Clinical Trials List
Protocol Number42847922MDD3001
NCT Number(ClinicalTrials.gov Identfier)NCT04533529
2020-04-10 - 2024-12-31
Phase III
Not yet recruiting5
Recruiting2
ICD-10F33.3
Major depressive disorder, recurrent, severe with psychotic symptoms
A Multicenter, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients with Major Depressive Disorder with Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy and an Open-labeled Long-term Safety Extension Treatment with Seltorexant
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Janssen Research & Development, LLC
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 胡力予 Division of Psychiatry
- Ya-Mei Bai Division of Psychiatry
- Cheng-Ta Li Division of Psychiatry
- 鄭智銘 Division of Psychiatry
- 胡力允 Division of Psychiatry
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- HUNG-KUANG SU Division of Psychiatry
- YI-TING LIN Division of Psychiatry
- 謝明憲 無
- 徐勝駿 Division of Psychiatry
- 陳宜明 Division of Psychiatry
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 鍾國軒 Division of Psychiatry
- HSIN-CHIEN LEE 無
- Kuo-Hsuan Chung Division of Psychiatry
- Yu-Jui Huang Division of Psychiatry
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Major Depressive Disorder
Objectives
The purpose of this study is to assess the efficacy of seltorexant compared with placebo as adjunctive therapy to an antidepressant in improving depressive symptoms in participants with major depressive disorder with insomnia symptoms (MDDIS) who have had an inadequate response to current antidepressant therapy with an selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in double-blind treatment phase and to assess the long-term safety and tolerability of seltorexant as adjunctive therapy to an antidepressant in participants with major depressive disorder (MDD) in open-label treatment phase.
Test Drug
Seltorexant
Active Ingredient
Seltorexant
Dosage Form
tablet
Dosage
20 mg/tablet
Endpoints
Primary Outcome Measures :
Double-blind (DB) Treatment Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline, Day 43 ]
MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Open-Label (OL) Treatment Phase: Number of Participants with Adverse Events (AEs) including AEs of Special Interest (AESI) as a Measure of Safety and Tolerability [ Time Frame: 1 year ]
Number of participants with AE including AE of special interest as a measure of safety and tolerability will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. AESI will comprise of cataplexy, sleep paralysis, complex, sleep-related behaviors/parasomnias, sleep terrors, bruxism, sleep sex, sleep related eating disorder, catathrenia, fall and motor vehicle accident.
OL Treatment Phase: Change From Baseline in Blood Pressure [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in blood pressure will be reported.
OL Treatment Phase: Change From Baseline in Pulse Rate [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in pulse rate will be reported.
OL Treatment Phase: Change From Baseline in Weight [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in weight as a part of physical examination will be reported.
OL Treatment Phase: Change From Baseline in Body Mass Index (BMI) [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in BMI as a part of physical examination will be reported.
OL Treatment Phase: Change From Baseline in Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in suicidality assessment using C-SSRS will be reported. C-SSRS is a clinician rated assessment of suicidal behavior and/or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses are listed. Worsening of suicidal ideation indicates an increase in severity of suicidal ideation from baseline. Suicidal behavior consists of 5 'yes/no' items: preparatory acts or behavior, aborted attempt, actual attempt, completed suicide.
OL Treatment Phase: Physician Withdrawal Checklist (PWC-20) Scores [ Time Frame: End of Treatment/Early withdrawal to end of the Follow-up visit (up to 14 days) ]
Withdrawal symptoms assessment using the PWC-20 will be reported. The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition.
OL Treatment Phase: Number of Participants with Laboratory Abnormalities [ Time Frame: Up to 1 year ]
Number of participants with laboratory abnormalities related to hematology, serum chemistry, coagulation, liver function tests and urinalysis will be reported.
OL Treatment Phase: Change From Baseline in QTc Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiogram (ECG).
OL Treatment Phase: Change from Baseline in Heart Rate (HR) [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in HR will be measured by ECG.
OL Treatment Phase: Change from Baseline in QRS Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in QRS interval will be measured by ECG.
OL Treatment Phase: Change from Baseline in PR Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in PR interval will be measured by ECG.
OL Treatment Phase: Change From Baseline in QT Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in QT interval will be measured by ECG.
OL Treatment Phase: Participant-reported Sexual Functioning Using Arizona Sexual Experiences Scale (ASEX) Score [ Time Frame: Up to 1 year ]
The ASEX is a patient-reported 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. The total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.
