipants will be administered moxifloxacin 400 mg as capsule in Part 2.
Moxifloxacin PlaceboDRUGParticipants will be administered moxifloxacin matching placebo in Part 2.
ItraconazoleDRUGParticipants will receive itraconazole 200 mg (2 capsules of 100 mg) from Day 4-11.
RifampicinDRUGParticipants will receive 600 mg rifampicin (2 capsules of 300 mg) from Day 4-11.
JNJ 53718678DRUGJNJ 53718678 will be orally administered once in a dose of 250, 500 or 1000 mg on Day 1.
PlaceboDRUGPlacebo matching to JNJ 53718678 will be orally administered once on Day 1.
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Eligibility Criteria
Age Range18 Years — 55 Years
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m\^2), extremes included, and body weight not less than (\<) 50 kg at screening * Healthy on the basis of physical examination (including skin examination), medical and surgical history, and vital signs ...

Countries:NetherlandsBelgiumUnited StatesUnited Kingdom
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