Esketamine for Major Depressive Disorder
(SOLEO Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
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?
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.678910
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.12111213
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
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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
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Trial 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 (NMDA Receptor Antagonist)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Placebo Group
Group I: CLE-100Experimental Treatment1 Intervention
1 oral tablet of CLE-100 once daily (in addition to current anti-depressant drug) for 4 weeks
Group II: PlaceboPlacebo Group1 Intervention
1 oral tablet of Placebo once daily (in addition to current anti-depressant drug) for 4 weeks.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sunwise Clinical Research, LLC.Walnut Creek, CA
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Who Is Running the Clinical Trial?
Clexio Biosciences Ltd.Lead Sponsor
References
[The efficacy of esketamine in resistant major depressive disorder: A systematic review of the literature]. [2022]Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment.
Establishing an esketamine clinic in Australia: Practical recommendations and clinical guidance from an expert panel. [2023]Major depressive disorder (MDD) can have severe impacts on function and quality of life. Up to one third of patients will have an inadequate response to their first line of treatment, with subsequent lines of therapy associated with lower remission rates and higher relapse rates. Recently esketamine has become available for Australian patients, and this agent provides an additional treatment option for those with MDD who have had an inadequate response to two or more antidepressant therapies during the current moderate to severe depressive episode. This paper provides an expert panel's practical recommendations and clinical guidance for establishing esketamine clinics in Australia.
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]To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response.
Efficacy and Safety of Esketamine Combined with Antidepressants for Treatment-Resistant Depression: A Meta-Analysis. [2022]To evaluate the efficacy and safety of esketamine + antidepressant in treatment-resistant depression.
Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality. [2023]Esketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission.
Neurological Adverse Events Associated With Esketamine: A Disproportionality Analysis for Signal Detection Leveraging the FDA Adverse Event Reporting System. [2022]Esketamine was approved for the treatment of treatment-resistant depression in 2019. After the approval of esketamine, numerous concerns have been raised regarding its long-term safety and tolerability. A previous systematic pharmacovigilance study on esketamine-related adverse events (AEs) was published in 2020; however, it has not been updated 2 years later. The primary aim of this study was to detect and characterize neurological safety signals of esketamine to partially update the knowledge in this field using the FDA pharmacovigilance database. Reporting odds ratio (ROR) was calculated for esketamine-related neurological AEs from 2019 to 2021 with a signal considered when the lower limit of the 95% confidence interval (CI) of ROR (ROR025) exceeded one. Severe and non-severe cases were compared using an independent samples t-test or chi-squared (χ2) test, and a rating scale was used to prioritize the signals. The database contained 720 cases of esketamine-associated neurological AEs, with 21 signals detected, ranging from a ROR025 of 1.05 (disturbance in attention) to 204.00 (sedation). 16 latest neurological AEs emerged in the second year of marketing approval of esketamine, with eight signals detected. The associations between esketamine and nervous system disorders persisted when stratifying by sex, age, and reporter type, whereas the spectrum of neurological AEs differed in stratification regimens. Esketamine dosage, antidepressant polypharmacy, or co-prescription with benzodiazepines affected AEs severity (t = 2.41, p = 0.017; χ2 = 6.75, p = 0.009; and χ2 = 4.10, p = 0.043; respectively), while age and sex did not (p = 0.053 and p = 0.397, respectively). Three signals were categorized as moderate clinical priority [i.e., sedation, dizziness, and dysgeusia (priority points 7, 5, and 5, respectively)], showing the same early failure type profiles. Notably, seven detected disproportionality signals were not previously detected in clinical trials. Although the majority of results were in line with those obtained in the previous study, there were discrepancies in the spectrum of neurological AEs and the effects of several risk factors on AEs severity among the two studies that should be recognized and managed early in clinical treatments.