Double-blind (DB) Treatment Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score [ Time Frame: Baseline, Day 43 ]
MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Open-Label (OL) Treatment Phase: Number of Participants with Adverse Events (AEs) including AEs of Special Interest (AESI) as a Measure of Safety and Tolerability [ Time Frame: 1 year ]
Number of participants with AE including AE of special interest as a measure of safety and tolerability will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. AESI will comprise of cataplexy, sleep paralysis, complex, sleep-related behaviors/parasomnias, sleep terrors, bruxism, sleep sex, sleep related eating disorder, catathrenia, fall and motor vehicle accident.
OL Treatment Phase: Change From Baseline in Blood Pressure [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in blood pressure will be reported.
OL Treatment Phase: Change From Baseline in Pulse Rate [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in pulse rate will be reported.
OL Treatment Phase: Change From Baseline in Weight [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in weight as a part of physical examination will be reported.
OL Treatment Phase: Change From Baseline in Body Mass Index (BMI) [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in BMI as a part of physical examination will be reported.
OL Treatment Phase: Change From Baseline in Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in suicidality assessment using C-SSRS will be reported. C-SSRS is a clinician rated assessment of suicidal behavior and/or intent. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 'yes/no' items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Only items with yes responses are listed. Worsening of suicidal ideation indicates an increase in severity of suicidal ideation from baseline. Suicidal behavior consists of 5 'yes/no' items: preparatory acts or behavior, aborted attempt, actual attempt, completed suicide.
OL Treatment Phase: Physician Withdrawal Checklist (PWC-20) Scores [ Time Frame: End of Treatment/Early withdrawal to end of the Follow-up visit (up to 14 days) ]
Withdrawal symptoms assessment using the PWC-20 will be reported. The PWC-20 is a simple and accurate method used to assess potential withdrawal symptoms following cessation of treatment. The PWC-20 is a reliable and sensitive instrument for the assessment of discontinuation symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition.
OL Treatment Phase: Number of Participants with Laboratory Abnormalities [ Time Frame: Up to 1 year ]
Number of participants with laboratory abnormalities related to hematology, serum chemistry, coagulation, liver function tests and urinalysis will be reported.
OL Treatment Phase: Change From Baseline in QTc Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in QT interval corrected for heart rate (QTc interval) using Fridericia method will be measured by electrocardiogram (ECG).
OL Treatment Phase: Change from Baseline in Heart Rate (HR) [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in HR will be measured by ECG.
OL Treatment Phase: Change from Baseline in QRS Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in QRS interval will be measured by ECG.
OL Treatment Phase: Change from Baseline in PR Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in PR interval will be measured by ECG.
OL Treatment Phase: Change From Baseline in QT Interval [ Time Frame: Baseline (Day 43), up to 1 year ]
Change from baseline in QT interval will be measured by ECG.
OL Treatment Phase: Participant-reported Sexual Functioning Using Arizona Sexual Experiences Scale (ASEX) Score [ Time Frame: Up to 1 year ]
The ASEX is a patient-reported 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. The total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.
Inclution Criteria
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Male or female, aged 18 to 74 years (inclusive).
Note: Participants should be at least 18 years of age or older as per the legal age of consent
in the jurisdiction in which the study is taking place.
2. Meet DSM-5 diagnostic criteria for MDD, without psychotic features (DSM-5 296.22,
296.23, 296.32, or 296.33), based upon clinical assessment and confirmed by the
SCID-CT diagnosed with first depressive episode prior to age 60. The length of the
current depressive episode must be ≤18 months.
3. Have had an inadequate response to at least 1 but no more than 2 antidepressants (see the
inclusion criterion 4 below), administered at an adequate dose and duration in the current
episode of depression. The current antidepressant cannot be the first antidepressant
treatment for the first lifetime episode of depression. An inadequate response is defined
as <50% reduction but with some improvement in depressive symptom severity with
residual symptoms present other than insomnia, and overall good tolerability, as assessed
by the MGH-ATRQ. An adequate trial is defined as an antidepressant treatment for at
least 6 weeks (and no greater than 12 months in the current episode) at or above the stable
therapeutic dose specified in the MGH-ATRQ, must include the participant’s current
antidepressant treatment. Note: Participants with no improvement on the current
SSRI/SNRI should not be enrolled in the study. If the participant has received
2 SSRI/SNRI treatments of sufficient dose and duration in the current episode, and has
shown <25% improvement to both, then the participant would not qualify based on
exclusion criterion 9.
4. Is receiving and tolerating well any one of the following SSRI or SNRI for depressive
symptoms, in any formulation and available in the participating country: citalopram,
duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran,
paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable
dose (at therapeutic dose level) for at least 6 weeks, and for no greater than 12 months in
the current episode, at screening.
Note: Dose and duration of treatment should be documented in the source documents by
the investigator based on available evidence such as using the medical or pharmacy
records. The investigator will use this information to complete the MGH-ATRQ.
