E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder (MDD) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025453 |
E.1.2 | Term | Major depressive disorder NOS |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 MDD with moderate-to-severe anhedonia (ANH+) who have had an inadequate response to current antidepressant therapy with an SSRI or SNRI. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of adjunctive aticaprant 10 mg compared with placebo in improving anhedonia in adult participants with MDD ANH+ who have had an inadequate response to current antidepressant therapy with an SSRI or SNRI |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, aged 18 to 74 years of age, inclusive. - Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening and baseline - Be medically stable on the basis of clinical laboratory tests performed at screening - Meet DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age. Male or female, aged 18 to 74 years of age, inclusive. - Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening and baseline - Be medically stable on the basis of clinical laboratory tests performed at screening - Meet DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age. - Have had an inadequate response to at least 1 oral antidepressant treatment, administered at an adequate dose (at or above the minimum therapeutic dose per MHH ATRQ) and duration (at least 6 weeks) in the current episode of depression. - Is currently receiving and tolerating well a SSRI/SNRI for depressive symptoms at screening, at a stable dose for at least 6 weeks - Have a HDRS-17 total score of 20 or higher at the first and second screening interviews and must not demonstrate a clinically significant improvement between the first and the second independent HDRS-17 assessments For a full list of inclusion criteria, please refer to study protocol. |
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E.4 | Principal exclusion criteria |
-- Have had in the current depressive episode, no response (treatment failure) to 5 or more antidepressant treatments including the current SSRI/SNRI (ie, the one presumed to be continued in the treatment phase) assessed using the MGH ATRQ. - Has one or more of the following diagnoses: *A DSM-5 diagnosis (which has been the primary focus of psychiatric treatment within the past 2 years)of any of the following: panic disorder, generalized anxiety disorder, social anxiety disorder, specific phobia. * current (in the past year) DSM-5 diagnosis of: obsessive-compulsive disorder, post-traumatic stress disorder, anorexia nervosa, bulimia nervosa * A current or prior (lifetime) DSM-5 diagnosis of: a psychotic disorder or MDD with psychotic features, bipolar or related disorders, intellectual disability, autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, narcissistic personality disorders, somatoform disorders. - Has a history or evidence of clinically meaningful noncompliance with current antidepressant therapy. - 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 had in the current episode an inadequate response to adequate course of intravenous or intranasal ketamine or esketamine, electroconvulsive therapy (i.e, at least 7 treatments), vagal nerve stimulation, or deep brain stimulation device - Has a current homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 3 months prior to the start of the screening phase For full list of exclusion criteria, please refer to study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 15, Day 29, Day 43 |
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E.5.2 | Secondary end point(s) |
Change from baseline to Day 43 in Dimensional Anhedonia Rating Scale (DARS) total score. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, Day 15, Day 29, Day 43 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 51 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
United States |
Belgium |
Bulgaria |
Czechia |
Hungary |
Italy |
Poland |
Portugal |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is considered as the last scheduled study assessment shown in the schedule of assessments for the last participant in the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |