Esketamine for Major Depressive Disorder

(SOLEO Trial)

Overseen By Patient Information Page https://www.osmind.org/SOLEO-Study-Patient-Information-Page

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Clexio Biosciences Ltd.

Must be taking: Antidepressants

Must not be taking: Ketamine, PCP, LSD, MDMA

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new medication in people with major depression who haven't improved with at least two other treatments. The drug works by changing brain chemicals to improve mood quickly. It has been approved for adults with difficult-to-treat depression and has been tested in various forms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have an inadequate response to at least 2 antidepressants, suggesting you may continue your current antidepressant.

What data supports the effectiveness of the drug Esketamine for treating major depressive disorder?

Research shows that Esketamine, when combined with standard antidepressants, can help patients with major depressive disorder who haven't responded to other treatments. Studies found that it can lead to higher remission rates and quicker improvement in symptoms compared to a placebo. ^{1 2 3 4 5}

Is esketamine safe for treating major depressive disorder?

Esketamine has been associated with some neurological side effects like sedation, dizziness, and changes in taste, and there are concerns about its long-term safety. Clinical trials have shown an increased risk of side effects such as nausea and dissociation (feeling disconnected from reality) compared to a placebo. However, the quality of reporting on these side effects in trials has been poor, making it difficult to fully understand the risks. ^{6 7 8 9 10}

How does the drug esketamine differ from other treatments for major depressive disorder?

Esketamine is unique because it works by modulating NMDA receptors involved in glutamatergic neurotransmission, offering a rapid antidepressant effect compared to traditional antidepressants. It is administered intranasally, providing a novel route that can be more convenient and faster-acting for patients who have not responded to other treatments. ^{1 2 11 12 13}

Eligibility Criteria

This trial is for individuals with Major Depressive Disorder (MDD) who haven't had enough improvement from at least two standard antidepressants. Participants must be currently taking an oral antidepressant.

Inclusion Criteria

Have you been experiencing a Major Depressive Episode for at least 12 weeks?

Have you tried at least 2 antidepressant medications without relief?

MADRS score of 24 or higher at Screening as confirmed by an independent SAFER assessor

Exclusion Criteria

Have you been diagnosed with Bipolar Disorder or Schizophrenia or Schizoaffective Disorder?

Do you struggle with dementia, amnesia, delirium, or any other significant cognitive disorder?

History or current diagnosis of bipolar disorder, schizophrenia, schizoaffective disorder, or other schizophrenia spectrum disorders

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or CLE-100 (oral esketamine) once daily in addition to their current oral antidepressant monotherapy

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Extension

Participants who complete the Double-Blind Treatment Period and meet eligibility criteria may continue with CLE-100 for an additional 6 months

6 months

Treatment Details

Interventions

• CLE-100

Trial Overview The study tests CLE-100, a form of oral esketamine, as an add-on to existing antidepressant treatment versus a placebo. It's a Phase 2 trial where participants are randomly assigned to either the test drug or placebo without knowing which one they receive.

Participant Groups

Group I: CLE-100 Experimental Treatment 1 Intervention

1 oral tablet of CLE-100 once daily (in addition to current anti-depressant drug) for 4 weeks

Group II: Placebo Placebo Group 1 Intervention

1 oral tablet of Placebo once daily (in addition to current anti-depressant drug) for 4 weeks.

Who Is Running the Clinical Trial?

Clexio Biosciences Ltd.

Lead Sponsor

Trials

3

Recruited

280+

Findings from Research

Intranasal esketamine, when combined with SSRIs or SNRIs, has been shown to be more effective than using these antidepressants alone for treating resistant major depressive disorder, based on a systematic review of four high-quality randomized controlled trials.

Esketamine is recommended as a second-line treatment option for adults aged 18 to 74 who have not responded to at least two previous antidepressant treatments, but caution is advised in its use, particularly regarding patients with suicidal ideation or psychotic depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of esketamine in resistant major depressive disorder: A systematic review of the literature]. Mungo, A., Hein, M.[2022]

Esketamine offers a new treatment option for patients with major depressive disorder (MDD) who have not responded adequately to two or more antidepressant therapies, addressing a significant gap in care for those with moderate to severe depression.

An expert panel of 11 professionals has developed practical recommendations for establishing esketamine clinics in Australia, focusing on patient selection, administration, adverse event management, and long-term follow-up to ensure effective treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishing an esketamine clinic in Australia: Practical recommendations and clinical guidance from an expert panel. Thornton, NLR., Black, W., Bognar, A., et al.[2023]

In a study of 362 patients with major depressive disorder and active suicidal ideation, those receiving esketamine nasal spray plus standard care showed a significantly higher response rate (63.9% vs 48.0%) compared to those receiving placebo at 4 weeks, indicating its efficacy even for patients who did not respond initially.

