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NCT Number: NCT07284667

ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response

The goal of this clinical trial is to learn if ACP-211 can help treat adults with major depressive disorder (MDD) who have not improved with antidepressant therapy (ADT), including those with treatment resistant depression (TRD).

The main questions the study aims to answer are:

* Does ACP-211 work better than a placebo (a look-alike capsule with no medicine) to reduce symptoms of depression? * What adverse events do participants have when taking ACP-211?

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Key information

Conditions

Major Depressive Disorder (MDD) Depressive Disorder Depressive Disorder, Major Depressive Disorder, Treatment-Resistant Mental Disorders Mood Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults ≥18 and ≤65 years of age
  • Provides written informed consent
  • Clinical diagnosis of MDD
  • History of inadequate response to at least two antidepressants, with at least one inadequate response documented during the current episode
  • Currently treated with an approved antidepressant at a stable dose prior to Screening
  • MADRS total score ≥28, CGI-S score ≥4 , and QIDS-SR16 score ≥16 at Screening and Baseline
  • Females of childbearing potential must have a negative pregnancy test and agree to use acceptable contraception; males must agree to use barrier protection and refrain from sperm donation

Exclusion criteria

  • Current diagnosis of certain personality disorders or persistent depressive disorder
  • Recent substance use disorders, excluding caffeine or nicotine
  • Active suicidal risk or recent suicidal attempt
  • History of schizophrenia, psychotic disorders, bipolar disorder, or MDD with psychotic features
  • Current treatment requirement for PTSD, acute stress disorder, panic disorder, or OCD
  • History of neuroleptic malignant syndrome, serotonin syndrome, or epilepsy (except single febrile seizure in infancy)
  • Allergy or sensitivity to ketamine or esketamine
  • Significant cardiovascular disease
  • Positive history of hepatitis B, hepatitis C, or HIV infection
  • Unstable diabetes or uncontrolled medical conditions
  • Positive urine drug test for an illicit drug or cannabis
  • Received neuromodulation therapies (ECT, TMS, VNS, DBS) in the current depressive episode
  • Recent initiation or change in psychotherapy

Additional inclusion/exclusion criteria apply. Participants will be evaluated at Screening to ensure that all criteria for study participation are met.

Treatment and study plan

ACP-211

Drug

ACP-211 monotherapy

Placebo

Drug

Placebo control

Primary outcomes

  1. Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Day 28

    Time frame: Baseline and Day 28

    The MADRS is a clinician-rated scale that assesses the severity of depressive symptoms. It consists of 10 items, each scored from 0 (no symptoms) to 6 (severe symptoms), resulting in a total score range of 0 to 60. Higher scores indicate greater depression severity.

Secondary outcomes

  1. Change From Baseline in MADRS Total Score at Day 2

    Time frame: Baseline and Day 2 (24 hours postdose)

    The MADRS is a clinician-rated scale that assesses the severity of depressive symptoms. It consists of 10 items, each scored from 0 (no symptoms) to 6 (severe symptoms), resulting in a total score range of 0 to 60. Higher scores indicate greater depression severity.

  2. Change From Baseline in MADRS Total Score at Scheduled Postbaseline Visits

    Time frame: Baseline through Day 28

  3. Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Scheduled Postbaseline Visits

    Time frame: Baseline through Day 28

    The CGI-S is a clinician-rated assessment of illness severity scored on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). Higher scores indicate greater illness severity.

  4. Proportion of Subjects in Remission at Scheduled Postbaseline Visits (MADRS ≤10)

    Time frame: Up to Day 28

  5. Proportion of Subjects With Response at Scheduled Postbaseline Visits (≥50% Reduction From Baseline in MADRS Total Score)

    Time frame: Up to Day 28

  6. Proportion of Subjects With Sustained Response From Day 2 Through Day 28

    Time frame: Day 2 through Day 28

    Subjects achieving sustained response, defined as a ≥50% reduction from Baseline in MADRS total score, with onset by Day 2 and maintained through the end of the double-blind treatment period.

  7. Proportion of Subjects With Clinical Global Impression of Improvement (CGI-I) Score of 1 or 2 at Scheduled Postbaseline Visits

    Time frame: Up to Day 28

    The CGI-I is a clinician-rated assessment of change in illness relative to Baseline. Scores range from 1 (very much improved) to 7 (very much worse). This outcome evaluates subjects with a score of 1 (very much improved) or 2 (much improved).

Study contacts

Contact information is provided by the study sponsor or research team.

Lori Lykens

CONTACT

[email protected]

+1(609) 250-6917

Sandy Filosi

CONTACT

[email protected]

+1(609) 250-6920

Sponsors and collaborators

Lead sponsor

ACADIA Pharmaceuticals Inc.

Industry

Registry information

Official study title

A Double-Blind, Placebo-Controlled, Parallel Group, Efficacy and Safety Study of ACP-211 Monotherapy in Adults With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment

Acronym: NORLIGHT

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Dec 16, 2025
Registry last updated
Jul 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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