Aticaprant for Depression

(VENTURA-LT Trial)

Recruiting at 219 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: SSRIs, SNRIs

Disqualifiers: Noncompliance, Allergies to aticaprant, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

840 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term safety and tolerability of aticaprant, a new medication for people with major depressive disorder (MDD). Participants will continue their current antidepressant (either an SSRI or SNRI) while adding aticaprant to their treatment. The study targets individuals who have faced challenges with their current depression treatment. Ideal participants have already been on an antidepressant that hasn't fully worked and are experiencing ongoing depression symptoms without significant improvement. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the approval of a potentially effective new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that participants should not take any prohibited medication or food supplements. You can continue taking your current antidepressant (SSRI or SNRI) as aticaprant is used as an additional treatment.

Is there any evidence suggesting that aticaprant is likely to be safe for humans?

Research has shown that aticaprant is generally safe and well-tolerated. In earlier studies, the most common side effects were mild, such as headaches and diarrhea, and were not serious. Another study found that aticaprant can be safely used with common antidepressants like SSRIs or SNRIs. Overall, the safety results for aticaprant are encouraging for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Unlike the standard depression treatments that primarily involve selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), Aticaprant offers a fresh approach by targeting the kappa opioid receptor. This unique mechanism is believed to potentially modulate mood and stress differently, possibly providing relief for patients who don't respond well to conventional antidepressants. Researchers are enthusiastic about Aticaprant because it could offer a novel pathway for treating depression, especially for those who have not benefited from existing therapies.

What evidence suggests that aticaprant might be an effective treatment for major depressive disorder?

Research has shown that aticaprant, when combined with an existing antidepressant, has potential in reducing symptoms of major depressive disorder (MDD) in some studies. It affects certain brain receptors believed to influence mood. Some studies noted a decrease in depressive symptoms and improvements in brain areas linked to feeling pleasure. However, aticaprant's development for MDD was halted due to insufficient effectiveness in later trials, resulting in mixed outcomes regarding its ability to treat depression. Participants in this trial will receive Aticaprant 10 milligrams, once daily, alongside their current SSRI/SNRI therapy. ^{1 2 4 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with Major Depressive Disorder who haven't had enough improvement after trying 1-3 antidepressants. They must have a certain score on a depression rating scale and meet specific diagnostic criteria without psychotic features. Employees of the study or those with allergies to aticaprant can't participate.

Inclusion Criteria

Have you tried at least 1 antidepressant that hasn't worked?

Have you been diagnosed with Depression?

Are you currently on a Neurotransmitter Uptake Inhibitor?

Exclusion Criteria

Have you tried more than 2 antidepressants that haven't worked?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Aticaprant 10 mg once daily, orally in addition to their current antidepressant therapy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Open-label extension

Participants may continue to receive Aticaprant as adjunctive therapy to assess long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Aticaprant

Trial Overview The trial tests Aticaprant's long-term safety and effectiveness when added to current SSRI or SNRI treatments in patients with depression. It aims to see if this combination helps people who didn't respond well to previous medications.

How Is the Trial Designed?

Group I: Aticaprant 10 mg Experimental Treatment 1 Intervention

Participants will enter this study directly or after completing double-blind phase of studies 67953964MDD3001 or 67953964MDD3002 and will receive Aticaprant 10 milligrams (mg), once daily, orally in addition to the current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy on Day 1 up to 52 weeks.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Aprepitant, the first NK1 receptor antagonist approved for preventing chemotherapy-induced nausea and vomiting (CINV), is effective with a dosing regimen of 125 mg on day 1 and 80 mg on days 2 and 3, showing consistent plasma levels and good tolerability.

The bioavailability of aprepitant is not significantly affected by food intake, allowing it to be taken independently of meals, which simplifies its administration for patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. Majumdar, AK., Howard, L., Goldberg, MR., et al.[2018]

In a phase 2 study involving 236 outpatients with major depressive disorder, the combination of aprepitant and paroxetine did not show a significant improvement in depression scores compared to paroxetine alone after 6 weeks.

Patients taking the combination therapy experienced more adverse events than those on monotherapy, indicating that adding aprepitant may not be beneficial and could increase side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of an NK1 receptor antagonist to an SSRI did not enhance the antidepressant effects of SSRI monotherapy: results from a randomized clinical trial in patients with major depressive disorder. Ball, WA., Snavely, DB., Hargreaves, RJ., et al.[2022]

In a randomized trial comparing 5 mg olanzapine and aprepitant for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin, both medications showed similar effectiveness in total protection rates during acute, delayed, and overall phases, with no significant differences in outcomes.

While both treatments were effective, olanzapine was associated with increased sedation as a side effect, while aprepitant led to constipation, suggesting that olanzapine may offer a cost-effective alternative for managing CINV despite its sedative effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of the Efficacy of 5 mg Olanzapine and Aprepitant in the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting. Liu, G., Jin, Y., Jiang, Y., et al.[2022]

In a phase 3 trial involving 196 patients receiving carboplatin, the fixed antiemetic combination NEPA (netupitant and palonosetron) demonstrated similar efficacy to the standard regimen of aprepitant, palonosetron, and dexamethasone in preventing nausea and vomiting, with complete response rates ranging from 80% to 93%.

Both NEPA and aprepitant showed comparable rates of no significant nausea, suggesting that NEPA is an effective alternative for managing chemotherapy-induced nausea and vomiting in carboplatin-treated patients, supporting the recommendation for NK1 receptor antagonists in treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy benefit of an NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens. Jordan, K., Gralla, R., Rizzi, G., et al.[2018]

Aprepitant, an NK1 receptor antagonist, significantly improves the prevention of chemotherapy-induced nausea and vomiting (CINV) when added to standard antiemetic therapy, with complete response rates increasing from 43.3%-52.3% to 58.8%-71% in clinical trials involving multiple cycles of highly emetogenic chemotherapy.

The addition of aprepitant is well tolerated, with adverse events similar to standard therapy, and it effectively reduces the impact of CINV on patients' daily lives, making it a valuable option for patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic studies on the NK1 receptor antagonist aprepitant. Stoutenburg, JP., Raftopoulos, H.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38649428/

Efficacy and safety of aticaprant, a kappa receptor ... In this study of participants with MDD and inadequate response to SSRI/SNRI, adjunctive treatment with aticaprant significantly reduced depressive symptoms ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06514742

NCT06514742 | A Study of Aticaprant 10 mg as Adjunctive ... The purpose of this study is to evaluate how well aticaprant works as compared with placebo when given along with an antidepressant therapy in improving the ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/14728214.2024.2345645

Full article: Aticaprant: (a κ-opioid receptor antagonist) for ... The observed impact of Aticaprant on brain areas associated with pleasure and the reduction in clinical anhedonia, assessed by the Snaith-Hamilton Pleasure ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724010863

Preclinical and clinical efficacy of kappa opioid receptor ... Aticaprant and navacaprant reduced depressive symptoms in persons with MDD. •. Treatment-emergent adverse events were mild in severity and ...

5. en.wikipedia.org en.wikipedia.org/wiki/Aticaprant

Aticaprant In March 2025, Johnson & Johnson discontinued development of aticaprant for major depressive disorder due to lack of effectiveness in phase III trials.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38969753/

Aticaprant, a kappa opioid receptor antagonist, and the ... Tolerability and safety were reassuring. These promising results of the co-administration of aticaprant to an SSRI/SNRI in depressed patients ...