Clinical Trial Results:
Randomized, Double-blind, Multicenter, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants with Major Depressive Disorder (MDD) with Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy
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Summary
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EudraCT number |
2022-000439-22 |
Trial protocol |
SE CZ ES HU BE BG PT PL |
Global end of trial date |
18 Sep 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Oct 2025
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First version publication date |
23 Oct 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
67953964MDD3001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05455684 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Janssen-Cilag International N.V.
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Sponsor organisation address |
Turnhoutseweg 30, Beerse, Belgium, B-2340
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Public contact |
Clinical Registry Group, Janssen-Cilag International N.V., ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Janssen-Cilag International N.V., ClinicalTrialsEU@its.jnj.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Sep 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Sep 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the study was to evaluate the efficacy of aticaprant 10 mg compared with placebo as adjunctive therapy to an antidepressant in improving depressive symptoms in adult participants with major depressive disorder (MDD) with moderate-to-severe anhedonia (ANH+) who have had an inadequate response to current antidepressant therapy with an selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitors (SNRI).
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Jun 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 34
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Country: Number of subjects enrolled |
Australia: 13
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Country: Number of subjects enrolled |
Belgium: 24
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Country: Number of subjects enrolled |
Brazil: 41
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Country: Number of subjects enrolled |
Bulgaria: 33
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Country: Number of subjects enrolled |
Czechia: 38
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Country: Number of subjects enrolled |
Hungary: 6
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Country: Number of subjects enrolled |
Italy: 3
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Country: Number of subjects enrolled |
Poland: 31
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Country: Number of subjects enrolled |
Portugal: 5
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Country: Number of subjects enrolled |
Spain: 16
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Country: Number of subjects enrolled |
Sweden: 37
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Country: Number of subjects enrolled |
United States: 230
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Worldwide total number of subjects |
511
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EEA total number of subjects |
193
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
425
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From 65 to 84 years |
86
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 513 participants were enrolled in the study, of whom 511 received the treatment and were included in the analysis. | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Adult participants aged 18 to 64 years who had major depressive disorder (MDD) with or without moderate-to-severe anhedonia (ANH+ or ANH-) and elderly participants aged 65 to 74 years with MDD (ANH+ and ANH-) who had an inadequate response to an ongoing antidepressant therapy were randomized in the study. | |||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||||||||||||||||||||
Arm description |
During DB treatment phase, participants received placebo matching to aticaprant tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (selective serotonin reuptake inhibitor/serotonin–norepinephrine reuptake inhibitor [SSRI/SNRI]). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003. | |||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received placebo matching to aticaprant tablet orally once daily from Day 1 to Day 42.
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Arm title
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Aticaprant 10 mg | |||||||||||||||||||||||||||||||||
Arm description |
During DB treatment phase, participants received aticaprant 10 milligrams (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Aticaprant 10 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received aticaprant 10 mg tablet orally once daily from Day 1 to Day 42.
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Only reported subjects were planned to be included in this milestone. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Only reported subjects were planned to be included in this milestone. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
During DB treatment phase, participants received placebo matching to aticaprant tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (selective serotonin reuptake inhibitor/serotonin–norepinephrine reuptake inhibitor [SSRI/SNRI]). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Aticaprant 10 mg
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Reporting group description |
During DB treatment phase, participants received aticaprant 10 milligrams (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
DB: Placebo
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
During DB treatment phase, participants received placebo matching to aticaprant tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI).
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Subject analysis set title |
DB: Aticaprant 10 mg
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
During DB treatment phase, participants received aticaprant 10 milligrams (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI).
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Subject analysis set title |
FU: Placebo
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants who received placebo and completed DB phase entered the follow-up phase and were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57).
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Subject analysis set title |
FU: Aticaprant 10 mg
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants who received aticaprant 10 mg and completed DB phase entered the follow-up phase and were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57).