Note: Participants using fluvoxamine as baseline SSRI and have normal renal and hepatic
function may enter the study. See renal and hepatic function restrictions in Section 6.5
(Concomitant Therapy).
5. Have a HDRS-17 total score ≥22 at screening and must not demonstrate a clinically
significant improvement (ie, an improvement of >20% on their HDRS-17 total score)
from the beginning to end of screening (from the first to the second independent HDRS17 rating), so long as the HDRS-17 total score is ≥18 at the end of screening (Day -5 to -
2 visit).
6. Body mass index (BMI) between 18 and 37 kg/m2
inclusive (BMI=weight/height2).
7. Must be an outpatient at screening.
8. Participant must be medically stable on the basis of the following performed at screening:
physical examination, vital signs (including blood pressure), and 12-lead ECG performed
at screening and baseline. If there are any abnormalities that are not specified in the
inclusion and exclusion criteria, their clinical significance must be determined by the
investigator and recorded in the participant's source documents and initialed by the
investigator.
9. Participant must be medically stable on the basis of clinical laboratory tests performed at
screening. If the results of the serum chemistry panel, hematology, or urinalysis are
outside the normal reference ranges, the participant may be included only if the
investigator judges the abnormalities or deviations from normal to be not clinically
significant or to be appropriate and reasonable for the population under study. This
determination must be recorded in the participant's source documents and initialed by the
investigator.
10. Must sign an ICF indicating that he or she understands the purpose of and procedures
required for the study and be willing to participate in the study.
11. A woman of childbearing potential must have a negative highly sensitive serum (β human
chorionic gonadotropin [β-hCG]) pregnancy test at screening and a negative urine
pregnancy test predose on Day 1 of the DB phase prior to randomization.
12. Contraceptive use by men or women should be consistent with local regulations regarding
the use of contraceptive methods for participants in clinical studies.
a. Before entering the study, a woman must be either:
Postmenopausal
A postmenopausal state is defined as no menses for 12 months without an
alternative medical cause. A high follicle stimulating hormone (FSH) level in the
postmenopausal range based on the reference range of the central laboratory
may be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy, however in the absence of
12 months of amenorrhea, a single FSH measurement is insufficient.
Permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy,
bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
b. Of childbearing potential and
Practicing a highly effective method of contraception (failure rate of <1% per year
when used consistently and correctly) (see Section 10.5, Appendix 5,
Contraceptive and Barrier Guidance and Collection of Pregnancy Information).
The investigator should evaluate the potential for contraceptive method failure
(eg, noncompliance, recently initiated) in relationship to the first dose of study
intervention.
Examples of highly effective contraceptives include:
− User independent methods:
implantable progestogen-only hormone contraception associated with
inhibition of ovulation; intrauterine device (IUD); intrauterine hormonereleasing system (IUS); vasectomized partner; sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining
from heterosexual intercourse during the entire period of risk associated with
the study drug. The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the study and the preferred and usual lifestyle of the
participant.)
− User-dependent methods:
combined (estrogen- and progestogen-containing) hormonal contraception
associated with inhibition of ovulation: oral, intravaginal, and transdermal;
progestogen-only hormone contraception associated with inhibition of
ovulation: oral and injectable
Typical use failure rates may differ from those when used consistently and
correctly. Use should be consistent with local regulations regarding the use of
contraceptive methods for participants in clinical studies
Agrees to remain on a highly effective method throughout the study and for at
least 1 month after the last dose of study drug.
Note: If the childbearing potential status changes after start of the study or the risk of
pregnancy changes (eg, a woman who is not heterosexually active becomes active) a
female participant or female partner of a male participant must begin a highly effective
method of contraception, as described throughout the inclusion criteria. If reproductive
status is questionable, additional evaluation should be considered.
13. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the
purposes of assisted reproduction during the study and for a period of at least 1 month
after receiving the last dose of study drug.
14. During the study and for a minimum of 1 spermatogenesis cycle (defined as
approximately 3 months) after receiving the last dose of study drug, a man
who is sexually active with a woman of childbearing potential must agree to use
a barrier method of contraception (eg, condom with spermicidal
foam/gel/film/cream/suppository) and his female partner must use a highly
effective method of contraception.
who is sexually active with a woman who is pregnant must use a condom.
must agree not to donate sperm.
15. Must be willing and able to adhere to the prohibitions specified in this protocol.
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. Male or female, aged 18 to 74 years (inclusive).
Note: Participants should be at least 18 years of age or older as per the legal age of consent
in the jurisdiction in which the study is taking place.
