Aticaprant for Depression

(VENTURA-2 Trial)

Recruiting at 151 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: SSRIs, SNRIs

Must not be taking: Ketamine, Esketamine

Disqualifiers: Substance use disorder, Seizures, Suicidal ideation, others

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

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: 6 weeks

710 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if aticaprant, a new potential drug, can improve symptoms of major depressive disorder (MDD) in individuals who haven't fully responded to their current antidepressants. Participants will receive either aticaprant or a placebo, alongside their existing medication, to assess which is more effective. The trial seeks individuals experiencing depression with low interest or pleasure in activities (anhedonia) who are currently taking an SSRI or SNRI medication but still struggle with symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to the potential availability of a new treatment for MDD.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications. In fact, you need to continue taking your current SSRI or SNRI antidepressant at a stable dose to participate.

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

Studies have shown that aticaprant is generally safe when used with antidepressants like SSRIs or SNRIs. Common side effects include headaches, occurring in about 11.8% of those taking aticaprant compared to 7.1% of those on a placebo. Diarrhea was reported at similar rates in both groups. Overall, the treatment appears safe, with most side effects being mild. ^{1 2 3 4 5}

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

Researchers are excited about Aticaprant for depression because it works differently than most standard treatments. While typical antidepressants like SSRIs and SNRIs target serotonin and norepinephrine levels, Aticaprant acts on the kappa opioid receptors in the brain, which are linked to mood regulation. This unique mechanism of action could offer relief for patients who don't respond well to conventional antidepressants and may reduce depressive symptoms more effectively. Additionally, Aticaprant is designed to be taken once daily, making it a convenient option for those seeking a new approach to managing depression.

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

Research has shown that aticaprant, one of the treatments in this trial, when combined with common antidepressants like SSRIs or SNRIs, holds promise for reducing symptoms of depression in people with major depressive disorder (MDD) who haven't improved with antidepressants alone. Studies found that aticaprant targets brain areas related to pleasure, potentially reducing feelings of anhedonia (loss of interest or pleasure). Early clinical results showed a significant decrease in depressive symptoms for those taking aticaprant compared to those taking a placebo. However, further development of aticaprant was stopped because it wasn't effective in later trials. While there were positive results early on, the treatment may not work for everyone. ^{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?

Adults with major depressive disorder (MDD) and moderate-to-severe anhedonia who haven't responded well to current SSRI or SNRI antidepressants. They must have a history of depression, be medically stable, and not have had significant improvement in their symptoms recently.

Inclusion Criteria

BMI 18-40

Currently receiving a SSRI or SNRI and tolerating well

I am currently on an SSRI or SNRI for depression and it's working well.

Exclusion Criteria

You have been diagnosed with HIV/AIDS

You have been diagnosed with Psychosis

You have been diagnosed with Seizures

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 or placebo once daily for 42 days in addition to their current antidepressant therapy

6 weeks

Regular visits for safety and efficacy assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Open-label extension (optional)

Participants may opt into a separate 52-week open-label long-term safety study

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aticaprant

Trial Overview The trial is testing Aticaprant as an add-on treatment compared to a placebo. Participants will continue their current antidepressant therapy and either receive Aticaprant or a placebo to see if it better improves symptoms of depression.

How Is the Trial Designed?

Group I: Aticaprant Experimental Treatment 1 Intervention

Participants will receive Aticaprant 10 milligrams (mg) tablet orally, once daily for 42 days during double-blind (DB) treatment phase in addition to their current antidepressant selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy. Participants who will complete the DB treatment phase (Day 43) may be eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003.

Group II: Placebo Placebo Group 1 Intervention

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

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

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]

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]

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 ...