Aticaprant for Depression

(VENTURA-7 Trial)

No longer recruiting at 45 trial locations

Overseen By Study Contact

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must be taking: SSRIs, SNRIs

Disqualifiers: Psychotic disorder, Bipolar, Substance use, others

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: 74

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, aticaprant, when combined with an existing antidepressant. It targets individuals with major depressive disorder (MDD) who experience moderate to severe anhedonia and have not found much success with their current antidepressant, specifically SSRIs or SNRIs. Suitable participants are those on a stable dose of one of these antidepressants but continue to struggle with symptoms. As a Phase 3 trial, this study is the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment for MDD.

Do I have to stop taking my current medications for this trial?

No, you don't have to stop taking your current medications. In fact, you need to continue taking your current SSRI or SNRI antidepressant at a stable dose for at least 6 weeks before joining the trial.

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

Research has shown that aticaprant is generally safe for people with major depressive disorder. When combined with common antidepressants like SSRIs or SNRIs, it maintains a good safety record, indicating that participants did not encounter major safety issues. Although some unwanted effects were reported, they were not serious. This suggests that aticaprant can be safely used alongside regular antidepressants. ^{1 2 3 4 5}

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

Unlike the standard antidepressants, which typically target neurotransmitters like serotonin, norepinephrine, or dopamine, Aticaprant works by blocking the kappa opioid receptor. This novel mechanism of action could offer a new pathway for alleviating depression symptoms. Researchers are particularly excited because Aticaprant might provide relief for patients who haven't responded well to traditional antidepressants. Additionally, this fresh approach could potentially lead to faster and more effective results, offering hope to those struggling with this challenging condition.

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

Research has shown that aticaprant, when combined with other antidepressants, might reduce symptoms of depression in individuals with major depressive disorder who haven't responded well to common treatments like SSRIs or SNRIs. Studies found that aticaprant can significantly lower feelings of depression by affecting certain brain receptors related to mood and pleasure. However, Johnson & Johnson discontinued its development for depression due to poor performance in later research. These findings suggest mixed results for aticaprant in treating depression. In this trial, participants will receive either aticaprant or a placebo to further evaluate its effectiveness. ^{1 2 5 6 7}

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 still feel a significant lack of pleasure (anhedonia) despite being on current antidepressants like SSRIs or SNRIs. Participants should have an inadequate response to these treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either aticaprant or placebo along with an antidepressant therapy

6 weeks

Up to Day 43

Open-label Treatment

Participants receive aticaprant as an adjunctive therapy

31 weeks

Up to Week 31

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aticaprant

Trial Overview The study tests Aticaprant, given alongside standard antidepressants, against a placebo (a substance with no active drug). It aims to see if Aticaprant can better improve symptoms of depression in those not helped enough by their current medication.

How Is the Trial Designed?

Group I: Aticaprant Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

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

Upadacitinib, a selective JAK1 inhibitor, demonstrated an oral bioavailability of approximately 80% for its extended-release formulation compared to the immediate-release version, based on a pharmacokinetic analysis of 11,658 plasma concentrations from 1,145 subjects across multiple studies.

The study found that while certain factors like sex and renal function can affect drug levels in the body, these variations are not expected to lead to clinically significant changes in the drug's effectiveness or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials. Nader, A., Stodtmann, S., Friedel, A., et al.[2021]

A retrospective analysis of 14,670 reports found that montelukast is associated with a significant number of psychiatric disorders in children and adolescents, with 2630 cases specifically linked to these age groups.

The study revealed that suicidal behavior was notably over-represented among children and adolescents taking montelukast, indicating a need for increased awareness and monitoring of neuropsychiatric side effects in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric Disorders and Montelukast in Children: A Disproportionality Analysis of the VigiBase(®). Aldea Perona, A., García-Sáiz, M., Sanz Álvarez, E.[2021]

The FDA has mandated a boxed warning for Singulair (montelukast) due to concerns about neuropsychiatric adverse events, particularly for patients using it for allergic rhinitis, limiting its use to those who do not respond to other treatments.