2. Meet DSM-5 diagnostic criteria for MDD, without psychotic features (DSM-5 296.22,
296.23, 296.32, or 296.33), based upon clinical assessment and confirmed by the
SCID-CT diagnosed with first depressive episode prior to age 60. The length of the
current depressive episode must be ≤18 months.
3. Have had an inadequate response to at least 1 but no more than 2 antidepressants (see the
inclusion criterion 4 below), administered at an adequate dose and duration in the current
episode of depression. The current antidepressant cannot be the first antidepressant
treatment for the first lifetime episode of depression. An inadequate response is defined
as <50% reduction but with some improvement in depressive symptom severity with
residual symptoms present other than insomnia, and overall good tolerability, as assessed
by the MGH-ATRQ. An adequate trial is defined as an antidepressant treatment for at
least 6 weeks (and no greater than 12 months in the current episode) at or above the stable
therapeutic dose specified in the MGH-ATRQ, must include the participant’s current
antidepressant treatment. Note: Participants with no improvement on the current
SSRI/SNRI should not be enrolled in the study. If the participant has received
2 SSRI/SNRI treatments of sufficient dose and duration in the current episode, and has
shown <25% improvement to both, then the participant would not qualify based on
exclusion criterion 9.
4. Is receiving and tolerating well any one of the following SSRI or SNRI for depressive
symptoms, in any formulation and available in the participating country: citalopram,
duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran,
paroxetine, sertraline, venlafaxine, desvenlafaxine, vilazodone, or vortioxetine at a stable
dose (at therapeutic dose level) for at least 6 weeks, and for no greater than 12 months in
the current episode, at screening.
Note: Dose and duration of treatment should be documented in the source documents by
the investigator based on available evidence such as using the medical or pharmacy
records. The investigator will use this information to complete the MGH-ATRQ.
Note: Participants using fluvoxamine as baseline SSRI and have normal renal and hepatic
function may enter the study. See renal and hepatic function restrictions in Section 6.5
(Concomitant Therapy).
5. Have a HDRS-17 total score ≥22 at screening and must not demonstrate a clinically
significant improvement (ie, an improvement of >20% on their HDRS-17 total score)
from the beginning to end of screening (from the first to the second independent HDRS17 rating), so long as the HDRS-17 total score is ≥18 at the end of screening (Day -5 to -
2 visit).
6. Body mass index (BMI) between 18 and 37 kg/m2
inclusive (BMI=weight/height2).
7. Must be an outpatient at screening.
8. Participant must be medically stable on the basis of the following performed at screening:
physical examination, vital signs (including blood pressure), and 12-lead ECG performed
at screening and baseline. If there are any abnormalities that are not specified in the
inclusion and exclusion criteria, their clinical significance must be determined by the
investigator and recorded in the participant's source documents and initialed by the
investigator.
9. Participant must be medically stable on the basis of clinical laboratory tests performed at
screening. If the results of the serum chemistry panel, hematology, or urinalysis are
outside the normal reference ranges, the participant may be included only if the
investigator judges the abnormalities or deviations from normal to be not clinically
significant or to be appropriate and reasonable for the population under study. This
determination must be recorded in the participant's source documents and initialed by the
investigator.
10. Must sign an ICF indicating that he or she understands the purpose of and procedures
required for the study and be willing to participate in the study.
11. A woman of childbearing potential must have a negative highly sensitive serum (β human
chorionic gonadotropin [β-hCG]) pregnancy test at screening and a negative urine
pregnancy test predose on Day 1 of the DB phase prior to randomization.
12. Contraceptive use by men or women should be consistent with local regulations regarding
the use of contraceptive methods for participants in clinical studies.
a. Before entering the study, a woman must be either:
Postmenopausal
A postmenopausal state is defined as no menses for 12 months without an
alternative medical cause. A high follicle stimulating hormone (FSH) level in the
postmenopausal range based on the reference range of the central laboratory
may be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy, however in the absence of
12 months of amenorrhea, a single FSH measurement is insufficient.
Permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy,
bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
b. Of childbearing potential and
Practicing a highly effective method of contraception (failure rate of <1% per year
when used consistently and correctly) (see Section 10.5, Appendix 5,
Contraceptive and Barrier Guidance and Collection of Pregnancy Information).
The investigator should evaluate the potential for contraceptive method failure
(eg, noncompliance, recently initiated) in relationship to the first dose of study
intervention.
Examples of highly effective contraceptives include:
− User independent methods:
implantable progestogen-only hormone contraception associated with
inhibition of ovulation; intrauterine device (IUD); intrauterine hormonereleasing system (IUS); vasectomized partner; sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining
from heterosexual intercourse during the entire period of risk associated with
the study drug. The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the study and the preferred and usual lifestyle of the
participant.)
