We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04513912




Registration number
NCT04513912
Ethics application status
Date submitted
13/08/2020
Date registered
14/08/2020
Date last updated
3/05/2021

Titles & IDs
Public title
A Study of Seltorexant Compared to Quetiapine XR as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy
Scientific title
Double-Blind, Randomized, Parallel-Group Study With Quetiapine Extended Release as Comparator 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
Secondary ID [1] 0 0
42847922MDD3005
Secondary ID [2] 0 0
CR108810
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depressive Disorder, Major 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Seltorexant
Treatment: Drugs - Matching placebo to Seltorexant
Treatment: Drugs - Quetiapine XR
Treatment: Drugs - Matching placebo to Quetiapine XR

Experimental: Seltorexant - Adult participants will receive seltorexant once daily from Day 1-7 and together with matching placebo from Day 8 till Day 182. Elderly participants will receive seltorexant once daily from Day 1-3 and together with matching placebo from Day 4 till Day 182.

Active Comparator: Quetiapine Extended-Release (XR) - Adult participants will receive quetiapine XR once daily from Day 1-2, followed by an increase in dose from Day 3-7, and from Day 8-14 together with matching placebo. After Day 14, quetiapine XR twice daily from Day 14 till Day 182. Elderly participants will receive quetiapine XR once daily from Day 1-3 and twice from Day 4-7, followed by an increase in dose once daily from Day 8-14 together with matching placebo. After Day 14 till Day 182, quetiapine XR will be adjusted by investigator based on the participant's clinical response and tolerability.


Treatment: Drugs: Seltorexant
Participants will receive seltorexant over-encapsulated tablet orally.

Treatment: Drugs: Matching placebo to Seltorexant
Participants will receive placebo over-encapsulated tablet matching to seltorexant orally.

Treatment: Drugs: Quetiapine XR
Participants will receive quetiapine XR capsule orally.

Treatment: Drugs: Matching placebo to Quetiapine XR
Participants will receive placebo capsule matching to quetiapine XR orally.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Response (>=50 Percent improvement in MADRS total score from baseline) at Week 26 - Responders are defined as percentage of participants with greater than or equal to (>=) 50 percent (%) improvement in the montgomery-asberg depression rating scale (MADRS) total score from baseline. 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.
Timepoint [1] 0 0
Week 26
Secondary outcome [1] 0 0
Change from baseline in Weight up to Week 26 - Change from baseline in weight will be reported.
Timepoint [1] 0 0
Baseline to Week 26
Secondary outcome [2] 0 0
Time to Study Drug Discontinuation for Potentially Treatment Related Reasons - Time to discontinuation of study drug for potentially treatment related reasons will be reported. Potentially treatment related reasons are defined as all study drug discontinuations excluding the potentially non-treatment related discontinuations (eg, loss of insurance for antidepressant therapy, movement/travel out of the area, change of work-schedule being unable to accommodate visit schedule, family circumstances).
Timepoint [2] 0 0
Up to Week 26
Secondary outcome [3] 0 0
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score - 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.
Timepoint [3] 0 0
Baseline to Week 26
Secondary outcome [4] 0 0
Change from Baseline in MADRS-6 Total Score - The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).
Timepoint [4] 0 0
Baseline to Week 26
Secondary outcome [5] 0 0
Change from Baseline in the MADRS Without Sleep Item (MADRS-WOSI) Total Score - The MADRS is a 10-item clinician-rated instrument for evaluating severity of symptoms of depression. Each item is rated on a scale from 0 to 6, with higher scores indicating greater symptom severity. MADRS-WOSI considered 9 of the 10 MADRS items, excluding "reduced sleep" item. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity.
Timepoint [5] 0 0
Baseline to Week 26
Secondary outcome [6] 0 0
Change from Baseline in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score - The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the diagnostic and statistical manual of mental disorders-5th edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.
Timepoint [6] 0 0
Baseline to Week 26
Secondary outcome [7] 0 0
Percentage of Participants with Remission (MADRS Total Score less than or equal to (<=) 12) at Week 26 - Percentage of participants with remission (MADRS total Score <=12) will be reported.
Timepoint [7] 0 0
Week 26
Secondary outcome [8] 0 0
Percentage of Participants with a >=50 Percent Improvement in MADRS Total Score and MADRS <=18 at Week 26 - Percentage of participants with a >=50 percent improvement in MADRS total score and MADRS <=18 at Week 26.
Timepoint [8] 0 0
Week 26
Secondary outcome [9] 0 0
Percentage of Participants with Weight Increase >=7 Percent from Baseline at Week 26 - Percentage of participants with weight increase >=7 percent from baseline will be reported.
Timepoint [9] 0 0
Week 26

