Zelquistinel for Depression

Recruiting at 2 trial locations

Overseen By Kelly Kosko

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Gate Neurosciences, Inc

Must not be taking: Antidepressants, Antipsychotics, Mood stabilizers, others

Disqualifiers: Bipolar, Psychotic disorders, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

1 Power Preferred Clinic 1 of this trial's clinic is considered top 20 on Power

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

164 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new treatment, GATE-251 (also known as Zelquistinel), can reduce symptoms of depression in adults. Participants will take a tablet once a week for six weeks to determine if it improves their depression compared to a placebo (a dummy pill). The trial also monitors any side effects from the treatment. It is suitable for adults diagnosed with major depressive disorder (MDD) who have experienced symptoms for at least three weeks but not longer than 18 months. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any current antidepressants, antipsychotics, mood stabilizers, sedatives, or stimulants at least 14 days before starting the trial. However, you can continue taking certain anxiety medications and sleep aids if you've been on a stable dose for at least 3 months and don't plan to change the dose during the trial.

Is there any evidence suggesting that GATE-251 is likely to be safe for humans?

Research has shown that zelquistinel, the main ingredient in GATE-251, has been tested in animals. These tests found that it produced effects similar to antidepressants after just one dose. While these results are promising, researchers are still gathering information about its safety in humans.

This trial is in an early stage, focusing primarily on assessing the safety of GATE-251 for people. Limited information is available on how well people tolerate it or what side effects might occur. Due to the early-phase nature of the study, some uncertainty remains about its safety in humans.

Prospective participants should note that this stage is crucial for understanding any potential health issues associated with GATE-251. Researchers will closely monitor participants to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Most treatments for depression, like SSRIs and SNRIs, work by altering serotonin and norepinephrine levels in the brain. However, GATE-251 (zelquistinel) is unique because it targets the NMDA receptors, offering a fresh approach to managing depression. Researchers are excited about this treatment because it promises faster relief from symptoms, with its once-a-week oral tablet potentially providing benefits without the daily dosing required by standard medications. This new mechanism of action could be a game-changer for patients who haven't had success with existing therapies.

What evidence suggests that GATE-251 might be an effective treatment for depression?

Research has shown that zelquistinel, also known as GATE-251, might help reduce symptoms of depression. In this trial, participants will receive either GATE-251 or a placebo. Studies suggest that GATE-251 affects certain parts of the brain involved in mood control. This action may lead to quick and lasting improvements in mood. Early results are promising, indicating potential benefits for mental health. As research continues, experts remain hopeful about its potential in treating depression. ^{1 2 3 4 5}

Who Is on the Research Team?

Ronald M Burch, MD, PhD

Principal Investigator

Gate Neurosciences

Are You a Good Fit for This Trial?

Adults aged 18-64 with Major Depressive Disorder, experiencing a depressive episode lasting between 3 weeks to 18 months. They must be moderately ill or worse and show significant distress or impaired functioning. Women must use birth control or be postmenopausal, and all participants need certain scores on depression and anxiety scales.

Inclusion Criteria

Have you been feeling down or depression most of the day nearly every day?

Exclusion Criteria

Have you been diagnosed with schizophrenia?

Have you been diagnosed with Bipolar Disorder?

Do you have any serious heart, liver, or kidney problems that your doctor is treating you for right now

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive either GATE-251 or placebo once a week for 6 weeks

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GATE-251

Trial Overview The trial is testing GATE-251's effectiveness in treating depression compared to a placebo over six weeks. Participants will take one tablet weekly and have their depression severity assessed at each clinic visit during the study period.

How Is the Trial Designed?

Group I: GATE-251 (zelquistinel) Experimental Treatment 1 Intervention

GATE-251 (zelquistinel) will be administered as a single 10 mg oral tablet one time each week for 6 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo tablet identical in appearance to the experimental treatment tablet, administered as as a single oral tablet one time each week for 6 weeks.

Who Is Running the Clinical Trial?

