Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Seltorexant · 7 trials · 3 indications
The NPI-12, measure of psychobehavioral disturbances assessed frequency and severity of disturbances in 12 domains, based on a caregiver interview. Frequency for each domain was rated on a 4-point scale (from 1=rarely to 4=very often) and severity on a 3-point scale (from 1=mild to 3=severe), with the score for each domain being product of frequency and severity scores, such that each domain was scored from 1 to 12. The NPI-12 total score was the sum of 12 domain scores, ranging from 0 (best) to 144 (worst), higher score represented greater frequency and worst severity of the symptoms. NPI-C was an instrument developed on basis of original NPI that gives a score based on product of frequency and severity ratings of 12 symptom domains that were summed to a total score. NPI-C domains: agitation and aggression NPI-C A+A were scored based on both caregiver and participant interviews and score ranged from 0 (does not occur) to 63 (severe). Higher scores indicated more severity.
The NPI-12, measure of psychobehavioral disturbances assessed frequency and severity of disturbances in 12 domains, based on a caregiver interview. Frequency for each domain was rated on a 4-point scale (from 1=rarely to 4=very often) and severity on a 3-point scale (from 1=mild to 3=severe), with the score for each domain being product of frequency and severity scores, such that each domain was scored from 1 to 12. The NPI-12 total score was the sum of 12 domain scores, ranging from 0 (best) to 144 (worst), higher score represented greater frequency and worst severity of the symptoms. NPI-C was an instrument developed on the basis of original NPI that gives a score based on product of frequency and severity ratings of 12 symptom domains that were summed to a total score. NPI-C domains: agitation and aggression NPI-C A+A were scored based on both caregiver and participant interviews and score ranged from 0 (does not occur) to 63 (severe). Higher scores indicated more severity.
Absolute bioavailability is calculated as the ratio of dose normalized area under the plasma drug concentration-time curve (AUC) of oral and intravenous (IV) administration.
Cmax is defined as the maximum observed plasma concentration of seltorexant and its metabolites.
Clast is defined as the last observed measurable (non-below quantification limit \[non-BQL\]) plasma concentration of seltorexant and its metabolites.
Tmax is defined as the actual sampling time to reach the maximum observed plasma concentration of seltorexant and its metabolites.
AUC (0-last) is defined as area under the plasma concentration-time curve from the time of dosing to the last measurable plasma concentration of seltorexant and its metabolites.
AUC (0-infinity) is defined as area under the plasma concentration-time curve of seltorexant and its metabolites extrapolated to infinity, calculated using the linear trapezoidal method from time zero to infinite time calculated as the sum of AUC(0-last)+C(last)/ lambda(z).
Apparent elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve of seltorexant and its metabolites.
AHI score is used to indicate the severity of sleep apnea. The AHI is calculated by dividing the number of apnea events by the number of hours of sleep. The AHI values for adults are categorized as: Normal: AHI less than (\<)5, Mild sleep apnea: 5 less than or equal to (\<=) AHI \<15, Moderate sleep apnea: 15\<= AHI \<30, and Severe sleep apnea: AHI greater than or equal to (\>=)30.
Cmax is the maximum observed plasma concentration.
AUC(0-last) is the area under the plasma concentration-time curve from the time of dosing to the last measurable plasma concentration.
AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated using the observed value of the last non-zero plasma concentration.
Change from baseline in QT and QTc interval will be assessed. QT interval will be measured in triplicates from 12 lead Holter extracted triplicate ECG recordings and corrected QT (QTc) interval will be calculated based on Fridericia (QTcF), Bazett (QTcB), and/or study specific power (QTcP) equations.
The percentage of participants in each treatment having T-wave morphology changes from baseline that represent the appearance or worsening of the morphological abnormality will be reported.
The percentage of participants with change from baseline with abnormal U-waves morphology that represent the appearance or worsening of the morphological abnormality will be reported.
Cmax is the maximum observed plasma concentration and will be evaluated when compared for 3 oral tablet formulations of seltorexant in fasted and semi-fasted conditions.
AUC (0-last) is the area under the plasma concentration-time curve from the time of study drug administration to the last measurable plasma concentration and will be evaluated when compared for 3 oral tablet formulations of seltorexant in fasted and semi-fasted conditions.
AUC (0-infinity) is the is the area under the plasma concentration-time curve from time zero to infinite time, calculated using the observed value of the last non-zero plasma concentration and will be evaluated when compared for 3 oral tablet formulations of seltorexant in fasted and semi-fasted conditions.
Relative bioavailability is the percentage of the administered dose that is systemically available, calculated as: (AUC \[0-infinity\] of test divided by AUC \[0-infinity\] of reference) multiplied by 100, where the reference treatment is a non-intravenous administration. Relative bioavailability will be evaluated when compared for 3 oral tablet formulations of seltorexant in fasted and semi-fasted conditions.
| Arm | Type | Description |
|---|---|---|
| Seltorexant | EXPERIMENTAL | Participants will receive single oral dose of seltorexant 20 milligrams (mg) tablet once daily from Day 1 to Day 42. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive single oral dose of matching placebo tablet once daily from Day 1 to Day 42. |
| Treatment Sequence ABC | EXPERIMENTAL | Participants will receive a single dose of seltorexant as formulation (Test 1) (Treatment A) in Treatment Period 1, followed by a single dose of seltorexant as formulation (Test 2) (Treatment B) in Treatment Period 2, followed by a single dose of seltorexant as formulation (Reference) (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period under fasted condition. There will be a washout period of 7 to 14 days from dosing on Day 1 of each Treatment Period. |
| Treatment Sequence BCA | EXPERIMENTAL | Participants will receive Treatment B in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment A in Treatment Period 3 on Day 1 of each Treatment Period under fasted condition. There will be a washout period of 7 to 14 days from dosing on Day 1 of each Treatment Period. |
| Treatment Sequence CAB | EXPERIMENTAL | Participants will receive Treatment C in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment B in Treatment Period 3 on Day 1 of each Treatment Period under fasted condition. There will be a washout period of 7 to 14 days from dosing on Day 1 of each Treatment Period. |
| Treatment Sequence CBA | EXPERIMENTAL | Participants will receive Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment A in Treatment Period 3 on Day 1 of each Treatment Period under fasted condition. There will be a washout period of 7 to 14 days from dosing on Day 1 of each Treatment Period. |
| Treatment Sequence ACB | EXPERIMENTAL | Participants will receive Treatment A in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment B in Treatment Period 3 on Day 1 of each Treatment Period under fasted condition. There will be a washout period of 7 to 14 days from dosing on Day 1 of each Treatment Period. |
| Treatment Sequence BAC | EXPERIMENTAL | Participants will receive Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment C in Treatment Period 3 on Day 1 of each Treatment Period under fasted condition. There will be a washout period of 7 to 14 days from dosing on Day 1 of each Treatment Period. |
| Seltorexant Followed by Placebo | EXPERIMENTAL | Participants will receive seltorexant (40 milligram \[mg\] capsules) once daily for 4 consecutive days, and after a washout period of 7 to 10 days, participants will receive matching placebo orally once daily for 4 consecutive days. |
| Placebo Followed by Seltorexant | EXPERIMENTAL | Participants will receive placebo once daily for 4 consecutive days, and after a washout period of 7 to 10 days, participants will receive seltorexant (40 mg capsules) orally once daily for 4 consecutive days. |
| Part 1: Seltorexant High Dose | EXPERIMENTAL | In Part 1, participants will receive the following treatments: Treatment A: Two low doses of seltorexant tablets (reference formulation), Treatment B: High dose of seltorexant tablet (Test formulation 1), Treatment C: High dose of seltorexant tablet (Test formulation 2), Treatment D: Two low doses of seltorexant tablets (Test formulation 3), Treatment E: Two low doses of seltorexant tablets (Test formulation 4), Treatment F: Two low doses of seltorexant tablets (Test formulation 5), as one of 6 possible treatment sequences on Day 1 in each treatment Periods (Period 1-6). There will be a washout Period of 7 to 14 days from dosing on Day 1 of each treatment period. |
| Part 2: Seltorexant High Dose | EXPERIMENTAL | Participants will receive the following treatments: Treatment G: Two low doses of seltorexant tablets (Reference formulation), Treatment H: High dose or two low doses of seltorexant tablet (Test formulation 1), Treatment I: High dose of seltorexant tablet (Test formulation 2), as one of 6 possible treatment sequences on Day 1 in each treatment Periods (Period 1-3). There will be a washout period of 7 to 14 days from dosing on Day 1 of each treatment period. |
| Part 3: Seltorexant Low Dose or High Dose | EXPERIMENTAL | Part 3 will have 3 subparts (Part 3A, Part 3B, and Part 3C). In Part 3A and 3B, participants will receive high dose of seltorexant (selected formulation 6) and two low doses of seltorexant (selected formulation 7) respectively in a different food conditions on Day 1 in each treatment Periods (Periods 1-5). In Part 3C, participants will receive high dose of seltorexant (selected formulation 6) and two low doses of seltorexant (selected formulation 7 ) on Day 1 in each period (Period 1 and 2). There will be a washout period of 7 to 14 days from dosing on Day 1 of each treatment period. |
