Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
JNJ-54861911 · 11 trials · 3 indications
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
The Cmax is the maximum observed concentration.
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
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.
The Cmax is the maximum observed plasma concentration.
The Cmin is the minimum observed plasma concentration.
The Tmax is time to reach the maximum observed plasma concentration.
The AUCtau is a measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
The Cmax is the maximum observed plasma concentration of JNJ-54861911.
The Tmax is the time to reach the maximum observed plasma concentration of JNJ-54861911.
The AUC (0-t) calculated by trapezoidal summation \[time t is the time of the last quantifiable concentration (C\[last\])\].
The AUC (0-24hrs) is the area under the plasma concentration-time curve from 0 to 24 hours post dosing.
The AUC (0-infinity) is the area under the plasma JNJ-54861911concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma JNJ-54861911 concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed quantifiable concentration and lambda(z) is elimination rate constant.
The Lambda (z) determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.
The t(1/2) is defined as 0.693/Lambda (z).
Relative bioavailability, calculated as individual Cmax and AUC treatment ratios (for the comparison of food effect).
The Tmax is time to reach the maximum observed plasma concentration.
The Tlast is time to last observed quantifiable plasma concentration (Clast).
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUC (0-last) and Clast/lambda(z), where AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
The AUC (0-24) is area under the plasma concentration-time curve from time zero to time 24 hours.
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, is calculated as 0.693 divided by lambda(z), where lambda(z) is first-order rate constant associated with the terminal portion of the curve. The t1/2 is the measure of time, for plasma concentration to decrease by one half.
Lambda(z) is first-order elimination rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
The Cmax is the maximum observed plasma concentration.
The Tmax is time to reach the maximum observed plasma concentration.
The Tlast is time to last observed quantifiable plasma concentration (Clast).
The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time, calculated as the sum of AUC (0-last) and Clast/lambda(z), where AUC (0-last) is area under the plasma concentration-time curve from time zero to last quantifiable time; Clast is the last observed quantifiable concentration; and lambda(z) is first-order rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
Area under the plasma concentration-time curve from time zero to time 24 hours.
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve, is calculated as 0.693 divided by lambda(z), where lambda(z) is first-order rate constant associated with the terminal portion of the curve. The t1/2 is the measure of time, for plasma concentration to decrease by one half.
Lambda(z) is first-order elimination rate constant associated with the terminal portion of the semilogarithmic drug concentration-time curve.
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 14 days after last dose administration, that were absent before treatment or that worsened relative to pretreatment state.
The Cmax is the maximum observed plasma concentration.
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.
Cmax is the observed maximum plasma concentration of study drug, taken directly from the plasma concentration-time profile
Time when Cmax is observed, taken directly from the plasma concentration-time profile
Area under the plasma concentration-time curve from 0 to t hours post dosing (time t is the dosing interval)
Elimination half-life associated with the terminal slope of the semi-logarithmic drug concentration-time curve, calculated as 0.693/terminal slope
Rate of absorption will be measured using the peak concentration of JNJ-54861911 (following administration of solid dosage form and suspension dosage form) under fasted conditions and fed conditions.
Extent of absorption will be measured under fasted conditions and fed conditions, using the area under plasma concentrations of JNJ-54861911 versus time from time 0 to the last sample point (AUC\[0-t\]) and from time 0 to infinity (AUC\[0-inf\]).
The maximal tolerated dose (MTD) after single dose administration of JNJ-54861911 or the safety and tolerability at the maximum feasible dose level, whichever is reached first
| Arm | Type | Description |
|---|---|---|
| Treatment Group 1 | EXPERIMENTAL | Participants will self-administer JNJ-54861911, two tablets of 5 milligram (mg) each for a total of 10 mg, orally, once daily, from Day 1 until Month 6. |
| Treatment Group 2 | EXPERIMENTAL | Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6. |
| Placebo | PLACEBO_COMPARATOR | Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6. |
| Panel 1 | EXPERIMENTAL | Participant will be administered a single oral dose of rosuvastatin 10 milligram (mg) on Day 1 and Day 14 and JNJ-54861911 at a dose of 25 mg once daily from Day 8 until Day 17. |
| Panel 2 | EXPERIMENTAL | Participant will be administered a single oral dose of metformin 500-mg on Day 1 and Day 14 and JNJ-54861911 at a dose of 25 mg once daily from Day 8 until Day 16. |
| JNJ-54861911, 10 mg | EXPERIMENTAL | JNJ-54861911, 10 milligram (mg) (2\*5 mg tablet) orally once daily for 4 weeks. |
| JNJ-54861911, 50 mg | EXPERIMENTAL | JNJ-54861911, 50 mg (2\*25 mg tablet) orally once daily for 4 weeks. |
| Sequence 1 (ABC) | EXPERIMENTAL | Participants will receive Treatment A (single dose of JNJ-54861911 25 milligram \[mg\] formulation 1 \[reference\] under fasted conditions) in Period 1; followed by Treatment B (single oral dose of JNJ-54861911 25 mg formulation 2 \[test\] under fasted conditions) in Period 2; followed by Treatment C (single oral dose of JNJ-54861911 25 mg formulation 2 under fed conditions) in Period 3. A washout period of at least 7 days will be maintained between each treatment period. |
| Sequence 2 (ACB) | EXPERIMENTAL | Participants will receive Treatment A in Period 1; followed by Treatment C in Period 2; followed by Treatment B in Period 3. A washout period of at least 7 days will be maintained between each treatment period. |
| Sequence 3 (BAC) | EXPERIMENTAL | Participants will receive Treatment B in Period 1; followed by Treatment A in Period 2; followed by Treatment C in Period 3. A washout period of at least 7 days will be maintained between each treatment period. |
| Sequence 4 (BCA) | EXPERIMENTAL | Participants will receive Treatment B in Period 1; followed by Treatment C in Period 2; followed by Treatment A in Period 3. A washout period of at least 7 days will be maintained between each treatment period. |
| Sequence 5 (CAB) | EXPERIMENTAL | Participants will receive Treatment C in Period 1; followed by Treatment A in Period 2; followed by Treatment B in Period 3. A washout period of at least 7 days will be maintained between each treatment period. |
| Sequence 6 (CBA) | EXPERIMENTAL | Participants will receive Treatment C in Period 1; followed by Treatment B in Period 2; followed by Treatment A in Period 3. A washout period of at least 7 days will be maintained between each treatment period. |
| JNJ-54861911 + Caffeine + Midazolam +Tolbutamide | EXPERIMENTAL | JNJ-54861911, 50 milligram (mg) (2\*25 mg tablets) orally once daily from Day 2 to Day 9 along with caffeine 100 mg (2\*50 mg tablets), midazolam 2 mg (1 milliliter \[mL\], 2 mg/mL solution), and tolbutamide 500 mg tablet, orally on Day 1, 2, and 9. |
| Itraconazole + JNJ-54861911 (Part 1) | EXPERIMENTAL | Single dose of JNJ-54861911, 25 milligram (mg) tablet orally on Day 1 and Day 9 along with itraconazole 200 mg (2\*100 mg capsule) orally once daily from Day 5 to Day 12. |
| Clarithromycin + JNJ-54861911 (Part 2) | EXPERIMENTAL | Single dose of JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9 along with clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12. |
| Cohort A | EXPERIMENTAL | Single oral dose of either JNJ-54861911, 25 milligram (mg) tablet or matched placebo tablet on Day 1. |