Gate Neurosciences, Inc

Lead Sponsor

Trials

6

Recruited

850+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Published Research Related to This Trial

Dopamine D3 receptors play a crucial role in motivation and reward-related behaviors, and their dysfunction is linked to symptoms of depression, such as anhedonia and loss of motivation.

Antidepressant treatments can reverse the down-regulation of dopamine D3 receptors caused by stress and depression, suggesting that enhancing dopaminergic neurotransmission through these receptors may contribute to the effectiveness of new antidepressant drugs currently in development, like aripiprazole and cariprazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine D(3) receptor as a new pharmacological target for the treatment of depression. Leggio, GM., Salomone, S., Bucolo, C., et al.[2022]

Buspirone, an azapirone anxiolytic, was studied in five placebo-controlled trials with 382 patients suffering from major depression and anxiety, showing significant improvements in both depressive and anxiety symptoms compared to placebo.

Patients with more severe depression symptoms responded better to buspirone, particularly at a commonly effective dose of 40 mg/day, indicating that azapirones may have important antidepressant properties through their action on the 5-HT1A receptor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects of the 5-HT1A partial agonists in depression: a composite analysis of buspirone in the treatment of depression. Robinson, DS., Rickels, K., Feighner, J., et al.[2021]

Gepirone, a serotonin receptor agonist, has been shown to be effective in treating major depression, outperforming placebo in two double-blind studies, with an established dose range of 5-30 mg/day.

In addition to its acute treatment efficacy over 8 weeks, gepirone also provided benefits in continuation therapy over 4 weeks for patients who initially responded well, particularly improving core depression symptoms as measured by the Hamilton Rating Scale.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gepirone in the treatment of major depression. Jenkins, SW., Robinson, DS., Fabre, LF., et al.[2019]

In a phase 3 study involving 481 adults with major depressive disorder, vilazodone (40 mg/day) showed significant improvement in depression symptoms compared to placebo, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS).

Vilazodone was well tolerated, with common side effects including diarrhea and nausea, but it did not significantly affect sexual function or weight compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. Khan, A., Cutler, AJ., Kajdasz, DK., et al.[2022]

Ketamine, an NMDA receptor antagonist, has shown rapid and significant antidepressant effects in treatment-resistant depression (TRD), with an (S)-ketamine nasal spray now approved for use alongside oral antidepressants in the U.S. and Europe.

Despite its effectiveness, challenges such as maintaining response, potential side effects, and abuse risk remain, highlighting the need for further research to develop safer, next-generation rapid-acting antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for depression. Jelen, LA., Stone, JM.[2021]

In a study involving 3,263 patients treated with vortioxetine for major depressive disorder in South Korea, the medication demonstrated a favorable safety profile, with only 17.13% reporting any adverse events, most of which were mild.

Vortioxetine was found to be effective, with significant improvements in depression symptoms observed in 1,918 patients after approximately 24 weeks, as indicated by various clinical and patient-reported measures, showing consistent efficacy across different age groups and sexes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of vortioxetine for major depressive disorder: Real-world evidence from a population-based study in South Korea. Moon, SW., Kim, JW., Kim, DH., et al.[2023]

Zuranolone (30mg) showed significant benefits in treating major depressive disorder (MDD), with a number needed to treat (NNT) of 3-5 for response and remission by Day 15, indicating it is effective compared to placebo and standard antidepressants.

The analysis also revealed a negative number needed to harm (NNH), suggesting that zuranolone is associated with a lower risk of treatment discontinuation compared to SSRIs and SNRIs, highlighting its favorable benefit-to-risk profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Number Needed to Treat and Number Needed to Harm analysis of the zuranolone phase 2 clinical trial results in major depressive disorder. Arnaud, A., Suthoff, E., Stenson, K., et al.[2022]

Zelquistinel, a novel NMDAR allosteric modulator, shows high oral bioavailability and produces rapid and sustained antidepressant-like effects in rodent models by enhancing synaptic plasticity.

