Zelquistinel in the Treatment of Adults With Major Depres... | NCT03726658

Label	Type	Description	Intervention Names
AGN-241751 3mg	Experimental	AGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B	Drug: AGN-241751
AGN-241751 10mg	Experimental	AGN-241751, oral administration, once per day	Drug: AGN-241751
AGN-241751 25mg	Experimental	AGN-241751, oral administration, once per day in Part A. Twice per day (BID) in Part B	Drug: AGN-241751
Placebo	Placebo Comparator	Placebo, oral administration, once per day in part A. Twice per day (BID) in Part B	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
AGN-241751	Drug	AGN-241751 is supplied in tablet form	AGN-241751 10mg AGN-241751 25mg AGN-241751 3mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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.	Baseline (Day 1) to Day 8

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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
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.

Name	Affiliation	Role
Ronald M Burch, MD PhD	Syndeio Biosciences, Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Alea Research		Phoenix	Arizona	85012	United States
Collaborative Neuroscience Network, LLC

Arm/Group Information

ID	Title	Description
FG000	AGN-241751 3mg Daily	AGN-241751, oral administration, once per day in Part A. AGN-241751: AGN-241751 is supplied in tablet form
FG001	AGN-241751 10mg Daily	AGN-241751, oral administration, once per day in Part A. AGN-241751: AGN-241751 is supplied in tablet form
FG002	AGN-241751 25mg Daily	AGN-241751, oral administration, once per day in Part A. AGN-241751: AGN-241751 is supplied in tablet form
FG003	Placebo Daily	Placebo, oral administration, once per day in part A. Placebo: Placebo is supplied in tablet form
FG004	AGN-241751 3mg Two Times Per Day	AGN-241751, oral administration, BID in Part B. AGN-241751: AGN-241751 is supplied in tablet form
FG005	AGN-241751 25mg Two Times Per Day	AGN-241751, oral administration, BID in Part B. AGN-241751: AGN-241751 is supplied in tablet form
FG006	Placebo 2 Times Per Day	Placebo, oral administration, two times per day in part B. Placebo: Placebo is supplied in tablet form

ID	Title	Description
BG000	AGN-241751 3mg Daily	AGN-241751, oral administration, once per day in Part A. AGN-241751: AGN-241751 is supplied in tablet form
BG001	AGN-241751 10mg Daily	AGN-241751, oral administration, once per day in Part A. AGN-241751: AGN-241751 is supplied in tablet form

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Modified Intent-to-Treat

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Day1) to Day 2

ID	Title	Description
OG000	AGN-241751 3mg Daily	AGN-241751, oral administration, once per day in Part A. AGN-241751: AGN-241751 is supplied in tablet form

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 3, 2019	Mar 1, 2023	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jun 7, 2019	Mar 1, 2023	SAP_001.pdf

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders