Centanafadine for Depression

(JUNIPER Trial)

No longer recruiting at 65 trial locations

Overseen By Otsuka Contact Center 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate a new treatment option, centanafadine, for individuals with Major Depressive Disorder (MDD). Researchers seek to determine the effectiveness and safety of centanafadine when used alone or with the common antidepressant, escitalopram. Those diagnosed with MDD, currently experiencing a depressive episode, and who have not responded well to 1 to 3 antidepressants may be suitable candidates. The trial includes different groups: some receive centanafadine, some escitalopram, and others a placebo (inactive substance) for comparison. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier research found centanafadine to be safe for long-term use in adults with ADHD (attention-deficit/hyperactivity disorder). Participants tolerated the treatment well, and no major safety issues emerged. Another study with adults also confirmed centanafadine's safety over an extended period.

Although centanafadine is being tested for depression in this trial, the safety results from ADHD studies are promising. However, as this is a phase 2 trial, it is important to remember that centanafadine is still under evaluation specifically for depression. This phase focuses on understanding treatment tolerance and any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about centanafadine for depression because it offers a unique approach compared to standard treatments like SSRIs, SNRIs, and atypical antidepressants. Centanafadine works by inhibiting the reuptake of norepinephrine, dopamine, and serotonin, which may lead to a more balanced neurotransmitter activity. This multi-mechanism approach could potentially offer faster relief of symptoms and a broader range of effectiveness for patients who don't respond well to current options. Additionally, combining centanafadine with escitalopram might enhance efficacy, providing a promising new avenue for those with treatment-resistant depression.

What evidence suggests that this trial's treatments could be effective for Major Depressive Disorder?

Research has shown that centanafadine may help treat symptoms of attention-deficit hyperactivity disorder (ADHD) in both children and adults. Earlier studies found that doses of 200 mg and 400 mg per day effectively improved symptoms. Although primarily studied for ADHD, centanafadine is thought to influence mood, which might aid in treating depression. This trial investigates whether centanafadine alone or combined with escitalopram, a common antidepressant, can improve treatment for major depressive disorder (MDD). While direct evidence for its effect on depression is still being gathered, its potential mood-related benefits make it worth studying for MDD. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05536414

NCT05536414 | Trial of Centanafadine Efficacy and Safety ... The trial will evaluate the efficacy and safety of centanafadine QD XR capsules as monotherapy or as adjunct to the selective serotonin reuptake inhibitor ( ...

2. trials.otsuka-us.com trials.otsuka-us.com/trials/405-201-00062

Trial of Centanafadine Efficacy and Safety as Monotherapy ... 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) ...

3. publications.aap.org publications.aap.org/pediatricsopenscience/article/1/3/1/202430/Efficacy-and-Safety-of-Centanafadine-for-ADHD

Efficacy and Safety of Centanafadine for ADHD Treatment ... Once-daily doses of CTN resulting in plasma levels equivalent to the 400-mg daily adult dose improved ADHD symptoms in children aged 6 to 12 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9426730/

Efficacy, Safety, and Tolerability of Centanafadine ... These are the first large-scale studies to demonstrate the efficacy and safety profiles of 200 mg/d and 400 mg/d centanafadine in adults with ADHD.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07086313?term=rare+disease

A Trial to Evaluate the Efficacy and Safety of EB-1020 in ... The purpose of this study is to evaluate the efficacy and examine the safety of two doses of EB-1020 QD XR capsule administered once daily ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12379780/

52-Week Open-Label Safety and Tolerability Study of ... Results from this trial demonstrate that CTN SR 400 mg is safe and effective for long-term treatment of adults with ADHD. Key Words: ADHD ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05428033

Study Details | NCT05428033 | A Trial of Centanafadine ... This trial will be conducted to evaluate the efficacy of centanafadine QD XR versus placebo in the treatment of child subjects (4 to 12 years, inclusive) with ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7292254/

Safety and Efficacy of Centanafadine Sustained-Release in ... Two phase 2 studies evaluated the efficacy and tolerability of centanafadine sustained-release (SR) for adults with attention-deficit/hyperactivity disorder ( ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01939353

Study of Flexible Doses of the Triple Reuptake Inhibitor EB ... This was a Phase 2 exploratory study to evaluate the efficacy and safety of EB-1020 SR (centanafadine sustained release [CTN SR]) in treating participants ...