The antidepressant effects of zelquistinel are linked to its ability to increase NMDAR function, as evidenced by improved performance in depression models and a favorable safety profile, with no negative impact on motor coordination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor Allosteric Modulator That Exhibits Rapid and Sustained Antidepressant-Like Effects. Burgdorf, JS., Zhang, XL., Stanton, PK., et al.[2023]

In a study of 269 patients with treatment-resistant depression (TRD) using esketamine (ESK) intranasal spray, 61.3% completed the recommended induction phase, indicating good adherence to treatment.

Post-initiation of ESK, there was a trend of reduced mental health-related inpatient and emergency department costs, suggesting potential economic benefits alongside clinical outcomes for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment patterns, healthcare utilization, and costs of patients with treatment-resistant depression initiated on esketamine intranasal spray and covered by US commercial health plans. Joshi, K., Pilon, D., Shah, A., et al.[2023]

A study analyzing 720 cases of esketamine-related neurological adverse events (AEs) from 2019 to 2021 identified 21 safety signals, with sedation being the most concerning (ROR of 204.00), indicating potential long-term safety issues with esketamine.

The severity of neurological AEs was influenced by factors such as esketamine dosage and co-prescription with other medications, highlighting the need for careful monitoring and management of these risks in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological Adverse Events Associated With Esketamine: A Disproportionality Analysis for Signal Detection Leveraging the FDA Adverse Event Reporting System. Guo, H., Wang, B., Yuan, S., et al.[2022]

Edivoxetine, when used as an adjunctive treatment to SSRIs, showed a higher rate of treatment-emergent adverse events (TEAEs) compared to placebo, with 56.8% of patients reporting at least one TEAE, indicating a need for careful monitoring of side effects.

The safety profile of edivoxetine included significant increases in blood pressure and pulse rate, but no clinically significant changes in laboratory measures, suggesting that while it may enhance treatment efficacy, it also carries specific cardiovascular considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of edivoxetine as adjunctive treatment to selective serotonin reuptake inhibitor antidepressants for patients with major depressive disorder. Martinez, JM., Ferguson, MB., Pangallo, BA., et al.[2020]

Intranasal esketamine significantly improved depression scores in patients with major depressive disorder (MDD), including treatment-resistant depression (TRD) and major depression with suicidal ideation (MDSI), starting from 2-4 hours after administration and maintaining effectiveness for up to 28 days, based on a meta-analysis of 8 randomized controlled trials involving 1,488 patients.

Esketamine was associated with a greater resolution of suicidal thoughts in patients with MDSI compared to placebo within the first few hours, although this effect did not persist at later time points. However, it also had a higher incidence of side effects, such as dissociation and increased blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Onset of Intranasal Esketamine in Patients with Treatment Resistant Depression and Major Depression with Suicide Ideation: A Meta-Analysis Wang, SM., Kim, NY., Na, HR., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06547489

Study Details | NCT06547489 | GATE-251 or Placebo for ... The goal of this clinical trial is to learn if GATE-251 works to treat depression in adults. It will also learn about the safety of GATE-251.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9743962/

Zelquistinel Is an Orally Bioavailable Novel NMDA Receptor ... Zelquistinel produces rapid and sustained antidepressant effects by positively modulating the NMDARs, thereby enhancing long-term potentiation of synaptic ...

3. drugtargetreview.com drugtargetreview.com/article/156989/the-future-of-mental-health-treatment-zelquistinel-role/

The future of mental health treatment: Zelquistinel's role Explore the potential of zelquistinel in transforming neuropsychiatric treatment and improving patient outcomes.

4. withpower.com withpower.com/trial/phase-2-depressive-disorder-major-8-2024-76168

Zelquistinel for Depression The goal of this clinical trial is to learn if GATE-251 works to treat depression in adults. It will also learn about the safety of GATE-251.

5. ctv.veeva.com ctv.veeva.com/study/gate-251-or-placebo-for-the-reduction-of-symptoms-of-major-depressive-disorder-with-comorbid-anxiety

GATE-251 or Placebo for the Reduction of Symptoms of Major ... The goal of this clinical trial is to learn if GATE-251 works to treat depression in adults. It will also learn about the safety of GATE-251 ...