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

Trial Summary

What is the purpose of this trial?

This trial is testing aticaprant to see if it can help adults with major depressive disorder and anhedonia who haven't responded well to other antidepressants. Aticaprant works by blocking certain receptors in the brain to potentially improve depressive symptoms.

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.

How does the drug Aticaprant differ from other depression treatments?

Aticaprant is unique because it is a neurokinin-1 (NK1) receptor antagonist, which means it works by blocking specific receptors in the brain that are involved in mood regulation. This mechanism is different from most traditional antidepressants, which typically target serotonin or norepinephrine pathways. ^{1 2 3 4 5}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. [2018]

2. England 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. [2022]

3. India 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. [2022]

4. Germany 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. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Antiemetic studies on the NK1 receptor antagonist aprepitant. [2019]