− User-dependent methods:
combined (estrogen- and progestogen-containing) hormonal contraception
associated with inhibition of ovulation: oral, intravaginal, and transdermal;
progestogen-only hormone contraception associated with inhibition of
ovulation: oral and injectable
Typical use failure rates may differ from those when used consistently and
correctly. Use should be consistent with local regulations regarding the use of
contraceptive methods for participants in clinical studies
Agrees to remain on a highly effective method throughout the study and for at
least 1 month after the last dose of study drug.
Note: If the childbearing potential status changes after start of the study or the risk of
pregnancy changes (eg, a woman who is not heterosexually active becomes active) a
female participant or female partner of a male participant must begin a highly effective
method of contraception, as described throughout the inclusion criteria. If reproductive
status is questionable, additional evaluation should be considered.
13. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the
purposes of assisted reproduction during the study and for a period of at least 1 month
after receiving the last dose of study drug.
14. During the study and for a minimum of 1 spermatogenesis cycle (defined as
approximately 3 months) after receiving the last dose of study drug, a man
who is sexually active with a woman of childbearing potential must agree to use
a barrier method of contraception (eg, condom with spermicidal
foam/gel/film/cream/suppository) and his female partner must use a highly
effective method of contraception.
who is sexually active with a woman who is pregnant must use a condom.
must agree not to donate sperm.
15. Must be willing and able to adhere to the prohibitions specified in this protocol.
Exclusion Criteria
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. Has a recent (last 3 months) history of, or current signs and symptoms of,
− severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min);
− clinically significant or unstable cardiovascular, respiratory, gastrointestinal,
neurologic, hematologic, rheumatologic, immunologic or endocrine disorders.
− uncontrolled Type 1 or Type 2 diabetes mellitus. Note: Participants with Type 1
or Type 2 diabetes mellitus who are controlled (hemoglobin A1C ≤8.0% and
glucose ≤136 mg/dL at screening) may be eligible to participate if otherwise
medically healthy, and if on a stable regimen of glucose-lowering medications
for at least 2 months prior to screening.
2. Has a history of narcolepsy or seizures (except childhood seizures)
3. Has clinically significant hepatic disease as defined by:
− ≥2x Upper Limit of Normal (ULN) increase of aspartate aminotransferase (AST)
or alanine aminotransferase (ALT) at screening (one retest is permitted)
− significant liver disease including cirrhosis, ascites, active hepatitis etc (fatty
liver disease and Gilbert’s syndrome will be allowed as long as it does not meet
above criteria).
4. Has taken a strong inhibitor of CYP3A4 or CYP2C9 or moderate/strong inducer of
CYP3A4 or CYP2C9 or a dual inhibitor/inducer of CYP3A4 and CYP2C9 within 14 days
before the first study drug administration on Day 1 or will require treatment during the
study. See Section 10.6, Appendix 6, for examples of strong inhibitors and
moderate/strong inducers of CYP3A4 or CYP2C9 or dual inhibitors/inducers of CYP3A4
and CYP2C9.
5. Has taken a moderate inhibitor of CYP3A4 or CYP2C9 within 14 days before the first
study drug administration on Day 1 or will require treatment during the study and has:
− limited renal (CrCl <60 mL/min) or
− hepatic disease (AST/ALT >1.5X ULN and bilirubin >1.5X ULN).
See Section 10.6, Appendix 6, for examples of moderate CYP3A4 or CYP2C9 inhibitors.
6. Has current signs/symptoms of hypothyroidism or hyperthyroidism. For participants with
a history of thyroid disease and for participants who, regardless of thyroid history have
the thyroid stimulating hormone (TSH) value out of range, a free thyroxine (FT4) test will
be conducted. If the FT4 value is abnormal and considered to be clinically significant
(after discussion with the sponsor’s study responsible physician/scientist or designee) the
participant is not eligible.
Participants with a pre-existing history of thyroid disease/disorder who are treated with
thyroid hormones need to be on a stable dosage for 3 months prior to the start of the
screening phase.
Participants taking thyroid supplementation for antidepressant purposes are not allowed
in the study.
7. Has Cushing’s Disease, Addison’s Disease, primary amenorrhea, or other evidence of
significant medical disorders of the HPA axis.
8. Has a current or recent history of homicidal ideation or serious suicidal ideation within
the past 3 months, corresponding to a positive response on item 4 (active suicidal ideation
with some intent to act, without specific plan) or item 5 (active suicidal ideation with
specific plan and intent) for ideation on the C-SSRS, or a history of suicidal behavior
within the past year, as validated by the C-SSRS at screening or Day 1. Participants with
a prior suicide attempt of any sort, or prior serious suicidal ideation/plan within the past
6 months, should be carefully screened for current suicidal ideation and only participants
with non-serious items (1-3 of the suicidal ideation section of the C-SSRS) may be
included at the discretion of the investigator.