| Seltorexant (Low and high dose) | EXPERIMENTAL | Participants will receive seltorexant tablets orally in 2 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period. |
| Moxifloxacin | EXPERIMENTAL | Participants will receive moxifloxacin tablets orally in 1 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period. |
| Placebo Matched to Seltorexant | EXPERIMENTAL | Participants will receive seltorexant placebo tablets orally in 3 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period. |
| Placebo Matched to Moxifloxacin | EXPERIMENTAL | Participants will receive moxifloxacin placebo tablets orally in 3 of 4 treatment arms (A,B,C,D) in a cross-over design, with 7 days wash-out phase between each treatment period. |
| Part 1 | EXPERIMENTAL | In Part 1, all participants will receive a single oral dose of seltorexant (40 milligram \[mg\]) in all the 6 treatments as Treatment A (Formulation 1 in fasted state), B (Formulation 1 in semi-fasted state), C (Formulation 2 in fasted state), D (Formulation 2 in semi-fasted state), E (Formulation 3 in fasted state) and F (Formulation 3 in semi-fasted state) and the participants will be assigned to one of the 8 sequences (that is, ADBCEF, ADBCFE, BACDEF, BACDFE, CBDAEF, CBDAFE, DCABEF, DCABFE). A washout period of at least 7 days between subsequent study drug administrations on Day 1 of each treatment period will be maintained. |
| Part 2 (Optional) | EXPERIMENTAL | Optional Part 2 will only be performed if considered to be warranted by the sponsor based on the preliminary pharmacokinetic (PK) analysis of the results from Part 1. Participants will receive a single oral dose of seltorexant (20 mg) as 3 different formulations assigned to one of the either 6 or 4 treatment sequences under fasted or semi-fasted conditions. The treatment will be assigned in 1 of the 6 or 4 assigned sequences per treatment period that is either Period 1 to 6 or Period 1 to 4). |
| Name | Type | Description |
|---|---|---|
| Seltorexant | DRUG | Seltorexant 20 mg will be administered orally as a tablet. |
| Placebo | DRUG | Matching placebo will be administered orally as a tablet. |
| Seltorexant 40 mg | DRUG | Seltorexant 40 mg capsules (over-encapsulated tablets) will be administered orally. |
| Seltorexant High Dose | DRUG | In Part 1, Part 2, and Part 3 (3A and 3C), Seltorexant high dose (either a high dose tablet or two low dose tablets) will be administered orally. |
| Seltorexant Low Dose | DRUG | In Part 3 (3B and 3C), Seltorexant low dose will be administered orally. |
| Placebo Matched to Seltorexant | OTHER | Participants will be administered matching placebo to seltorexant tablets on Day 1. |
| Placebo Matched to Moxifloxacin | OTHER | Participants will be administered oral dose of moxifloxacin placebo tablet on Day 1. |
| Moxifloxacin Dose 1 | DRUG | Participants will be administered oral dose 1 of moxifloxacin on Day 1. |
| Seltorexant 20 mg | DRUG | Seltorexant as a tablet of 20 mg will be administered as Formulation 1, 2 and 3 orally in Part 2. |
Inclusion Criteria: * Participant has received a diagnosis of probable Alzheimer Disease (AD) (Diagnostic and Statistical Manual of Mental Disorders-5 \[DSM-5\]) with the following characteristics at screening: Clinical Dementia Rating (CDR) global score greater than or equal to (\>=) 1; Mini-Menta...
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Seltorexant is an investigational small molecule being developed for major depressive disorder, obstructive sleep apnea, and Alzheimer disease. It is also studied in healthy participants for bioavailability, cardiac safety, and pharmacokinetic assessments. The drug is in Phase 2 clinical development and is not approved by the FDA.
Seltorexant is being developed by Johnson & Johnson, a company traded on the NYSE under the ticker JNJ. The drug is in Phase 2 clinical trials for neurological conditions including major depressive disorder, obstructive sleep apnea, and Alzheimer disease.
Seltorexant is in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The development program includes completed Phase 1 trials in healthy participants and ongoing studies in patient populations with major depressive disorder, obstructive sleep apnea, and Alzheimer disease.
Seltorexant has been studied in several clinical trials, including NCT03438461, NCT03494907, NCT03682380, and NCT05236868. These are Phase 1 studies in healthy participants that have been completed. The drug is also being evaluated in Phase 2 trials for major depressive disorder, obstructive sleep apnea, and Alzheimer disease.
Yes, Seltorexant is also known as JNJ-42847922. Clinical trial records use both names interchangeably, with some studies titled 'A Study of Seltorexant (JNJ-42847922)' to clarify the identity of the investigational drug.