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Major Depressive DisorderPhase 1/2AGN-241751NCT03726658

Zelquistinel in the Treatment of Adults With Major Depressive Disorder

A Phase 1/2 study testing AGN-241751 in people with Major Depressive Disorder, run by Syndeio Biosciences, Inc at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the efficacy and safety of AGN-241751 in participants with Major Depressive Disorder Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Major Depressive Disorder
What is being tested?
AGN-241751
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
226 participants
Where
5 sitesUnited States
Study dates
8 Nov 2018to 23 Oct 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent from the participant has been obtained prior to any study-related procedures
  • Meet DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) criteria (American Psychiatric Association, 2013). for MDD (based on confirmation from the modified SCID), with a current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1.
  • Have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening (Visit 1) if a WOCBP (Women of Childbearing Potential).
  • Female participants willing to minimize the risk of becoming pregnancy for the duration of the clinical study and follow-up period. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a WOCBP (Women of Childbearing Potential). OR
  • A WOCBP (Women of Childbearing Potential). who agrees to follow the contraceptive guidance in during the treatment period and for at least 4 to 5 weeks after the last dose of study treatment.
  • Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. A male participant must agree to use contraception during the treatment period and for at least 10 weeks after the last dose of study treatment and refrain from donating sperm during this period.
  • Able, as assessed by the investigator, and willing to follow study instructions and likely to complete all required study visits.

Who cannot join

  • Psychiatric and Treatment-Related Criteria
  • DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1. Comorbid generalized anxiety disorder, social anxiety disorder, or specific phobias are acceptable provided they play a secondary role in the balance of symptoms and are not the primary driver of treatment decisions.
  • Lifetime history of meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition)criteria for:
  • Schizophrenia spectrum or other psychotic disorder
  • Bipolar or related disorder
  • Major neurocognitive disorder
Show all 40Show fewer
  • Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study
  • Dissociative disorder
  • Posttraumatic stress disorder
  • MDD with psychotic features
  • History of meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) criteria for alcohol or substance use disorder (other than nicotine or caffeine) within the 6 months before Screening (Visit 1).
  • History (based on participant report and/or medical records, and investigator judgment) of the following:
  • Inadequate response to ECT, a monoamine oxidase inhibitor, ketamine, or adjunctive treatment with an antipsychotic
  • Treatment with clozapine or any depot antipsychotic
  • ECT, vagus nerve stimulation, transcranial magnetic stimulation, or any experimental central nervous system treatment during the current episode or in the 6 months before Screening (Visit 1) whichever is longer)
  • Tardive dyskinesia, serotonin syndrome, or neuroleptic malignant syndrome
  • Having received:
  • Anticonvulsant/mood stabilizer, within 1 year prior to Screening (Visit 1)
  • Antipsychotic in the current episode, with the exception of quetiapine given for insomnia ≤ 50 mg/day provided it can be safely discontinued prior to Visit 2
  • Combination therapy of more than 2 ADTs in the current episode if given for depression at adequate dose and duration
  • ADT augmentation agent in the current episode
  • Lifetime history of nonresponse to ≥ 2 antidepressants after adequate trials (adequate treatment is defined as at least 6 weeks at an adequate dose(s) based on approved package insert recommendations).
  • Positive result at Screening (Visit 1) from the UDS (Urine Drug Screen) test for any prohibited medication. Exception: Participants with a positive UDS (Urine Drug Screen) at Screening for opiates, cannabinoids, or episodic use of benzodiazepines may be allowed in the study provided:
  • The drug was used for a legitimate medical purpose;
  • The drug can be safely discontinued prior to participation in the study (except for episodic use of benzodiazepines which may be continued); and
  • A repeat UDS is negative for these substances prior to enrollment (except for episodic use of benzodiazepines which may be continued)
  • Part B participants who have regularly been using benzodiazepines (even for legitimate medical purposes) for more than 2 months should not be included in the study if there is doubt that the medication can be safely discontinued during screening.
  • A suicide attempt within the past year
  • Prior participation in any investigational study of AGN-241751
  • Initiation or termination of psychotherapy for depression within the 3 months preceding Screening (Visit 1), or plans to initiate, terminate, or change such therapy during the course of the study. (Support meetings or counseling [eg, marital counseling] are allowed provided they are no more frequent than weekly and do not have treatment of depression as their objective.)
  • Ongoing treatment with phototherapy, or termination of phototherapy within 1 month of Visit 1.
  • Known allergy or sensitivity to the study medication or its components.
  • Hypothyroidism or hyperthyroidism, unless stabilized on appropriate pharmacotherapy with no change in dosage for at least 1 month before Screening (Visit 1)
  • History of seizure disorder, stroke, significant head injury, tumor of the central nervous system, or any other condition that predisposes to seizure.
  • Known HIV infection
  • Part B: Previously diagnosed hearing loss; current hearing aid users (within the last 6 months), or history of gross hearing loss, such as conductive hearing loss, congenital hearing loss, sudden hearing loss, hearing loss due to recent noise or occupational exposure.
  • Current enrollment in an investigational drug or device study or participation in such a study within 6 months of entry into this study (or within 3 months of entry into this study (Part B).
  • Part B: Prior participation in any investigational study of AGN-241751, rapastinel, ketamine, or esketamine. Part B participants should not have participated in Part A at any time, and Part A participants should not have participated in Part B at any time (ie, Part A is not a contingent step to participate in Part B).
  • Employee, or immediate relative of an employee, of the sponsor, any of its affiliates or partners, or the study center
  • Inability to speak, read, and understand the English language sufficiently to understand the nature of the study, to provide written informed consent, or to allow the completion of all study assessments.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Atlanta Center for Medical Research

    Atlanta, Georgia, 30331

  • Northwest Clinical Research Center

    Bellevue, Washington, 98007

  • Hassman Research Institute

    Berlin, New Jersey, 08809

  • Collaborative Neuroscience Network, LLC

    Garden Grove, California, 92845

  • Alea Research

    Phoenix, Arizona, 85012

Other trials in United States

About this study

Official title: A Two-Part, Double-Blind, Placebo-Controlled, Single- and Multiple-Dose (Part A) or Twice Daily Dose (Part B) Study of AGN-241751 in Adult Participants With Major Depressive Disorder

The purpose of this study is to evaluate the efficacy and safety of AGN-241751 in participants with Major Depressive Disorder

Being tested
AGN-241751, Placebo
Medical subject headings
Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AGN-241751Drug

    AGN-241751 is supplied in tablet form

  • PlaceboDrug

    Placebo is supplied in tablet form

Study groups in NCT03726658
Study groupRoleWhat they receive
AGN-241751 3mgExperimentalAGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B
Receives: Drug: AGN-241751
AGN-241751 10mgExperimentalAGN-241751, oral administration, once per day
Receives: Drug: AGN-241751
AGN-241751 25mgExperimentalAGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B
Receives: Drug: AGN-241751
PlaceboPlacebo comparatorPlacebo, oral administration, once per day in part A. Twice per day (BID) in Part B
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Change in MADRS Score at 1 Day the Initial Dose of AGN-241751 Reported as Change From Baseline in Treated Group Compared With Change From Baseline in Placebo Group

    Efficacy will be measured by improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. The MADRS score ranges from 0 to 60 with a higher score indicating greater depression. A negative change score indicates improvement. Results are reported as change from baseline in treated group compared to change from baseline in placebo, reported as least squares difference and (standard error) calculated from a mixed model-repeated measures analysis

    Measured: Baseline (Day1) to Day 2

  2. Part B: Change From Baseline in MADRS Score at Day 8 Post the Initial Dose of AGN-241751 (i.e. 1 Day After the Seventh Daily Dose)

    Efficacy was measured by improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. The MADRS score ranges from 0 to 60 with a higher score indicating greater depression. A negative change score indicates improvement.

    Measured: Baseline (Day 1) to Day 8

Secondary outcomes (2)
  1. Part A: Change From Baseline in MADRS Score on Day 9 and Day 15 of AGN-241751 Once Daily and at Day 22 (7 Days After Completion of AGN-241751 Dosing) Compared With Change in Placebo

    Efficacy was measured by improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. The MADRS score ranges from 0 to 60 with a higher score indicating greater depression. A negative change score indicates improvement.

    Measured: Baseline (Day 1) to Day 22

  2. Part B: Change From Baseline in MADRS Score on Day 11, Day 14, and Day 18 of AGN-241751 Administered Two Times Daily and on Day 21 (7 Days After Completion of Dosing) in Treated Group Compared to Change From Baseline in Placebo Group

    Efficacy was measured by improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. The MADRS score ranges from 0 to 60 with a higher score indicating greater depression. A negative change score indicates improvement. Results are reported as change from baseline in treated group compared to change from baseline in placebo, reported as least squares difference and (standard error) calculated from a mixed model-repeated measures analysis

    Measured: Baseline (Day 1) to Day 21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2018
  2. Study start8 Nov 2018
  3. Primary completion23 Oct 2019
  4. Study completion23 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
226 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03726658
Sponsor's protocol ID
3125-104-002
Acronym
AGN-241751
Status last verified
Jul 2023
First submitted
30 Oct 2018
Last updated
7 Apr 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AGN-241751 in people with Major Depressive Disorder, run by Syndeio Biosciences, Inc at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Change in MADRS Score at 1 Day the Initial Dose of AGN-241751 Reported as Change From Baseline in Treated Group Compared With Change From Baseline in Placebo Group (time frame: Baseline (Day1) to Day 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.

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