CTC-501 for Depression

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chase Therapeutics Corporation

Must not be taking: Pramipexole, Ondansetron, MAOI, others

Disqualifiers: Pregnancy, Renal dysfunction, Substance abuse, others

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

Compensation: Varies

Number of Visits: 10

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently on antidepressants, you may need to stop taking them and go through a washout period (time without taking certain medications) before joining the trial. Some antidepressants, like fluoxetine, may require a longer washout period of more than 2 weeks.

What data supports the effectiveness of the drug CTC-501 for depression?

The research mentions that atypical antipsychotics like aripiprazole, which is similar to CTC-501, have been effective as an add-on treatment for depression, improving symptoms significantly in patients who did not respond well to standard antidepressants. ^{1 2 3 4 5}

What safety data exists for CTC-501 (esketamine) in humans?

Esketamine has been studied for treatment-resistant depression, but safety data reporting is often incomplete. Common side effects include dissociation, vertigo, and dizziness, with some reports of serious psychiatric and cardiovascular events. Careful monitoring is recommended due to potential risks, including rare but severe events like apnea. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial tests pramipexole and ondansetron in patients with major depressive disorder. Pramipexole aims to improve mood by affecting brain chemicals, and ondansetron helps prevent nausea. Pramipexole has been tested in various studies for its efficacy in treating major depression, while ondansetron is being explored for its potential benefits in combination with other treatments. The study compares the treatment over a few months.

Research Team

Mark Leibowitz, MD

Principal Investigator

Collaborative Neuroscience Network

Eligibility Criteria

This study is for men and women aged 18-65 with major depressive disorder (MDD), who score above a certain level on the HAM-D depression scale. Participants must not be on antidepressants or agree to stop them before starting the trial, and can't start new psychotherapies during the trial. Pregnant or breastfeeding women, those with significant liver or kidney issues, drug abuse history, serious suicidal risk, or certain other health conditions are excluded.

Inclusion Criteria

I have been diagnosed with major depressive disorder.

I have been diagnosed with major depression without psychosis.

I agree not to start new mental health therapies during the trial, but can continue if already started 3+ months ago.

Exclusion Criteria

My kidney and liver functions are within specific limits.

Lifetime history of certain mental health disorders

History of serious suicidal attempt or tendencies

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Titration

Participants receive pramipexole titrated up to the first intolerable dose or maximum allowed dose

1 week

Daily visits (in-person) until FID or Day 8

Maintenance

Participants continue treatment with pramipexole at maximum tolerated dose or placebo for 8 weeks

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• CTC-501

Trial Overview The clinical trial is testing CTC-501 in patients with MDD. It's a Phase 2a study where participants will either receive this experimental medication or a placebo without knowing which one they're getting (single-blind). The goal is to see if CTC-501 helps improve symptoms of depression compared to no active treatment.

Participant Groups

Group I: treatment Experimental Treatment 1 Intervention

CTC-501 (pramipexole IR, given with ondansetron) given orally twice daily

Group II: placebo Placebo Group 1 Intervention

generic placebo tablets given orally twice daily

Who Is Running the Clinical Trial?

Chase Therapeutics Corporation

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

In two large trials involving adults with major depressive disorder who did not respond adequately to standard antidepressants, adjunctive treatment with aripiprazole (2-20 mg/day) significantly improved depression scores compared to placebo, starting from 1-2 weeks into treatment.

Aripiprazole was generally well tolerated, with most side effects being mild to moderate, and it also led to higher rates of response and remission compared to placebo, indicating its efficacy as an adjunctive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole: in major depressive disorder. Weber, J., Lyseng-Williamson, KA., Scott, LJ.[2021]

The REMIT tool, a brief 5-item questionnaire, has been validated as an effective measure for assessing and predicting improvement in depression among 294 primary care patients, showing strong correlations with mental health metrics.

With a minimally important difference (MID) of about 2 points, REMIT was found to be as effective, if not better, than the PHQ-9 in predicting depression improvement over a 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing depression improvement with the remission evaluation and mood inventory tool (REMIT). Bushey, MA., Kroenke, K., Baye, F., et al.[2020]

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]

In a study involving 97 participants with treatment-resistant depression, ketamine infusions showed a 67% response rate, indicating significant antidepressant effects.

The treatment was found to be safe and well-tolerated, with only a 3.1% attrition rate and no cases of persistent adverse effects, although some participants experienced temporary side effects like drowsiness and dissociation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine safety and tolerability in clinical trials for treatment-resistant depression. Wan, LB., Levitch, CF., Perez, AM., et al.[2022]

Esketamine nasal spray combined with an oral antidepressant significantly improves treatment outcomes for patients with treatment-resistant depression, with 5-21 more patients achieving remission and 14-17 more responding compared to those on a placebo during induction therapy.

In maintenance therapy, esketamine reduces the risk of relapse by 19-32 patients, while the incidence of serious adverse events remains low, indicating a favorable benefit-risk profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment-Resistant Depression. Katz, EG., Hough, D., Doherty, T., et al.[2021]

Ketamine shows promise as a treatment for treatment-resistant depression (TRD), but its use can lead to common adverse events, which are usually temporary.

A case of apnea during a slow sub-anesthetic infusion of ketamine highlights a rare but serious potential side effect, emphasizing the need for careful monitoring and management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. Gómez-Revuelta, M., Fernández-Rodríguez, M., Boada-Antón, L., et al.[2021]

References

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

Aripiprazole: in major depressive disorder. [2021]

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

What are the comparative benefits and harms of augmentation treatments in major depression? [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacogenomics-Guided Pharmacotherapy in Patients with Major Depressive Disorder or Bipolar Disorder Affected by Treatment-Resistant Depressive Episodes: A Long-Term Follow-Up Study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study. [2020]

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

Assessing depression improvement with the remission evaluation and mood inventory tool (REMIT). [2020]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Ketamine safety and tolerability in clinical trials for treatment-resistant depression. [2022]

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

Benefit-Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment-Resistant Depression. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. [2021]