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
During DB treatment phase, participants received placebo matching to aticaprant tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (selective serotonin reuptake inhibitor/serotonin–norepinephrine reuptake inhibitor [SSRI/SNRI]). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003. | ||
Reporting group title |
Aticaprant 10 mg
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Reporting group description |
During DB treatment phase, participants received aticaprant 10 milligrams (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003. | ||
Subject analysis set title |
DB: Placebo
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
During DB treatment phase, participants received placebo matching to aticaprant tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI).
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Subject analysis set title |
DB: Aticaprant 10 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
During DB treatment phase, participants received aticaprant 10 milligrams (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI).
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Subject analysis set title |
FU: Placebo
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received placebo and completed DB phase entered the follow-up phase and were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57).
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Subject analysis set title |
FU: Aticaprant 10 mg
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants who received aticaprant 10 mg and completed DB phase entered the follow-up phase and were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57).
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End point title |
Change from Baseline to Day 43 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | ||||||||||||
End point description |
The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in MADRS total score indicates improvement. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1) to Day 43
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo v Aticaprant 10 mg
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Number of subjects included in analysis |
313
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.467 | ||||||||||||
Method |
Mixed Model for Repeated Measures | ||||||||||||
Parameter type |
Least Square Mean Difference | ||||||||||||
Point estimate |
-0.9
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-3.24 | ||||||||||||
upper limit |
1.49 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.2
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End point title |
Percentage of Participants who Achieved Response on Depressive Symptoms Scale Based on MADRS Total Score at Day 43 | ||||||||||||
End point description |
Responders are defined as participants with a greater than or equal to (>=)50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
At Day 43
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline Over Time in MADRS Total Score | |||||||||||||||||||||
End point description |
The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in total score indicates improvement. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants analyzed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29 and 43
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change from Baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) Total Score | ||||||||||||
End point description |
The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD across the 4 domains: hobbies, social activities, food/drink, and sensory experience. The DARS scale measures desire, motivation, effort, and consummatory pleasure. The DARS is rated on a 5-point Likert scale (0=not at all, 1=slightly, 2=moderately, 3=mostly, 4=very much) and responses are summed to generate the total score (ranges from 0 to 68). A lower total score is indicative of greater anhedonia. Positive changes in DARS total score indicate improvement. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Day 43
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline Over Time in DARS Total Score | |||||||||||||||||||||
End point description |
Change from baseline over time in DARS total score is reported. The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD across the 4 domains: hobbies, social activities, food/drink, and sensory experience. The DARS scale measures desire, motivation, effort, and consummatory pleasure. The DARS is rated on a 5-point Likert scale (0=not at all, 1=slightly, 2=moderately, 3=mostly, 4=very much) and responses are summed to generate the total score (range of 0 to 68). A lower total score is indicative of greater anhedonia. Positive changes in DARS total score indicate improvement. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants who were analyzed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, and 43
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change from Baseline to Day 43 in Patient Health Questionnaire, 9-Item (PHQ-9) Total Score | ||||||||||||
End point description |
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) 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. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in PHQ-9 total score indicate improvement. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) to Day 43
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Statistical analysis title |
Statistical Analysis 2 | ||||||||||||
Comparison groups |
Placebo v Aticaprant 10 mg
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Number of subjects included in analysis |
290
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
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Parameter type |
Least Square Mean Difference | ||||||||||||
Point estimate |
-0.8
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-2.21 | ||||||||||||
upper limit |
0.52 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.69
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End point title |
Percentage of Participants With Remission of Depressive Symptoms Based on MADRS Total Score at Day 43 | ||||||||||||
End point description |
Percentage of participants with remission of depressive symptoms based on MADRS total score at Day 43 is reported. Participant is defined as a remitter at a given time point if the MADRS total score is less than or equal to (<=)10 at that time point. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
At Day 43
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline Over Time in the PHQ-9 Anhedonia-specific Item (PHQ-9, item 1) | |||||||||||||||||||||