Reporting of harms in clinical trials of esketamine in depression: a systematic review. [2023]While previous systematic reviews of trials evaluating conventional antidepressants highlighted inadequacies and inconsistencies in adverse event (AE) reporting, no evaluation is available on esketamine in resistant depression. The objective of this review was to assess quality of reporting AEs in all published clinical trials studying esketamine. It also aimed to compare the proportions of AEs reported in journal articles to those recorded in the ClinicalTrial.gov Registers. Clinical trials evaluating the efficacy and safety of esketamine in depression were searched using Medline and ClinicalTrials.gov. The quality of reporting harms was assessed using a 21-item checklist from the CONSORT Extension of Harms (1 point by item). The total quality score was graded into four categories: high (17-21), moderate (12-16), low (7-11) and very low (0-6). Ten clinical trials were included in the analysis. Nine trials were classified as 'low quality' with regard to safety, one trial was classified as 'moderate quality'. Compared to AEs recorded in ClinicalTrials.gov, we found that 41.5% of serious AEs and 39% of non-serious AEs were not reported in the published articles. Among them, the majority were psychiatric events but also cardiovascular events and 94% concerned patients from esketamine groups. Quality of AEs reporting in published clinical trials of esketamine was poor and harms were reported less frequently in journal publications than in ClinicalTrial.gov Registers. The study suggests that an assessment of the benefits/risks balance of esketamine based on the results reported in trial publications is flawed due to the poor accuracy and completeness of harm data.
Adverse Effects of Esketamine for the Treatment of Major Depression Disorder: Findings from Randomized Controlled Trials. [2022]Esketamine is a promising drug which can induce antidepressant effects in Major Depression Disorder (MDD). Several randomized controlled trials (RCTs) have been implemented to assess the efficacy and safety of esketamine for the treatment of MDD. Therefore, we carried out a meta-analysis to assess adverse effect profiles of esketamine for the treatment of MDD. We searched RCTs which were implemented from January 2010 to June 2020 by searching PubMed, Embase and Cochrane Library databases. Finally, four RCTs with 551 patients were included in our study. We pooled 551 patients from 4 RCTs. Compared with placebo, an increased risk of adverse effects was observed in our analysis. After using esketamine, the risk of nausea (RR = 2.34, 95% CI, 1.04 to 5.25, P = 0.04), dissociation (RR = 4.54, 95% CI, 2.36 to 8.73, P
The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]On a background of the rapidly expanding clinical use of ketamine and esketamine for treatment of depression and other conditions, we examined safety monitoring, seeking to identify knowledge gaps relevant to clinical practice.
Esketamine: a glimmer of hope in treatment-resistant depression. [2021]The motive of this article is to review the pharmacological and clinical aspects of esketamine (ESK), an NMDA-receptor antagonist approved recently by the FDA for treatment-resistant depression (TRD). PubMed/Medline database was searched using keywords 'esketamine' and 'depression', 'S-ketamine' and 'depression', and 'NMDA antagonist' and 'depression'. Individual trials were searched from ClinicalTrials.gov. We included English-language articles evaluating pharmacokinetics and pharmacodynamics of intranasal (IN) esketamine, along with clinical trial data related to its efficacy and safety in patients diagnosed with TRD. Compared to placebo, IN esketamine causes significant and rapid improvement in depression. Dizziness, vertigo, headache, increase in blood pressure are some of its common adverse effects. With the growing number of patients of TRD, additional effective and safe treatment is the need of the hour. Esketamine appears to be an effective therapy when combined with oral antidepressants in patients with TRD. It is of special value due to the rapid onset of its action. Long-term clinical studies are, however, needed to ascertain its safety profile.
Subcutaneous Ketamine in Depression: A Systematic Review. [2021]Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability. Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool. Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5-1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects. Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted. Systematic Review Registration: CRD42019137434.
Adjunctive intranasal esketamine for major depressive disorder: A systematic review of randomized double-blind controlled-placebo studies. [2022]This is a meta-analysis of randomized double-blind controlled-placebo trials (RCTs) examining the effectiveness, tolerability, and safety of intranasal esketamine in treating major depressive disorder (MDD).
Ketamine for Major Depressive Disorder. [2023]Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Conventional antidepressant treatment is characterised by a significant time to onset of therapeutic action (approximately 2 weeks) and fails to achieve a stable remission of symptoms in one-third of subjects with MDD. In the last 20 years the discovery of antidepressant effects of the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine as a rapid acting (within hours) and sustained (up to 7 days) antidepressant has represented a major paradigm shift in the field.The present chapter reviews the pharmacology, safety, and efficacy of ketamine as a novel therapeutic agent for MDD and specifically for subjects who did not respond to conventional antidepressant (treatment resistant depression). The impact of ketamine on suicidal ideation, the availability of brain biomarkers of ketamine treatment response and the association of ketamine and psychotherapy are considered.