Eligibility
Key inclusion criteria
- Meet diagnostic and statistical manual of mental disorders-5th edition (DSM-5)
diagnostic criteria for major depressive disorder (MDD), without psychotic features,
based upon clinical assessment and confirmed by the structured clinical interview for
DSM-5 Axis I disorders-clinical trials version (SCID-CT) diagnosed with first
depressive episode prior to age 60. The length of the current depressive episode must
be less than or equal to (<=) 18 months

- Have had an inadequate response to at least 1 but no more than 2 antidepressants,
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 less than (<) 50
percent (%) reduction but with some improvement in depressive symptom severity with
residual symptoms beyond insomnia present, and overall good tolerability, as assessed
by the Massachusetts General Hospital-Antidepressant Treatment Response Questionnaire
(MGH-ATRQ)

- Is receiving and tolerating well any one of the following selective serotonin reuptake
inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (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 or above therapeutic dose level) for at least 6 weeks, and for no
greater than 12 months in the current episode, at screening

- Have a hamilton depression rating scale (HDRS)-17 total score greater than or equal to
(>=) 22 at the first screening visit and must not demonstrate a clinically significant
improvement (that is, an improvement of greater than [>] 20 percent [%] on their
HDRS-17 total score) from the beginning to end of screening

- Have a patient version insomnia severity index (ISI) total score >= 15 as well as a
clinician version of the ISI total score >= 15 at the second screening visit

- Body mass index (BMI) between 18 and 37 kilogram per meter square (kg/m^2) inclusive
(BMI=weight/height^2)

- Participant must be medically stable on the basis of the following: physical
examination, vital signs (including blood pressure), and 12-lead electrocardiogram
(ECG) performed at screening and baseline
Minimum age
18 Years
Maximum age
74 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has a recent (last 3 months) history of, or current signs and symptoms of, severe
renal insufficiency (creatinine clearance [CrCl] less than [<] 30 milliliter per
minute [mL/min]); clinically significant or unstable cardiovascular, respiratory,
gastrointestinal, neurologic, hematologic, rheumatologic, immunologic or endocrine
disorders. uncontrolled Type 1 or Type 2 diabetes mellitus

- 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)

- Has history or current diagnosis of a psychotic disorder, bipolar disorder,
intellectual disability, autism spectrum disorder, borderline personality disorder,
somatoform disorders

- Has a history of moderate to severe substance use disorder including alcohol use
disorder according to DSM-5 criteria within 6 months before screening

- Has any significant primary sleep disorder, including but not limited to obstructive
sleep apnea, restless leg syndrome, or parasomnias. Participants with insomnia
disorder are allowed