End point description |
The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition DSM-5 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. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in total score indicate improvement. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants who were analyzed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, Day 29, and Day 43
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Percent Change from Baseline Over Time in Work Productivity and Activity Impairment: Depression (WPAI:D) | ||||||||||||||||||||||||
End point description |
The WPAI:D questionnaire is a validated short instrument that assesses impairment in work and other regular activities over the past 7 days. The WPAI yields four types of scores: (a) Absenteeism (work time missed); (b) Presenteeism (impairment at work / reduced on-the-job effectiveness); (c) Work productivity loss (overall work impairment / absenteeism plus presenteeism); (d) Activity Impairment. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity. Negative changes in score indicates less impairment and greater productivity. As planned overall work impairment (absenteeism plus presenteeism) and activity impairment is reported. Full analysis set (ANH+): all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. 'N' (overall number of participants analyzed)=participants evaluable for this outcome measure; 'n' (number analyzed)=number of participants who were analyzed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 29 and 43
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change from Baseline Over Time in Patient Reported Outcomes Measurement Information System Short Form - Ability to Participate in Social Roles and Activities - 8a (PROMIS-APS 8a) | |||||||||||||||||||||
End point description |
This 8-item measure assesses participants' ability to participate in social roles and activities. The items measures the degree of involvement in social roles, activities, and responsibilities, including work, family, friends, and leisure. Each item is rated on a 5-point ordinal scale including 1=always, 2=usually, 3=sometimes, 4=rarely and 5=never, with higher scores indicating better social functioning. The total scores ranges from 8 to 40 and is transformed using a T-score metric with a mean of 50 and a standard deviation of 10. T-score ranges from 25.9 to 65.4, a higher score indicates better social functioning. Positive change in score indicates improvement. Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall participants analyzed) signifies participants evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants analyzed at specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, and 43
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Percentage of Participants With a Score less than (<) 2 in the PHQ-9 Anhedonia-specific Item (PHQ-9, item 1) at Day 43 | ||||||||||||
End point description |
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 DSM-5 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. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Full analysis set (ANH+) included all adult randomized participants with MDD ANH+ who received at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
At Day 43
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Follow-up (FU) Phase: Percentage of Participants With AEs | ||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Follow-up analysis set included all randomized participants who entered the follow-up phase after the double-blind treatment phase.
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End point type |
Secondary
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End point timeframe |
From Day 44 up to Day 57
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| No statistical analyses for this end point | |||||||||||||
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End point title |
DB Treatment Phase: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | ||||||||||||
End point description |
Percentage of participants with AEs during DB treatment phase are reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs included both serious and non serious adverse events. TEAEs are defined as AEs with onset during the DB Treatment Phase, or AEs that are a consequence of a pre-existing condition that has worsened since baseline (Day 1). Safety analysis set included all randomized participants (adults and elderly) who received at least 1 dose of study intervention.
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End point type |
Secondary
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End point timeframe |
From start of treatment (Day 1) up to Day 43
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
DB treatment phase: start of treatment (Day 1) up to Day 43, FU Phase: From Day 44 up to Day 57
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Adverse event reporting additional description |
DB phase: Safety analysis set included all randomized participants (adults and elderly) who received at least 1 dose of study treatment. FU phase: FU population included all randomized participants who entered the FU phase after the double-blind treatment phase.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
DB: Aticaprant 10 mg
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Reporting group description |
During the DB treatment phase, participants received aticaprant 10 mg tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DB: Placebo
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Reporting group description |
During DB treatment phase, participants received placebo matching to aticaprant tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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09 Aug 2022 |
The overall reason for this amendment was to make updates based on feedback received from interactions with health authorities, key opinion leaders in the MDD field and potential investigational sites involved in the study feasibility, to ensure alignment across the program and to improve patient selection. Minor changes were made throughout the protocol for compliance with updated protocol template text, for clarification, and to correct errors. |
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22 Feb 2023 |
The overall reason for this amendment was to make updates based on feedback received from interactions with health authorities, to ensure alignment across the program and to improve participant selection. Minor changes were made throughout the protocol for clarification and to correct errors. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