| Cohort B | EXPERIMENTAL | Single oral dose of either JNJ-54861911, 50 mg (2\*25 mg tablets) or matched placebo tablets on Day 1. |
| Cohort C | EXPERIMENTAL | Single oral dose of either JNJ-54861911, 100 mg (4\*25 mg tablets) or matched placebo tablets on Day 1. |
| JNJ-54861911 10 mg | EXPERIMENTAL | From Day 1 to Day 28 inclusive, patients will self-administer once daily study drug (JNJ-54861911 or placebo) with a glass of non-carbonated water (approximately 200 mL). |
| JNJ-54861911 50 mg | EXPERIMENTAL | - |
| Cohort 1: JNJ-54861911 3 mg | EXPERIMENTAL | Participants will be administered single doses of JNJ-54861911 on Days 1 to 14. Initially the doses will be once per day, but the frequency of daily dosing (eg, once-daily, twice-daily, three times daily) may change prior to or during study conduct depending on the pharmacokinetic data from the ongoing single-ascending dose study (54861911ALZ1001) or ongoing cohorts in this current study. Actual dose levels as well as the magnitude of dose escalation will depend on the results of the ongoing single-ascending dose study, the observed safety and tolerability profile as well as the observed exposures. |
| Cohort 2: JNJ-54861911 10 mg | EXPERIMENTAL | - |
| Cohort 3: JNJ-54861911 30 mg | EXPERIMENTAL | - |
| Cohort 4: JNJ-54861911 80 mg | EXPERIMENTAL | - |
| Cohort 5: JNJ-54861911 25 mg | EXPERIMENTAL | - |
| Cohorts 1-4: Placebo | PLACEBO_COMPARATOR | Participants in Cohorts 1-4 will receive matching placebo. |
| Part 1 - Cohort 1: JNJ-54861911 1 mg | EXPERIMENTAL | Following each dose level the observed safety and tolerability profile will be evaluated. The dose will be escalated only if the observed safety and tolerability profile is acceptable. |
| Part 1 - Cohort 2: JNJ-54861911 3 mg | EXPERIMENTAL | - |
| Part 1 - Cohort 3: JNJ-54861911 9 mg | EXPERIMENTAL | - |
| Part 2 - Cohort 4: JNJ-54861911 9 mg | EXPERIMENTAL | - |
| Part 2 - Cohort 5: JNJ-54861911 27 mg | EXPERIMENTAL | - |
| Part 2 - Cohort 6: JNJ-54861911 81 mg | EXPERIMENTAL | - |
| Part 2 - Cohort 7: JNJ-54861911 160 mg | EXPERIMENTAL | - |
| Part 3 - Cohort 8: JNJ-54861911 (dose to be determined [tbd]) | EXPERIMENTAL | - |
| Parts 1 through 3 - Placebo | PLACEBO_COMPARATOR | Participants in each cohort will receive matching placebo. |
| Name | Type | Description |
|---|---|---|
| JNJ-54861911, 10 milligram (mg) | DRUG | Participants will self-administer JNJ-54861911, two tablets of 5 mg each for a total of 10 mg, orally, once daily, from Day 1 until Month 6 in treatment group 1. |
| JNJ-54861911, 50 mg | DRUG | Participants will self-administer JNJ-54861911, two tablets of 25 mg each for a total of 50 mg, orally, once daily, from Day 1 until Month 6 in treatment group 2. |
| Placebo | DRUG | Placebo matched to JNJ-54861911, orally, once daily, from Day 1 until Month 6 in placebo group. |
| Rosuvastatin | DRUG | Rosuvastatin will be administered as a single oral 10 milligram (mg) dose on Day 1 and Day 14. |
| JNJ-54861911 | DRUG | JNJ-54861911 will be administered at a dose of 25 mg once daily from Day 8 to Day 17 (in panel 1), Day 8 to 16 (in panel 2). |
| Metformin | DRUG | Metformin will be administered as a single oral 500 mg on Day 1 and Day 14. |
| JNJ-54861911, 10 mg | DRUG | JNJ-54861911, 10 mg (2\*5 mg tablet) orally once daily for 4 weeks. |
| JNJ-54861911 (Treatment A) | DRUG | Participants will receive a single oral 25 mg formulation 1 of JNJ-54861911 tablet as Treatment A under fasted conditions in one of the treatment periods. |
| JNJ-54861911 (Treatment B) | DRUG | Participants will receive a single oral 25 mg formulation 2 of JNJ-54861911 tablet as Treatment B under fasted conditions in one of the treatment periods. |
| JNJ-54861911 (Treatment C) | DRUG | Participants will receive a single oral 25 mg formulation 2 of JNJ-54861911 tablet as Treatment C under fed conditions in one of the treatment periods. |