Despite the concerns, the asthma indication for montelukast remains unchanged, indicating that the benefits for asthma patients are considered to outweigh the risks based on the available data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Boxed Warning for Montelukast: The FDA Perspective. Clarridge, K., Chin, S., Eworuke, E., et al.[2021]

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]

Tofacitinib at doses of 3 mg or higher taken twice daily showed significant efficacy in treating active rheumatoid arthritis, with ACR20 response rates reaching up to 71.9% by week 12, compared to 22.0% for placebo.

The treatment was generally well-tolerated, with manageable side effects, the most common being urinary tract infections and diarrhea, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Fleischmann, R., Cutolo, M., Genovese, MC., et al.[2022]

Tofacitinib, an oral Janus kinase inhibitor for ulcerative colitis, was studied in 1,096 patients across multiple trials, showing consistent pharmacokinetics with a half-life of about 3.05 hours and no significant changes in drug exposure during treatment.

The study found that while factors like age, sex, and race influenced drug clearance and distribution, these effects were not clinically significant, meaning no dose adjustments are necessary based on these covariates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Tofacitinib in Patients With Moderate to Severe Ulcerative Colitis. Vong, C., Martin, SW., Deng, C., et al.[2021]

Over a 30-year period, 1366 reports of adverse drug reactions (ADRs) associated with antidepressants in children and adolescents were identified, highlighting a significant prevalence of neuropsychiatric issues such as sleepiness, agitation, and suicidal thoughts.

The study revealed a concerning trend of increased reporting of suicidal thinking and behavior after 2003, suggesting that black box warnings may have influenced both reporting practices and the use of antidepressants in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions in infants, children and adolescents exposed to antidepressants: a French pharmacovigilance study. Barthez, S., Revet, A., Chouchana, L., et al.[2021]

Severe cutaneous adverse drug reactions (CADRs) were found to be more common in patients treated with specific psychotropic medications, particularly clomipramine, maprotiline, carbamazepine, and lamotrigine, highlighting the need for careful monitoring of these drugs.

Women, especially those under 50 years old, were identified as being more vulnerable to CADRs, with factors such as female sex and the use of certain medications like maprotiline and lamotrigine significantly increasing the risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous adverse drug reactions to psychotropic drugs and their risk factors - a case-control study. Greil, W., Zhang, X., Stassen, H., et al.[2019]

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 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]

Tofacitinib, an oral Janus kinase inhibitor, significantly improved patient-reported outcomes in individuals with active ulcerative colitis, particularly at the 15 mg dose, compared to placebo after 8 weeks of treatment.

Patients who achieved endoscopic remission reported even higher satisfaction and quality of life scores, indicating that tofacitinib not only helps with clinical symptoms but also enhances overall patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes. Panés, J., Su, C., Bushmakin, AG., et al.[2022]

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]

Elderly patients with renal failure taking dabigatran are at a higher risk of bleeding, highlighting the need for careful monitoring in this population.

Agomelatine is associated with elevated liver enzymes, indicating a potential safety concern that requires attention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacovigilance update]. Livio, F.[2015]

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]

Tofacitinib, an oral JAK inhibitor, was studied in 2981 patients with psoriasis over a period of up to 56 weeks, revealing that its pharmacokinetics can be effectively modeled using a one-compartment model that accounts for various patient factors.

The study found that only creatinine clearance (CrCl) significantly affected drug exposure, indicating that no dosing adjustments are necessary based on age, sex, race, or other baseline characteristics, except for patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Characteristics of Tofacitinib in Adult Patients With Moderate to Severe Chronic Plaque Psoriasis. Ma, G., Xie, R., Strober, B., et al.[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 ...

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01913535?term=LY2456302%26rank=1

NCT01913535 | Proof-of-Concept Trial of CERC-501 ... This study is looking at the efficacy, rapidity, safety, and tolerability of two doses of oral CERC-501 for treating patients with treatment resistant ...