9. Has a history of treatment-resistant MDD, defined as a lack of response to 2 or more
adequate antidepressant treatments in the current episode, as indicated by no or minimal
(<25% improvement in symptoms) when treated with an antidepressant of adequate dose
(per MGH-ATRQ) and duration (at least 6 weeks).
10. Has a history or evidence of clinically meaningful noncompliance with current
antidepressant therapy.
11. Has a primary DSM-5 diagnosis of panic disorder, generalized anxiety disorder, social
anxiety disorder, or specific phobia which has been the primary focus of psychiatric
treatment within the past 2 years. These are allowed as secondary diagnoses if MDD is
the primary focus of treatment according to the investigator.
12. Current active DSM-5 diagnosis of obsessive-compulsive disorder, posttraumatic stress
disorder, anorexia nervosa, or bulimia nervosa. These disorders need to be in remission
for at least 1 year for the participant to be enrolled.
13. Has history or current diagnosis of a psychotic disorder, bipolar disorder, intellectual
disability, autism spectrum disorder, borderline personality disorder, somatoform
disorders, or fibromyalgia.
14. Has any significant primary sleep disorder, including but not limited to obstructive sleep
apnea, restless leg syndrome, or parasomnias. Patients with insomnia disorder are
allowed.
15. Has a history of moderate to severe substance use disorder including alcohol use disorder
according to DSM-5 criteria within 6 months before screening or positive test result(s)
for alcohol and/or drugs of abuse (eg, opiates [including methadone], cocaine,
amphetamines, methamphetamines, cannabinoids, cannabidiol [CBD], barbiturates,
3,4-Methylenedioxymethamphetamine [MDMA]) at screening or at baseline.
Note: Tobacco and caffeine use are not exclusionary.
16. Taking at screening benzodiazepines at high dosages greater than the equivalent of 30 mg
diazepam or 3 mg of lorazepam at long duration which might result in benzodiazepine
withdrawal syndrome. Participants must have a negative benzodiazepine test at baseline
and be free of signs of the benzodiazepine abstinence syndrome. (see Section 10.8,
Appendix 8: Benzodiazepine Equivalence Table).
17. Had a clinically significant acute illness, per investigator judgment, within 7 days
before the first dose of study drug.
18. Has a known malignancy or history of malignancy within 5 years before screening
(exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of
the cervix, or malignancy that in the opinion of the investigator, with concurrence with
the sponsor's study responsible physician/scientist or designee, is considered cured with
minimal risk of recurrence).
19. Has clinically significant ECG abnormalities at screening or Day 1 prior to
randomization that may jeopardize the participants’ safety or the integrity of the study,
in the Investigator’s judgment, defined as:
− During screening and/or Day 1, a QT interval corrected according to
Fridericia’s formula (QTcF): ≥450 msec (males); ≥470 msec (females)
− Evidence of 2nd and 3rd degree atrioventricular block.
− Features of new ischemia
− Other clinically important arrhythmia or cardiac abnormalities
20. Has within the last 5 years received any prior antidepressant treatment with
ketamine/esketamine, electroconvulsive therapy, vagal nerve stimulation, or a deep brain
stimulation device.
21. Ongoing psychological treatments (eg, Cognitive Behavior Therapy, Interpersonal
Psychotherapy, Psychodynamic Psychotherapy etc.), initiated within 6 weeks prior to
start of screening. Note: a participant who has been receiving ongoing psychological
treatment for a period of greater than 6 weeks is eligible, if the investigator deems the
psychological treatment to be of stable duration and frequency.
22. Has received experimental therapies (psychological, pharmacologic or noninvasive
device) within 30 days before screening or if greater than 2 experimental therapies in the
past year prior to screening.
23. Has known allergies, hypersensitivity, intolerance or any contraindication to seltorexant
or its excipients (refer to Investigator's Brochure19).
24. Has had a >7 days exposure or poor tolerability to seltorexant in previous studies (per
patient report or other information).
25. Donation of 1 or more units (approximately 450 mL) of blood or acute loss of an
equivalent amount of blood within 30 days before the first dose of study drug.
26. Has cognitive impairment per investigator judgment that would render the informed
consent invalid or limit the ability of the participant to comply with the study
requirements. Participant has neurodegenerative disorder (eg, Alzheimer’s disease,
vascular dementia, Parkinson’s disease with clinical evidence of cognitive impairment)
or evidence of mild cognitive impairment (MCI). Participants of age ≥65 years: has a
MMSE <25 or <23 for those participants with less than high school equivalent education.
