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Enhancer of Synaptic Glutamate Release

HNK for Treatment-Resistant Depression

Phase 2

Recruiting

Led By Carlos A Zarate, M.D.

Research Sponsored by National Institute of Mental Health (NIMH)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age between 18 to 70 years.

Fulfill DSM-IV or DSM-5 criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Must be experiencing a current major depressive episode lasting at least two weeks.

Must not have

Previous antidepressant non-response to ketamine or esketamine (full course).

Serious, unstable medical illnesses including but not limited to hepatic diseases, cardiovascular disease, renal/urologic conditions, endocrinologic disorders, or neurologic diseases.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, 230 min post-drug, and days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per test session.

Summary

This trial aims to test a new drug called (2R,6R)-hydroxynorketamine (HNK) for treating major depressive disorder (MDD). Participants with MDD will

Who is the study for?

This trial is for adults aged 18 to 70 with Major Depressive Disorder (MDD) who haven't responded well to standard treatments. They must have completed a screening assessment and be able to stop their current MDD medications for the duration of the study.

What is being tested?

(2R,6R)-hydroxynorketamine (HNK), a potential fast-acting antidepressant, is being tested against a placebo in people with treatment-resistant depression. Participants will receive infusions over two weeks, take no drugs for another few weeks, then get another set of infusions.

What are the potential side effects?

Possible side effects may include reactions at the infusion site, changes in mood or behavior, alterations in heart function or blood chemistry. Since HNK affects neurotransmitters involved in mood regulation, there might also be risks of seizures or other neurological symptoms.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 70 years old.

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I have been diagnosed with major depression without psychosis, lasting at least two weeks.

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My depression is severe, but my mania is not.

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I have depression that didn't improve after trying at least one antidepressant.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I did not respond to a full course of ketamine or esketamine for depression.

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I do not have any serious, unstable illnesses like heart, liver, kidney diseases, or diabetes.

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I am not currently undergoing any structured psychotherapy.

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I have had a head injury that made me unconscious for more than five minutes.

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My thyroid condition is not stable.

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I have had seizures with no known cause.

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My weight is over 119 kg.

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I currently have or am suspected to have COVID-19.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, 230 min post-drug, and days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per test session.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, 230 min post-drug, and days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per test session.

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, 230 min post-drug, and days 1, 2, 3, 4, 7, 8, 10, 11, and 12, per test session. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change from baseline on Montgomery-Asberg Depression Rating Scale total scores

Change from baseline on item 10 (suicidality) of the Montgomery-Asberg Depression Rating Scale and total score on the Columbia Suicide Severity Rating Scale and the Scale for Suicide Ideation.

Change from baseline on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Affect Schedule, Snaith-Hamilton Pleasure Scale, Temporal Experience of Pleasure Scale, and cognitive tasks.

+3 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: 2Experimental Treatment2 Interventions

Individuals in Arm 2 will receive double-blinded placebo infusions four times over two weeks during Test Session 2 and double-blinded (2R,6R)-HNK infusions four times over two weeks during Test Session 1. The starting dose will be 0.25 mg/kg and the treatment target for all participants will be 2.0 mg/kg. If response criteria is not met by the morning of the next infusion, the dose may be increased. Doses will be decreased if tolerability issues arise.

Group II: 1Experimental Treatment2 Interventions

Individuals in Arm 1 will receive double-blinded (2R,6R)-HNK infusions four times over two weeks during Test Session 1 and daily double-blinded placebo infusions four times over two weeks during Test Session 2. The starting dose will be 0.25 mg/kg and the treatment target for all participants will be 2.0 mg/kg. If response criteria is not met by the morning of the next infusion, the dose may be increased. Doses will be decreased if tolerability issues arise.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

0 / 12Eligibility criteria met