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.
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
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
- Conditions
- 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 group | Role | What they receive |
|---|---|---|
| AGN-241751 3mg | Experimental | AGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B Receives: Drug: AGN-241751 |
| AGN-241751 10mg | Experimental | AGN-241751, oral administration, once per day Receives: Drug: AGN-241751 |
| AGN-241751 25mg | Experimental | AGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B Receives: Drug: AGN-241751 |
| Placebo | Placebo comparator | Placebo, 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.
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
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)
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
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.
- First posted31 Oct 2018
- Study start8 Nov 2018
- Primary completion23 Oct 2019
- Study completion23 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Syndeio Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ronald M Burch, MD PhD, Study director, Syndeio Biosciences, Inc
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
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03726658
- Acronym / sponsor ID
- AGN-241751 / 3125-104-002
- Conditions
- Major Depressive Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- Syndeio Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2018 (actual)
- Primary completion
- 23 Oct 2019 (actual)
- Study completion
- 23 Oct 2019 (actual)
- First posted
- 31 Oct 2018 (actual)
- Results
- Posted 7 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of AGN-241751 in participants with Major Depressive Disorder
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| AGN-241751 3mg | Experimental | Drug: AGN-241751AGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B |
| AGN-241751 10mg | Experimental | Drug: AGN-241751AGN-241751, oral administration, once per day |
| AGN-241751 25mg | Experimental | Drug: AGN-241751AGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, oral administration, once per day in part A. Twice per day (BID) in Part B |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (40 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AGN-241751AGN-241751 is supplied in tablet form | Drug | AGN-241751 10mg, AGN-241751 25mg, AGN-241751 3mg |
| PlaceboPlacebo is supplied in tablet form | Drug | Placebo |
Primary outcome
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
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
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)
Time frame: Baseline (Day 1) to Day 8
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.
2 secondary outcomes
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
Time frame: Baseline (Day 1) to Day 22
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
Time frame: Baseline (Day 1) to Day 21
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald M Burch, MD PhD study director
Syndeio Biosciences, Inc
5 sites in 1 country: see every site and its status.
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.