27. Has any condition for which, in the opinion of the investigator, participation would not
be in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
28. Has taken any disallowed therapies as noted in Section 6.5, Concomitant Therapy.
29. Is pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study
or within 1 month after the last dose of study drug.
30. Plans to father a child while enrolled in this study or within 3 months after the last dose
of study drug.
31. Has had major surgery, (eg, requiring general anesthesia) within 2 weeks before
screening, or will not have fully recovered from surgery, or has surgery planned during
the time the participant is expected to participate in the study.
Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate.
32. Employee of the investigator or study site, with direct involvement in the proposed study
or other studies under the direction of that investigator or study site, as well as family
members of the employees or the investigator.
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. Has a recent (last 3 months) history of, or current signs and symptoms of,
− severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min);
− clinically significant or unstable cardiovascular, respiratory, gastrointestinal,
neurologic, hematologic, rheumatologic, immunologic or endocrine disorders.
− uncontrolled Type 1 or Type 2 diabetes mellitus. Note: Participants with Type 1
or Type 2 diabetes mellitus who are controlled (hemoglobin A1C ≤8.0% and
glucose ≤136 mg/dL at screening) may be eligible to participate if otherwise
medically healthy, and if on a stable regimen of glucose-lowering medications
for at least 2 months prior to screening.
2. Has a history of narcolepsy or seizures (except childhood seizures)
3. Has clinically significant hepatic disease as defined by:
− ≥2x Upper Limit of Normal (ULN) increase of aspartate aminotransferase (AST)
or alanine aminotransferase (ALT) at screening (one retest is permitted)
− significant liver disease including cirrhosis, ascites, active hepatitis etc (fatty
liver disease and Gilbert’s syndrome will be allowed as long as it does not meet
above criteria).
4. Has taken a strong inhibitor of CYP3A4 or CYP2C9 or moderate/strong inducer of
CYP3A4 or CYP2C9 or a dual inhibitor/inducer of CYP3A4 and CYP2C9 within 14 days
before the first study drug administration on Day 1 or will require treatment during the
study. See Section 10.6, Appendix 6, for examples of strong inhibitors and
moderate/strong inducers of CYP3A4 or CYP2C9 or dual inhibitors/inducers of CYP3A4
and CYP2C9.
5. Has taken a moderate inhibitor of CYP3A4 or CYP2C9 within 14 days before the first
study drug administration on Day 1 or will require treatment during the study and has:
− limited renal (CrCl <60 mL/min) or
− hepatic disease (AST/ALT >1.5X ULN and bilirubin >1.5X ULN).
See Section 10.6, Appendix 6, for examples of moderate CYP3A4 or CYP2C9 inhibitors.
6. Has current signs/symptoms of hypothyroidism or hyperthyroidism. For participants with
a history of thyroid disease and for participants who, regardless of thyroid history have
the thyroid stimulating hormone (TSH) value out of range, a free thyroxine (FT4) test will
be conducted. If the FT4 value is abnormal and considered to be clinically significant
(after discussion with the sponsor’s study responsible physician/scientist or designee) the
participant is not eligible.
Participants with a pre-existing history of thyroid disease/disorder who are treated with
thyroid hormones need to be on a stable dosage for 3 months prior to the start of the
screening phase.
Participants taking thyroid supplementation for antidepressant purposes are not allowed
in the study.
7. Has Cushing’s Disease, Addison’s Disease, primary amenorrhea, or other evidence of
significant medical disorders of the HPA axis.
8. Has a current or recent history of homicidal ideation or serious suicidal ideation within
the past 3 months, corresponding to a positive response on item 4 (active suicidal ideation
with some intent to act, without specific plan) or item 5 (active suicidal ideation with
specific plan and intent) for ideation on the C-SSRS, or a history of suicidal behavior
within the past year, as validated by the C-SSRS at screening or Day 1. Participants with
a prior suicide attempt of any sort, or prior serious suicidal ideation/plan within the past
6 months, should be carefully screened for current suicidal ideation and only participants
with non-serious items (1-3 of the suicidal ideation section of the C-SSRS) may be
included at the discretion of the investigator.
9. Has a history of treatment-resistant MDD, defined as a lack of response to 2 or more
adequate antidepressant treatments in the current episode, as indicated by no or minimal
(<25% improvement in symptoms) when treated with an antidepressant of adequate dose
(per MGH-ATRQ) and duration (at least 6 weeks).
10. Has a history or evidence of clinically meaningful noncompliance with current
antidepressant therapy.
11. Has a primary DSM-5 diagnosis of panic disorder, generalized anxiety disorder, social
anxiety disorder, or specific phobia which has been the primary focus of psychiatric
treatment within the past 2 years. These are allowed as secondary diagnoses if MDD is
the primary focus of treatment according to the investigator.
