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

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: Depressive Disorder, Treatment-Resistant; Major Depressive Disorder (MDD)
• Intervention / Treatment: Drug: Placebo; Drug: ACP-211

• Study Type: Interventional
• Enrollment (Estimated): 153
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sandy Filosi; Phone Number: +1(609) 250-6920; Email: sfilosi@ACADIA-Pharm.com
• Study Contact Backup: Name: Lori Lykens; Phone Number: +1(609) 250-6917; Email: lori.lykens@acadia-pharm.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
  • California
    • Chino, California, United States, 91710
      • Recruiting
      • Inland Psychiatric Medical Group
    • 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
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • The Medici Medical Research
    • Largo, Florida, United States, 33777
      • 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
    • Worcester, Massachusetts, United States, 01608
      • Recruiting
      • Vitalix Clinical, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89134
      • Recruiting
      • Redbird Research LLC
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Recruiting
      • CenExel Hassman Research Institute, LLC
  • New York
    • Brooklyn, New York, United States, 11229
      • Recruiting
      • Integrative Clinical Trials LLC
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Recruiting
      • Neuro-Behavioral Clinical Research
  • Texas
    • Houston, Texas, United States, 77081
      • Recruiting
      • Dynamed Clinical Research LP d/b/a DM Clinical Research
    • Katy, Texas, United States, 77450
      • Recruiting
      • Olympus Clinical Research, LLC

Participation Criteria

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)
• Documented non-response to ADT, including ketamine or esketamine
• 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

How is the study designed?

Design Details

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

Number of Arms

3

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 the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Day 28	The MADRS is a clinician-rated tool 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	Time Frame
Change from Baseline in the MADRS total score postdose at 24 hours (Day 2)	Baseline and Day 2

Collaborators and Investigators

• Sponsor: ACADIA Pharmaceuticals Inc.

Study record dates

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): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Ketamine; Randomized Controlled Trial; Major Depressive Disorder (MDD); Antidepressive Agents; Clinical Trial, Phase II; Double-Blind Method; Depressive Disorder, Treatment-Resistant; Psychiatric Status Rating Scales
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
• 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