Icalcaprant · program

Icalcaprant for Major depressive disorder

Phase 2RecruitingAbbVie Inc. (ABBV)

Phase 2, multicenter, 6-week, double-blind, placebo-controlled study of icalcaprant in adults with major depressive disorder (NCT07276997), evaluating two oral once-daily doses versus placebo on change from baseline in MADRS total score. Approximately 195 participants across ~35 North American sites; recruiting as of 2026. No designations identified.

Data current as of

Development timeline

Phase 2Dec 2025 – Sept 2027
  1. UpcomingAnticipated Phase 2 topline (MADRS change from baseline at week 6) for icalcaprant in major depressive disorder
  2. Phase 2 MDD efficacy/safety trial (NCT07276997) initiated; actual study start 2025-12-18.
Phase 1Nov 2021
  1. First-in-human Phase 1 single/multiple ascending dose trial of CVL-354 in healthy participants (NCT05138653) under Cerevel Therapeutics; supportive PET target-occupancy (NCT05547542) and PK trials followed.

Readouts

  • 2H 2027AnticipatedTopline dataNCT07276997

    Anticipated Phase 2 topline (MADRS change from baseline at week 6) for icalcaprant in major depressive disorder

Clinical trials in Major depressive disorder

NCT07276997Phase 2Recruitingn=195

A Phase 2, Multicenter, 6-Week, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Icalcaprant in Subjects With Major Depressive Disorder

Started Dec 2025· Primary completion Sept 2027· 📍 33 sites across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
Icalcaprant oral capsule
Oral capsule dosed once daily; multiple-ascending-dose Phase 1 tested 10, 25, 50, and 85 mg QD for up to 14 days; Phase 2 MDD tests two once-daily oral doses over 6 weeks
OralOnce daily—

Mechanism of action (compound-wide)

Selective antagonist of the kappa opioid receptor (KOR / OPRK1), a class A GPCR. It is also a weaker antagonist of the mu opioid receptor (MOR / OPRM1), with approximately 31-fold lower affinity and approximately 27-fold lower inhibitory potency at MOR relative to KOR. KOR antagonism is the proposed antidepressant mechanism (blockade of dynorphin/KOR signaling implicated in dysphoria and anhedonia).

TargetActionAffinity
KORprimaryOPRK1Antagonist—ⓘ
MOROPRM1Antagonist—ⓘ

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

Sources

  1. A Phase 2 Study to Evaluate the Efficacy and Safety of Icalcaprant in Subjects With Major Depressive Disorder — ClinicalTrials.gov
  2. A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants — ClinicalTrials.gov
  3. Icalcaprant — Wikipedia