Centanafadine for Depression

(JUNIPER Trial)

Recruiting at 56 trial locations

Overseen By Otsuka Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Must be taking: SSRIs

Disqualifiers: Schizophrenia, Bipolar, PTSD, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

336 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trial to assess the efficacy, safety, and tolerability of centanafadine once-daily (QD) extended-release (XR) capsules for the treatment of adult subjects diagnosed with Major Depressive Disorder (MDD). The trial will evaluate the efficacy and safety of centanafadine QD XR capsules as monotherapy or as adjunct to the selective serotonin reuptake inhibitor (SSRI), escitalopram.

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 centanafadine can be used alone or with the SSRI escitalopram, suggesting you might be able to continue certain medications.

Will I have to stop taking my current medications?

The trial allows participants to continue taking the SSRI escitalopram, but it does not specify about other medications. It's best to discuss your current medications with the trial team to see if any changes are needed.

What safety data exists for Centanafadine or related treatments?

The research articles provided do not contain specific safety data for Centanafadine or its related names. However, they discuss the safety and tolerability of other antidepressants, such as SNRIs, which are generally well tolerated with fewer side effects compared to older antidepressants. ^{1 2 3 4 5}

Eligibility Criteria

Adults with Major Depressive Disorder who haven't had enough relief from 1-3 previous depression treatments can join this trial. It's not clear what excludes someone, but typically it would be things like other serious health issues or being on conflicting medications.

Inclusion Criteria

I have tried an antidepressant that didn't work for me.

Exclusion Criteria

Have you had any suicidal thoughts or actions

My blood pressure and diabetes are under control.

History of schizophrenia or bi-polar depression?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive centanafadine QD XR capsules as monotherapy or as adjunct to SSRI for Major Depressive Disorder

6 weeks

Visits at Baseline, Weeks 1, 2, 4, and 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Centanafadine
• Escitalopram
• Placebo

Trial Overview The trial is testing Centanafadine as a standalone treatment or alongside Escitalopram (an SSRI) against a placebo. Participants will be randomly assigned to one of these groups and won't know which they're receiving during the 6-week study.

Participant Groups

Group I: Centanafadine + Placebo Experimental Treatment 2 Interventions

Group II: Centanafadine + Escitalopram Experimental Treatment 2 Interventions

Group III: Escitalopram + Placebo Active Control 2 Interventions

1 escitalopram XR capsule and 2 placebo XR capsules to be taken once daily in the morning.

Group IV: Placebo + Placebo Placebo Group 1 Intervention

3 placebo XR capsules to be taken once daily in the morning.

Who Is Running the Clinical Trial?

Otsuka Pharmaceutical Development & Commercialization, Inc.

Lead Sponsor

Trials

271

Recruited

170,000+

John Kraus

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Medical Officer since 2023

MD, PhD

Tarek Rabah

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Executive Officer since 2022

BS in Biology and BA in Business from the American University of Beirut, MBA from McGill University

Findings from Research

In a phase III study involving 434 patients with major depressive disorder, levomilnacipran ER demonstrated significant efficacy compared to placebo, with notable improvements in depression symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Sheehan Disability Scale (SDS).

While levomilnacipran ER was effective, it also had a higher incidence of adverse events (81.6% in the treatment group vs. 61.8% in placebo), with common side effects including nausea, dizziness, and insomnia, indicating that while it is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder. Sambunaris, A., Bose, A., Gommoll, CP., et al.[2022]

Ketamine, an NMDA antagonist, has shown rapid improvement in depressive symptoms for patients who do not respond to traditional antidepressants, with effects lasting several days after a low-dose infusion.

A pilot study indicated that a higher-dose, 96-hour infusion of ketamine, combined with clonidine to reduce side effects, resulted in about 40% of subjects maintaining a good response for 8 weeks, highlighting the need for further research to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NMDA Antagonists for Treatment-Resistant Depression. Farber, NB.[2019]

In two Phase III studies involving 614 patients with major depressive disorder, TC-5214 (dexmecamylamine) did not show significant antidepressant effects compared to placebo, as measured by the Montgomery Åsberg Depression Rating Scale (MADRS).

While TC-5214 was generally well tolerated, the most common side effects reported were constipation and headache, indicating that while it may not be effective, it does not pose significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant. Vieta, E., Thase, ME., Naber, D., et al.[2022]

Tricyclic antidepressants (TCAs) like clomipramine are still considered highly effective, but selective serotonin reuptake inhibitors (SSRIs) are better tolerated, though their efficacy may be inferior in some cases.

Serotonin and noradrenaline reuptake inhibitors (SNRIs) like milnacipran show promise as they can be more effective than SSRIs at usual doses, offering similar efficacy to TCAs but with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serotonin noradrenaline reuptake inhibitors: Logical evolution of antidepressant development. Montgomery, S.[2014]

Serotonin noradrenaline reuptake inhibitors (SNRIs), including milnacipran, venlafaxine, and duloxetine, are effective in treating major depressive disorder (MDD) with similar potency to tricyclic antidepressants (TCAs) but with fewer side effects.

SNRIs are generally well tolerated and considered safer than TCAs, making them a suitable first-line treatment option for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Serotonin-noradrenaline reuptake inhibitors(SNRIs)]. Ishigooka, J.[2022]

References

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

A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

NMDA Antagonists for Treatment-Resistant Depression. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant. [2022]

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

Serotonin noradrenaline reuptake inhibitors: Logical evolution of antidepressant development. [2014]

5. Japan pubmed.ncbi.nlm.nih.gov

[Serotonin-noradrenaline reuptake inhibitors(SNRIs)]. [2022]