12. Current active DSM-5 diagnosis of obsessive-compulsive disorder, posttraumatic stress
disorder, anorexia nervosa, or bulimia nervosa. These disorders need to be in remission
for at least 1 year for the participant to be enrolled.
13. Has history or current diagnosis of a psychotic disorder, bipolar disorder, intellectual
disability, autism spectrum disorder, borderline personality disorder, somatoform
disorders, or fibromyalgia.
14. Has any significant primary sleep disorder, including but not limited to obstructive sleep
apnea, restless leg syndrome, or parasomnias. Patients with insomnia disorder are
allowed.
15. Has a history of moderate to severe substance use disorder including alcohol use disorder
according to DSM-5 criteria within 6 months before screening or positive test result(s)
for alcohol and/or drugs of abuse (eg, opiates [including methadone], cocaine,
amphetamines, methamphetamines, cannabinoids, cannabidiol [CBD], barbiturates,
3,4-Methylenedioxymethamphetamine [MDMA]) at screening or at baseline.
Note: Tobacco and caffeine use are not exclusionary.
16. Taking at screening benzodiazepines at high dosages greater than the equivalent of 30 mg
diazepam or 3 mg of lorazepam at long duration which might result in benzodiazepine
withdrawal syndrome. Participants must have a negative benzodiazepine test at baseline
and be free of signs of the benzodiazepine abstinence syndrome. (see Section 10.8,
Appendix 8: Benzodiazepine Equivalence Table).
17. Had a clinically significant acute illness, per investigator judgment, within 7 days
before the first dose of study drug.
18. Has a known malignancy or history of malignancy within 5 years before screening
(exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of
the cervix, or malignancy that in the opinion of the investigator, with concurrence with
the sponsor's study responsible physician/scientist or designee, is considered cured with
minimal risk of recurrence).
19. Has clinically significant ECG abnormalities at screening or Day 1 prior to
randomization that may jeopardize the participants’ safety or the integrity of the study,
in the Investigator’s judgment, defined as:
− During screening and/or Day 1, a QT interval corrected according to
Fridericia’s formula (QTcF): ≥450 msec (males); ≥470 msec (females)
− Evidence of 2nd and 3rd degree atrioventricular block.
− Features of new ischemia
− Other clinically important arrhythmia or cardiac abnormalities
20. Has within the last 5 years received any prior antidepressant treatment with
ketamine/esketamine, electroconvulsive therapy, vagal nerve stimulation, or a deep brain
stimulation device.
21. Ongoing psychological treatments (eg, Cognitive Behavior Therapy, Interpersonal
Psychotherapy, Psychodynamic Psychotherapy etc.), initiated within 6 weeks prior to
start of screening. Note: a participant who has been receiving ongoing psychological
treatment for a period of greater than 6 weeks is eligible, if the investigator deems the
psychological treatment to be of stable duration and frequency.
22. Has received experimental therapies (psychological, pharmacologic or noninvasive
device) within 30 days before screening or if greater than 2 experimental therapies in the
past year prior to screening.
23. Has known allergies, hypersensitivity, intolerance or any contraindication to seltorexant
or its excipients (refer to Investigator's Brochure19).
24. Has had a >7 days exposure or poor tolerability to seltorexant in previous studies (per
patient report or other information).
25. Donation of 1 or more units (approximately 450 mL) of blood or acute loss of an
equivalent amount of blood within 30 days before the first dose of study drug.
26. Has cognitive impairment per investigator judgment that would render the informed
consent invalid or limit the ability of the participant to comply with the study
requirements. Participant has neurodegenerative disorder (eg, Alzheimer’s disease,
vascular dementia, Parkinson’s disease with clinical evidence of cognitive impairment)
or evidence of mild cognitive impairment (MCI). Participants of age ≥65 years: has a
MMSE <25 or <23 for those participants with less than high school equivalent education.
27. Has any condition for which, in the opinion of the investigator, participation would not
be in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
28. Has taken any disallowed therapies as noted in Section 6.5, Concomitant Therapy.
29. Is pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study
or within 1 month after the last dose of study drug.
30. Plans to father a child while enrolled in this study or within 3 months after the last dose
of study drug.
31. Has had major surgery, (eg, requiring general anesthesia) within 2 weeks before
screening, or will not have fully recovered from surgery, or has surgery planned during
the time the participant is expected to participate in the study.
Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate.
32. Employee of the investigator or study site, with direct involvement in the proposed study
or other studies under the direction of that investigator or study site, as well as family
members of the employees or the investigator.
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
550 participants
