What side effects are associated with this type of intervention?

Common treatments for Major Depressive Disorder (MDD) include SSRIs (e.g., fluoxetine, sertraline) and SNRIs (e.g., venlafaxine, duloxetine). These medications are generally well-tolerated but can cause side effects such as nausea, insomnia, sexual dysfunction, and increased anxiety. Tricyclic antidepressants (TCAs) and atypical antidepressants like mirtazapine and trazodone may cause sedation, weight gain, and dry mouth. Aticaprant, a selective kappa opioid receptor antagonist, is being studied as an adjunctive therapy for MDD, but specific side effects for this class are not well-documented yet. Generally, all antidepressants should be used cautiously in patients with central nervous system diseases due to the potential for lowering the seizure threshold.

What prior FDA approvals exist?

The FDA has approved several classes of medications for the treatment of Major Depressive Disorder (MDD), including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine, and atypical antidepressants like bupropion. While Aticaprant, a selective kappa opioid receptor antagonist, is currently being studied, there are no FDA-approved treatments in this specific class for MDD. The focus has traditionally been on medications that modulate serotonin and norepinephrine pathways.

What other types of research exist?

Promising novel alternatives to Aticaprant for MDD patients include CERC-501 (another kappa opioid receptor antagonist) and triple reuptake inhibitors, which target serotonin, norepinephrine, and dopamine reuptake. These alternatives are in development and have shown potential in clinical trials.

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Aticaprant for Major Depressive Disorder (VENTURA-1 Trial)

Phase 3

Recruiting

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and baseline

Meet Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) diagnostic criteria for recurrent or single episode 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). Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age

Must not have

Has had in the current episode an inadequate response to adequate course of intravenous or intranasal ketamine or esketamine, electroconvulsive therapy, vagal nerve stimulation, or deep brain stimulation device

Have had in the current depressive episode, no response (treatment failure) to 5 or more antidepressant treatments including the current SSRI/SNRI (that is, the one presumed to be continued in the treatment phase) assessed using the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to day 57

Awards & highlights

Pivotal Trial

Summary

This trial is testing aticaprant to see if it can help people with major depressive disorder who still feel very down and don't enjoy things despite taking other antidepressants. The study focuses on adults who haven't responded well to their current treatments. Aticaprant works by blocking a specific brain receptor, which might help improve their mood and reduce depressive symptoms.

Who is the study for?

Adults with major depressive disorder and moderate-to-severe anhedonia not responding well to current SSRI or SNRI antidepressants. They must have been on a stable dose for at least 6 weeks, have no history of seizures or recent suicidal behavior, and cannot have certain other mental health diagnoses like bipolar disorder or substance use disorders.

What is being tested?

The trial is testing Aticaprant as an add-on treatment to see if it improves symptoms in patients who haven't responded enough to their current antidepressant therapy. Participants will either receive Aticaprant or a placebo alongside their usual medication.

What are the potential side effects?

While the specific side effects of Aticaprant are not listed here, common side effects from similar medications may include nausea, headache, dizziness, dry mouth, sleep disturbances, and changes in appetite or weight.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My health is stable based on recent exams and tests.

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I have been diagnosed with major depression without psychosis, first occurring before I was 55.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My current treatment with ketamine, ECT, VNS, or DBS hasn't worked well.

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I have tried 5 or more antidepressants without success for my current depressive episode.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to day 57

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to day 57

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to day 57 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score to Day 43

Secondary study objectives

Change from Baseline in DARS Total Score Over Time

Change from Baseline in Dimensional Anhedonia Rating Scale (DARS) Total Score to Day 43

Change from Baseline in MADRS Total Score over Time

+7 more

Side effects data

From 2017 Phase 2 trial • 163 Patients • NCT02218736

29%

Diarrhea

22%

Headache

22%

Puritus

20%

Suicidal Ideation

13%

Rash

13%

Anxiety

13%

Depression

13%

Dizziness

Pollakiuria

Dry Skin

Dry Mouth

Insomnia

Tinnitus

Vission Blurred

Constipation

Dysuria

Nausea

Fatigue

Coordination Abnormal

Disturbance in Attention

Dizziness postural

Non-cardiac chest pain

Sinus congestion

Irritability

Malaise

Hyperhidrosis

Viral infection

Mood altered

Costochondritis

Initial insomnia

Urinary track infeciton

Gastrointestinal disorder

Syncope

Tendon rupture

Chest pain

Herpes Zoster

Back Pain

Restlessness

Libido decreased

Blepharitis

Panic attack

Chest discomfort

Anal pruritus

Arthralgia

Hypersomnia

Asthenia

Muscle twitching

Nasopharyngitis

Self-injurious ideation

100%

80%

60%

40%

20%

Study treatment Arm

CERC-501

Placebo

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: AticaprantExperimental Treatment1 Intervention

Participants will receive aticaprant tablets orally once daily for 42 days during double-blind treatment phase in addition to the current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003).

Group II: PlaceboPlacebo Group1 Intervention

Participants will receive matching placebo orally once daily for 42 days during double-blind treatment phase in addition to their current antidepressant (SSRI/SNRI) therapy. Participants who will complete the double-blind treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study (67953964MDD3003).

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Major Depressive Disorder (MDD) include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which work by increasing the levels of serotonin and norepinephrine in the brain, respectively. These neurotransmitters are crucial for mood regulation. Aticaprant, a selective kappa opioid receptor antagonist, represents a different approach by targeting the kappa opioid receptors, which are involved in stress and mood regulation. This mechanism is particularly relevant for MDD patients with anhedonia and inadequate response to traditional antidepressants, as it offers a novel pathway to potentially alleviate depressive symptoms and improve overall treatment outcomes.