| Caffeine | DRUG | Single oral dose of caffeine 100 mg (2\*50 mg tablets), on Day 1, 2, and 9. |
| Midazolam | DRUG | Single oral dose of midazolam 2 mg (1 mL, 2 mg/mL solution), on Day 1, 2, and 9. |
| Tolbutamide | DRUG | Single oral dose of Tolbutamide 500 mg tablet, on Day 1, 2, and 9. |
| JNJ-54861911, 25 mg | DRUG | JNJ-54861911, 25 mg tablet orally on Day 1 and Day 9. |
| Itraconazole 200 mg | DRUG | Itraconazole 200 mg (2\*100 mg capsule) orally once daily from Day 5 to Day 12. |
| Clarithromycin 500 mg | DRUG | Clarithromycin 500 mg immediate release tablet orally twice daily from Day 5 to Day 12. |
| JNJ-54861911 (25 mg) | DRUG | Single oral dose of JNJ-54861911, 25 mg on Day 1. |
| JNJ-54861911 (50 mg) | DRUG | Single oral dose of JNJ-54861911, 50 mg on Day 1. |
| JNJ-54861911 (100 mg) | DRUG | Single oral dose of JNJ-54861911, 100 mg on Day 1. |
| JNJ-54861911 10 mg | DRUG | JNJ-54861911 10 mg will be administered as two 5 mg oral tablets once daily. |
| JNJ-54861911 50 mg | DRUG | JNJ-54861911 50 mg will be administered as two 25 mg oral tablets once daily. |
| JNJ-54861911 3 mg | DRUG | JNJ-54861911 3 mg will be administered as an oral suspension formulation. |
| JNJ-54861911 30 mg | DRUG | JNJ-54861911 30 mg will be administered as an oral suspension formulation. |
| JNJ-54861911 80 mg | DRUG | JNJ-54861911 80 mg will be administered as an oral suspension formulation. |
| JNJ-54861911 25 mg | DRUG | JNJ-54861911 25 mg will be administered as a solid dose formulation. |
| JNJ-54861911 1mg | DRUG | JNJ-54861911 1 mg will be administered as a single oral dose after an overnight fast of at least 10 hours. |
| JNJ-54861911 9 mg | DRUG | JNJ-54861911 9 mg will be administered as a single oral dose. |
| JNJ-54861911 27 mg | DRUG | JNJ-54861911 27 mg will be administered as a single oral dose. |
| JNJ-54861911 81 mg | DRUG | JNJ-54861911 81 mg will be administered as a single oral dose. |
| JNJ-54861911 160 mg | DRUG | JNJ-54861911 160 mg will be administered as a single oral dose. |
| JNJ-54861911 tbd | DRUG | The dose of JNJ-54861911 will be derived from the results obtained in Parts 1 and 2. |
Inclusion Criteria: * Participants in the early alzheimer's disease (AD) spectrum must have a global Clinical Dementia Rating Scale( CDR) score of 0 (asymptomatic at risk for AD) to 0.5 prodromal AD (pAD) inclusive * Participants must have evidence of amyloid pathology by means of either: a) low Ce...
Top 20 of 24 competitors
JNJ-54861911 is an investigational small molecule being studied for Alzheimer's disease. It has been evaluated in clinical trials involving healthy volunteers and patients with prodromal Alzheimer's disease. The drug is in Phase 1 clinical development and is not yet approved by regulatory authorities.
JNJ-54861911 is being developed by Johnson & Johnson, a company traded on the New York Stock Exchange under the ticker symbol JNJ. The drug is an investigational small molecule in Phase 1 clinical development for Alzheimer's disease.
JNJ-54861911 is in Phase 1 clinical development. All eight clinical trials for the drug have been completed, with no active trials currently ongoing. The drug remains investigational and has not received regulatory approval for any indication.
JNJ-54861911 has been studied in several completed Phase 1 trials. NCT01827982 and NCT01887535 evaluated safety and tolerability in healthy volunteers. NCT01978548 assessed effects on amyloid beta processing in patients with prodromal Alzheimer's disease. NCT02211079 examined drug interactions with cytochrome P450 substrates.
JNJ-54861911 is a small molecule designed to affect amyloid beta processing in the brain. In clinical trials, researchers measured its effects on amyloid beta levels in cerebrospinal fluid and plasma of patients with prodromal Alzheimer's disease, indicating the drug targets pathways involved in amyloid beta production or clearance.