aticaprant · program

Aticaprant for Major depressive disorder

DiscontinuedDiscontinuedJohnson & Johnson (JNJ)

Adjunctive (add-on to SSRI/SNRI) MDD program. Phase 2a (NCT03559192) was positive: aticaprant 10 mg significantly reduced MADRS vs placebo with a favorable safety profile (Schmidt et al., Neuropsychopharmacology 2024). The Phase 3 VENTURA program (efficacy studies VENTURA-1 NCT05455684 and VENTURA-2 NCT05550532, plus long-term safety/extension studies NCT05518149 and NCT06514742) failed to show sufficient efficacy in the target population. On 2025-03-06, Johnson & Johnson announced discontinuation of the aticaprant MDD program; the drug remained safe and well-tolerated with no new safety signals.

Data current as of

Development timeline

DiscontinuedMar 2025
  1. missedPhase 3 VENTURA program failed: J&J discontinued aticaprant for MDD on 2025-03-06 for insufficient efficacy; drug remained safe and well tolerated.↗
Phase 3Jun 2022 – Apr 2024
  1. metPhase 2a (NCT03559192) positive: adjunctive aticaprant 10 mg reduced MADRS vs placebo at Week 6 (LSMD -2.1; p=0.044, 1-sided); well tolerated.↗
  2. Phase 3 VENTURA program initiated (VENTURA-1 NCT05455684 first patient).
Phase 2May 2020
  1. Phase 2a adjunctive MDD study (NCT03559192) completed; positive on primary MADRS endpoint vs placebo.↗

Readouts

  • 2025-03-06ReportedTopline datamissed

    Phase 3 VENTURA program failed: J&J discontinued aticaprant for MDD on 2025-03-06 for insufficient efficacy; drug remained safe and well tolerated. ↗

  • 2024-04-22ReportedFull resultsmetNCT03559192

    Phase 2a (NCT03559192) positive: adjunctive aticaprant 10 mg reduced MADRS vs placebo at Week 6 (LSMD -2.1; p=0.044, 1-sided); well tolerated. ↗

Clinical trials in Major depressive disorder

NCT06514742Phase 3Discontinuedn=101

Aticaprant 10 mg as Adjunctive Therapy in Adults With MDD With Moderate-to-severe Anhedonia and Long-term Extension Treatment

Started Jun 2024· Primary completion Apr 2025· 📍 84 sites across 9 countries (United States, Hungary, Spain, Finland)

terminatedprimaryStudy outcome

Terminated early due to insufficient efficacy of the aticaprant Phase 3 program (sponsor decision, March 2025).

NCT05550532Phase 3Completedn=444

VENTURA-2: Aticaprant 10 mg as Adjunctive Therapy in Adults With MDD With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy

Started Dec 2022· Primary completion Nov 2024· 📍 131 sites across 14 countries (United States, China, South Korea, Argentina)

missedprimaryChange from baseline in MADRS total score vs placebo (adjunctive, MDD with anhedonia)

Part of the Phase 3 VENTURA program that failed to demonstrate sufficient efficacy in the target population; contributed to J&J's March 2025 discontinuation decision.

NCT05518149Phase 3Discontinuedn=871

Open-label, Long-term Safety and Efficacy Study of Aticaprant as Adjunctive Therapy in Adult and Elderly Participants With MDD

Started Sept 2022· Primary completion Apr 2025· 📍 234 sites across 21 countries (United States, Argentina, China, Czechia)

NCT05455684Phase 3Completedn=513

VENTURA-1: Aticaprant 10 mg as Adjunctive Therapy in Adults With MDD With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy

Started Jun 2022· Primary completion Sept 2024· 📍 120 sites across 13 countries (United States, Spain, Brazil, Argentina)

missedprimaryChange from baseline in MADRS total score vs placebo (adjunctive, MDD with anhedonia)

Part of the Phase 3 VENTURA program that failed to demonstrate sufficient efficacy in the target population; contributed to J&J's March 2025 discontinuation decision.

NCT03559192Phase 2Completedn=181

A Phase 2a Study Investigating Efficacy, Safety, Tolerability and Pharmacokinetics of JNJ-67953964 (Aticaprant) in Subjects With Major Depressive Disorder

Started Jul 2018· Primary completion May 2020· 📍 53 sites across 6 countries (United States, Russia, Ukraine, United Kingdom)

metprimaryChange from baseline in MADRS total score at Week 6 vs placebo (eITT) — LS mean difference -2.1 (effect size 0.23) (0.044 (1-sided))

Adjunctive aticaprant 10 mg significantly reduced depressive symptoms vs placebo at Week 6 on MADRS; met the prespecified primary endpoint. Well tolerated with no significant safety signals.

NCT01913535Phase 2Discontinuedn=8

Proof-of-Concept Trial of CERC-501 Augmentation of Antidepressant Therapy in Treatment-Resistant Depression

Started Sept 2013· Primary completion Jan 2016· 📍 4 sites across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
Aticaprant oral tablet
10 mg once daily (Phase 3 dose in MDD with anhedonia); Phase 1/2 explored 4-25 mg
OralOnce dailyt½ 35 h · Tmax 1.5 h · F 25%

Mechanism of action (compound-wide)

Selective antagonist of the kappa-opioid receptor (KOR / OPRK1). Potent KOR binding (Ki ~0.81 nM) with ~30-fold selectivity over mu and delta opioid receptors; blocks KOR/dynorphin signaling implicated in dysphoria, stress and anhedonia, with the therapeutic hypothesis of restoring reward/dopaminergic function in depression.

TargetActionAffinity
KORprimaryOPRK1AntagonistKi 0.81 nMⓘ

← Full aticaprant compound page (identity, identifiers, all indications)

Sources

  1. Aticaprant — Wikipedia
  2. Aticaprant 10 mg adjunctive in MDD with anhedonia + extension (NCT06514742) — ClinicalTrials.gov
  3. Efficacy and safety of aticaprant adjunctive to SSRI/SNRI in MDD: a phase 2 randomized, double-blind, placebo-controlled study (Schmidt et al., Neuropsychopharmacology 2024;49(9):1437-1447) — Neuropsychopharmacology (PubMed)
  4. clinicaltrials.gov — clinicaltrials.gov
  5. J&J drops Phase III MDD programme (VENTURA / aticaprant) due to lack of efficacy — Clinical Trials Arena
  6. LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist (Rorick-Kehn et al., Neuropharmacology 2014;77:131-144) — Neuropharmacology (PubMed)
  7. Open-label long-term safety/efficacy of aticaprant in MDD (NCT05518149) — ClinicalTrials.gov
  8. Phase 2a aticaprant (JNJ-67953964) in MDD (NCT03559192) — ClinicalTrials.gov
  9. VENTURA-1: aticaprant 10 mg adjunctive in MDD with anhedonia (NCT05455684) — ClinicalTrials.gov
  10. VENTURA-2: aticaprant 10 mg adjunctive in MDD with anhedonia (NCT05550532) — ClinicalTrials.gov