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

August 4, 2026 updated by: ACADIA Pharmaceuticals Inc.

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

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?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

153

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Active, not recruiting
        • University of Alabama at Birmingham
    • California
      • Chino, California, United States, 91710
        • Recruiting
        • Inland Psychiatric Medical Group
      • Glendale, California, United States, 91107
        • Recruiting
        • Behavioral Research Specialists, LLC
      • La Jolla, California, United States, 92037
        • Recruiting
        • Kadima Neuropsychiatry Institute
      • Orange, California, United States, 92866
        • Recruiting
        • PNS Clinical Research LLC dba ATP Clinical Research
    • Colorado
      • Denver, Colorado, United States, 80209
        • Recruiting
        • Mountain View Clinical Research
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Recruiting
        • New Access Research and Medical Services, Inc.
      • Hollywood, Florida, United States, 33021
        • Recruiting
        • The Medici Medical Research
      • Largo, Florida, United States, 33777
        • Active, not recruiting
        • Sandhill Research, LLC/DBA Accel Research Sites
      • Orlando, Florida, United States, 32801
        • Recruiting
        • Clinical Neuroscience Solutions, Inc.
      • Tampa, Florida, United States, 33629
        • Recruiting
        • IPTB Clinical Research
      • West Palm Beach, Florida, United States, 33407
        • Recruiting
        • Neuroscience Research Institute, Inc.
    • Massachusetts
      • Watertown, Massachusetts, United States, 02472
        • Recruiting
        • Adams Clinical, Inc.
      • Worcester, Massachusetts, United States, 01608
        • Recruiting
        • Vitalix Clinical, Inc.
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Recruiting
        • Precise Research Centers
    • Missouri
      • Saint Charles, Missouri, United States, 63304
        • Recruiting
        • St. Charles Psychiatric Associates, Inc. dba Midwest Research Group
    • Nebraska
      • Lincoln, Nebraska, United States, 68526
        • Recruiting
        • Alivation Research, LLC
    • Nevada
      • Las Vegas, Nevada, United States, 89134
        • Recruiting
        • Redbird Research LLC
    • New Jersey
      • Marlton, New Jersey, United States, 08053
        • Active, not recruiting
        • CenExel Hassman Research Institute, LLC
    • New York
      • Brooklyn, New York, United States, 11229
        • Recruiting
        • Integrative Clinical Trials LLC
    • North Carolina
      • Cary, North Carolina, United States, 27511
        • Recruiting
        • Magnolia Clinical Research, LLC
    • Ohio
      • North Canton, Ohio, United States, 44720
        • Recruiting
        • Neuro-Behavioral Clinical Research
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine
      • Houston, Texas, United States, 77081
        • Withdrawn
        • Dynamed Clinical Research LP d/b/a DM Clinical Research
      • Katy, Texas, United States, 77450
        • Recruiting
        • Olympus Clinical Research, LLC
      • The Woodlands, Texas, United States, 77381
        • Recruiting
        • Family Psychiatry of The Woodlands

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ACP-211 600 mg
ACP-211 600 mg, administered orally twice weekly
Drug: ACP-211
ACP-211 monotherapy
Experimental: ACP-211 300 mg
ACP-211 300 mg, administered orally twice weekly
Drug: ACP-211
ACP-211 monotherapy
Placebo Comparator: Placebo
Matching placebo, administered orally twice weekly
Drug: Placebo
Placebo control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and Day 2 (24 hours postdose)
Change From Baseline in MADRS Total Score at Scheduled Postbaseline Visits
Time Frame: Baseline through Day 28
Baseline through Day 28
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.
Baseline through Day 28
Proportion of Subjects in Remission at Scheduled Postbaseline Visits (MADRS ≤10)
Time Frame: Up to Day 28
Up to Day 28
Proportion of Subjects With Response at Scheduled Postbaseline Visits (≥50% Reduction From Baseline in MADRS Total Score)
Time Frame: Up to Day 28
Up to Day 28
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.
Day 2 through Day 28
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).
Up to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ACADIA Pharmaceuticals Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 14, 2025

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

December 9, 2025

First Submitted That Met QC Criteria

December 9, 2025

First Posted (Actual)

December 16, 2025

Study Record Updates

Last Update Posted (Actual)

August 6, 2026

Last Update Submitted That Met QC Criteria

August 4, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACP-211-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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