ALTO-300 for Depression

No longer recruiting at 10 trial locations

Overseen By Lesley Parker

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alto Neuroscience

Must be taking: SSRI, SNRI, Bupropion

Must not be taking: TCAs, MAOIs, Antipsychotics, others

Disqualifiers: Liver disease, Bipolar, Psychotic disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication called ALTO-300 (also known as Agomelatine) to evaluate its effects on people with depression. Researchers aim to understand how this treatment works and identify who might benefit most by analyzing biological data. It suits individuals diagnosed with moderate to severe depression who are on a stable dose of specific antidepressants, such as SSRIs or SNRIs, but still experience significant symptoms. Participants should be willing to use a smartphone for activity and sleep monitoring during the study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You can continue taking your current SSRI, SNRI, or bupropion if you've been on a stable dose for at least 6 weeks. However, you cannot use certain other medications like tricyclic antidepressants, melatonin, or antipsychotics during the trial.

Is there any evidence suggesting that ALTO-300 is likely to be safe for humans?

Research has shown that ALTO-300 is generally safe for people. In a previous study, the most common side effect was a headache. This indicates that while some might experience mild discomfort, no serious safety issues were reported. Additionally, long-term checks have shown that ALTO-300 rarely affects the liver, supporting its strong safety profile. This makes ALTO-300 a promising option for treating depression. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ALTO-300 for depression because it offers a new approach compared to standard treatments like SSRIs and SNRIs. Unlike these medications, which primarily target neurotransmitters like serotonin and norepinephrine, ALTO-300 employs a novel mechanism of action that could potentially address depression symptoms more effectively. Additionally, ALTO-300 is an oral tablet taken daily, which could improve patient adherence and convenience. This innovative treatment holds promise for those who haven't found relief with existing options.

What evidence suggests that ALTO-300 might be an effective treatment?

Research suggests that ALTO-300 could help treat depression. In earlier studies, participants taking a 25mg dose of ALTO-300 generally tolerated it well, experiencing no major side effects. Although detailed information on its effectiveness for depression is not yet available, the current trial compares ALTO-300 to a placebo to assess its efficacy. The trial aims to determine if ALTO-300 can improve symptoms of depression when used alongside regular antidepressants. This trial explores how ALTO-300 might enhance well-being for those dealing with depression. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

Inclusion Criteria

Have a diagnosis of moderate to severe major depressive disorder

I am willing to comply with all study assessments and procedures.

A woman is not allowed to be pregnant or breastfeeding at the time of enrollment or throughout the study.

Exclusion Criteria

You have a serious problem with alcohol.

You are currently having thoughts of wanting to harm yourself.

Evidence of liver impairment or disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Treatment

Participants receive ALTO-300 oral tablet daily for 8 weeks

8 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALTO-300

How Is the Trial Designed?

Group I: ALTO-300 Experimental Treatment 1 Intervention

ALTO-300 oral (PO) tablet; daily dosing 8 weeks

ALTO-300 is already approved in European Union for the following indications:

Approved in European Union as Valdoxan for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Alto Neuroscience

Lead Sponsor

Trials

11

Recruited

1,300+

Citations

1. investors.altoneuroscience.com investors.altoneuroscience.com/news/news-details/2025/Alto-Neuroscience-Presents-Data-at-the-2025-American-Society-of-Clinical-Psychopharmacology-Annual-Meeting-Reinforcing-Safety-and-Tolerability-Profile-for-ALTO-300-in-Major-Depressive-Disorder/default.aspx

News Details Completed Phase 2a and ongoing Phase 2b trial of ALTO-300 in MDD underscore favorable tolerability profile for 25mg dose.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05922878

NCT05922878 | Study of ALTO-300 in MDD The purpose of this study is to determine efficacy differences between ALTO-300 and placebo, used adjunctively to an antidepressant, related to patient ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4014359/

Efficacy and tolerability of agomelatine in the treatment of ... From among eight completed trials involving major depressive disorder, four produced positive results for agomelatine while three of the original placebo- ...

4. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-03951-0

Agomelatine as adjunctive therapy with SSRIs or SNRIs for ... Additionally, agomelatine did not show a statistically significant effect on secondary outcomes, including the remission and response rates ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1134593425000442

Comparing the effectiveness of agomelatine, bupropion ... The results showed that agomelatine was significantly more effective than placebo and contributed to the improvement of depressive symptoms. Additionally, the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7816263/

The safety of agomelatine in standard medical practice in ... Adverse events reported were in accordance with the known safety profile of agomelatine. Cutaneous events were reported in 1.7% of the patients ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05118750

Study Details | NCT05118750 | ALTO-300 in Depression The purpose of this study is to collect biologically-based data for defining predictors and correlates of the effects of ALTO-300.

8. altoneuroscience.com altoneuroscience.com/wp-content/uploads/2025/05/2025_ASCP_ALTO-300-Safety-and-Biomarker-Evidence_FINAL.pdf

ALTO-300 as Adjunctive Treatment for Major Depressive ... • Low rates of LFT elevation and no safety issues in data from tens of thousands of patients in long-term monitoring trials and real-world data demonstrate:.

9. mdpi.com mdpi.com/1422-0067/25/23/12631

Efficacy and Safety of Agomelatine in Depressed Patients ... The purpose of this study was to systematically review and meta-analyze data on the efficacy and safety of agomelatine (AGO) in the treatment of patients with ...