Patients who did not show improvement within the first week still had a good chance of achieving response and remission by the end of the 4-week treatment, suggesting that esketamine can be beneficial for those who may not respond quickly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment response to esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior without evidence of early response: a pooled post hoc analysis of ASPIRE. Turkoz, I., Lopena, O., Salvadore, G., et al.[2022]

Esketamine combined with an antidepressant significantly improves depression symptoms in treatment-resistant patients, as shown by a meta-analysis of 701 patients, with notable reductions in MADRS and SDS scores.

The combination treatment also leads to higher response and remission rates compared to placebo, indicating its efficacy, although some minor adverse reactions may occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Esketamine Combined with Antidepressants for Treatment-Resistant Depression: A Meta-Analysis. Liu, P., Zhang, SS., Liang, Y., et al.[2022]

Esketamine (ESK) nasal spray combined with standard care significantly reduced the time to remission in adults with major depressive disorder (MDD) and acute suicidal ideation, with median times of 15 days for ESK compared to 23 days for placebo.

Patients receiving ESK also had a higher proportion achieving remission by Day 25 (65.2% vs. 55.5%) and spent more days in remission (27.1% vs. 8.3%), highlighting its efficacy in treating severe depression with suicidality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality. Fu, DJ., Zhang, Q., Shi, L., 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]

A review of 10 clinical trials on esketamine for resistant depression found that 90% of the trials had low-quality reporting of adverse events (AEs), indicating significant gaps in safety data.

The study revealed that 41.5% of serious AEs and 39% of non-serious AEs were not reported in published articles, particularly psychiatric and cardiovascular events, suggesting that the assessment of esketamine's risk-benefit balance may be inaccurate due to incomplete harm reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of harms in clinical trials of esketamine in depression: a systematic review. Taillefer de Laportalière, T., Jullien, A., Yrondi, A., et al.[2023]

Esketamine has been shown to induce antidepressant effects in patients with Major Depression Disorder (MDD), based on a meta-analysis of four randomized controlled trials involving 551 patients.

However, the analysis revealed a significant increase in adverse effects compared to placebo, including nausea, dissociation, dizziness, and sedation, indicating that while esketamine can be effective, it also carries specific risks that need to be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials. Yang, S., Wang, J., Li, X., et al.[2022]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., et al.[2023]

Intranasal esketamine (ESK) has been shown to provide significant and rapid improvement in patients with treatment-resistant depression (TRD) compared to placebo, making it a promising option for those who do not respond to traditional antidepressants.

While esketamine is effective, it can cause common side effects such as dizziness, vertigo, headache, and increased blood pressure, highlighting the need for further long-term studies to fully understand its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Esketamine: a glimmer of hope in treatment-resistant depression. Kaur, U., Pathak, BK., Singh, A., et al.[2021]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

Intranasal esketamine significantly improves response and remission rates in patients with major depressive disorder (MDD) compared to placebo, with effects starting as early as 2 hours and lasting for at least 28 days, based on a meta-analysis of 4 randomized controlled trials involving 708 patients.

While intranasal esketamine shows rapid antidepressant effects, it is associated with a higher rate of discontinuation due to intolerability, indicating a need for further research on its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive intranasal esketamine for major depressive disorder: A systematic review of randomized double-blind controlled-placebo studies. Zheng, W., Cai, DB., Xiang, YQ., et al.[2022]

Ketamine is a rapid-acting antidepressant that can show effects within hours and sustain relief from Major Depressive Disorder (MDD) symptoms for up to 7 days, representing a significant advancement for treatment-resistant depression.

The chapter discusses ketamine's safety and efficacy, including its potential to reduce suicidal thoughts and its interaction with psychotherapy, highlighting its role as a novel therapeutic option for individuals who do not respond to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Major Depressive Disorder. Costi, S.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

[The efficacy of esketamine in resistant major depressive disorder: A systematic review of the literature]. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Establishing an esketamine clinic in Australia: Practical recommendations and clinical guidance from an expert panel. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment response to esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior without evidence of early response: a pooled post hoc analysis of ASPIRE. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Esketamine Combined with Antidepressants for Treatment-Resistant Depression: A Meta-Analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Neurological Adverse Events Associated With Esketamine: A Disproportionality Analysis for Signal Detection Leveraging the FDA Adverse Event Reporting System. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Reporting of harms in clinical trials of esketamine in depression: a systematic review. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Esketamine: a glimmer of hope in treatment-resistant depression. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Adjunctive intranasal esketamine for major depressive disorder: A systematic review of randomized double-blind controlled-placebo studies. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

Ketamine for Major Depressive Disorder. [2023]