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Albert Road Clinic - Melbourne
Recruitment hospital [2] 0 0
Neuro Trials Victoria - Noble Park
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3174 - Noble Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
United States of America
State/province [24] 0 0
Wisconsin
Country [25] 0 0
Argentina
State/province [25] 0 0
Ciudad Autonoma Buenos Aires
Country [26] 0 0
Argentina
State/province [26] 0 0
Ciudad Autonoma de Buenos Aires
Country [27] 0 0
Argentina
State/province [27] 0 0
Cordoba
Country [28] 0 0
Argentina
State/province [28] 0 0
La Plata
Country [29] 0 0
Argentina
State/province [29] 0 0
San Miguel de Tucuman
Country [30] 0 0
Austria
State/province [30] 0 0
Innsbruck
Country [31] 0 0
Belgium
State/province [31] 0 0
Brugge
Country [32] 0 0
Belgium
State/province [32] 0 0
Sint-Niklaas
Country [33] 0 0
Belgium
State/province [33] 0 0
Yvoir
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Plovdiv
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Ruse
Country [36] 0 0
Bulgaria
State/province [36] 0 0
Sofia
Country [37] 0 0
Bulgaria
State/province [37] 0 0
Stara Zagora
Country [38] 0 0
Bulgaria
State/province [38] 0 0
Tzarev Brod
Country [39] 0 0
Bulgaria
State/province [39] 0 0
Varna
Country [40] 0 0
Bulgaria
State/province [40] 0 0
Veliko Tarnovo
Country [41] 0 0
Canada
State/province [41] 0 0
Nova Scotia
Country [42] 0 0
Canada
State/province [42] 0 0
Ontario
Country [43] 0 0
Canada
State/province [43] 0 0
Quebec
Country [44] 0 0
Czechia
State/province [44] 0 0
Brno
Country [45] 0 0
Czechia
State/province [45] 0 0
Hradec Kralove
Country [46] 0 0
Czechia
State/province [46] 0 0
Praha 10
Country [47] 0 0
Czechia
State/province [47] 0 0
Praha 6
Country [48] 0 0
Czechia
State/province [48] 0 0
Praha 8
Country [49] 0 0
Estonia
State/province [49] 0 0
Tallinn
Country [50] 0 0
Estonia
State/province [50] 0 0
Tartu
Country [51] 0 0
Latvia
State/province [51] 0 0
Jelgava
Country [52] 0 0
Latvia
State/province [52] 0 0
Liepaja
Country [53] 0 0
Latvia
State/province [53] 0 0
Outpatient Centre Of Psychiatry
Country [54] 0 0
Latvia
State/province [54] 0 0
Riga
Country [55] 0 0
Lithuania
State/province [55] 0 0
Kaunas
Country [56] 0 0
Lithuania
State/province [56] 0 0
Silute
Country [57] 0 0
Lithuania
State/province [57] 0 0
Vilnius
Country [58] 0 0
Malaysia
State/province [58] 0 0
Ipoh
Country [59] 0 0
Malaysia
State/province [59] 0 0
Johor Bahru
Country [60] 0 0
Malaysia
State/province [60] 0 0
Seremban
Country [61] 0 0
Poland
State/province [61] 0 0
Bialystok
Country [62] 0 0
Poland
State/province [62] 0 0
Bydgoszcz
Country [63] 0 0
Poland
State/province [63] 0 0
Gdansk
Country [64] 0 0
Poland
State/province [64] 0 0
Katowice
Country [65] 0 0
Poland
State/province [65] 0 0
Lodz
Country [66] 0 0
Poland
State/province [66] 0 0
Poznan
Country [67] 0 0
Poland
State/province [67] 0 0
Warszawa
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Ekaterinburg
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Engels, Saratov Region
Country [70] 0 0
Russian Federation
State/province [70] 0 0
Kemerovo
Country [71] 0 0
Russian Federation
State/province [71] 0 0
Lipetsk Region
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Moscow
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Omsk
Country [74] 0 0
Russian Federation
State/province [74] 0 0
St. Petersburg
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Tomsk
Country [76] 0 0
Serbia
State/province [76] 0 0
Belgrade
Country [77] 0 0
Serbia
State/province [77] 0 0
Kovin
Country [78] 0 0
Serbia
State/province [78] 0 0
Kragujevac
Country [79] 0 0
Serbia
State/province [79] 0 0
Nis
Country [80] 0 0
Serbia
State/province [80] 0 0
Novi Knezevac
Country [81] 0 0
Slovakia
State/province [81] 0 0
Banska Bystrica
Country [82] 0 0
Slovakia
State/province [82] 0 0
Bojnice
Country [83] 0 0
Slovakia
State/province [83] 0 0
Liptovsky Mikulas
Country [84] 0 0
Slovakia
State/province [84] 0 0
Rimavska Sobota
Country [85] 0 0
Slovakia
State/province [85] 0 0
Trencin
Country [86] 0 0
Slovakia
State/province [86] 0 0
Trnava
Country [87] 0 0
Slovakia
State/province [87] 0 0
Zilina
Country [88] 0 0
Ukraine
State/province [88] 0 0
Glevakha
Country [89] 0 0
Ukraine
State/province [89] 0 0
Kharkiv
Country [90] 0 0
Ukraine
State/province [90] 0 0
Kyiv
Country [91] 0 0
Ukraine
State/province [91] 0 0
Ternopil
Country [92] 0 0
Ukraine
State/province [92] 0 0
Uzhgorod
Country [93] 0 0
Ukraine
State/province [93] 0 0
Zaporizhzhia
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Derby
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Greater Manchester
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Harrogate
Country [97] 0 0
United Kingdom
State/province [97] 0 0
London
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Redruth
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Sunderland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the efficacy of seltorexant compared with quetiapine
extended-release (XR) as adjunctive therapy to an antidepressant drug in treatment response
in participants with major depressive disorder with insomnia symptoms (MDDIS) who have had an
inadequate response to current antidepressant therapy with a selective serotonin reuptake
inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
Trial website
https://clinicaltrials.gov/show/NCT04513912
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04513912