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Assessing a new buccal film treatment for treatment resistant depression

A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Trial to Assess the Efficacy, Safety, and Tolerability of Repeated Doses of VLS-01 Buccal Film in Participants With Treatment Resistant Depression

Phase 2 Interventional atai Therapeutics, Inc. · NCT06524830

This study is testing a new buccal film treatment for people with treatment-resistant depression to see if it can help improve their symptoms better than a placebo.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment142 (estimated)
Ages18 Years to 65 Years
SexAll
Sponsoratai Therapeutics, Inc. Industry-sponsored
Locations48 sites (Tucson, Arizona and 47 other locations)
Trial IDNCT06524830 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial evaluates the efficacy, safety, and tolerability of VLS-01, a transmucosal buccal film, in patients suffering from treatment resistant major depressive disorder (TRD). Approximately 142 participants will be randomly assigned to receive either the VLS-01 buccal film or a placebo in a double-blind manner, with two administrations spaced two weeks apart. Following the initial treatment phase, participants will be monitored for 12 weeks to assess symptom changes, after which they will receive a third dose of VLS-01-BU. The study aims to characterize the onset and durability of the antidepressant effects compared to placebo.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with a diagnosis of recurrent moderate or severe major depressive disorder who have not responded to multiple antidepressant treatments.

Not a fit: Patients with psychotic disorders or those who have not experienced a major depressive episode for at least three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with treatment resistant depression who have not responded to traditional antidepressants.

How similar studies have performed: While there have been studies on various treatments for depression, the specific approach of using a buccal film for treatment resistant depression is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Participant must be 18 to 65 years of age inclusive at the time of signing the Informed Consent.
* Has a diagnosis of recurrent moderate or severe MDD without psychotic features or single- episode MDD with duration greater than or equal to 3 months without psychotic features and is currently experiencing a major depressive episode.
* Onset of first episode of MDD occurred before age 55.
* Has not responded to an adequate dose and duration of at least two and no more than five antidepressant medications for the current depressive episode, as determined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH- ATRQ).
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

Exclusion Criteria:

* Has a current or prior DSM-5-TR diagnosis of a schizophrenia spectrum and other psychotic disorder, substance/medication-induced psychotic disorder, bipolar and related disorder, or any disorder with psychotic features.
* Has a moderate or severe substance use disorder (drug, alcohol, or tobacco) within the 6 months before Screening and/or history of moderate or severe substance use disorder (drug alcohol) within the previous 1 year before Screening
* Has a history of, or current signs and symptoms of, diseases or conditions that would make participation not be in the best interest (e.g., compromise the wellbeing) of the participant or that could prevent, limit, or confound the protocol-specified assessments.
* Has suicidal ideation with some intent to act within 6 months before Screening or a history of suicidal behavior within the past 1 year before Screening.
* Has a history of clinically significant cardiovascular, cerebrovascular, or peripheral vascular disease or condition, including but not limited to unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, valvular heart disease, obstructive coronary artery disease, hypertension, hypotension, bradycardia, tachycardia, or risk factors for long QT Syndrome.
* Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years before Screening.
* Has any known allergy or hypersensitivity to VLS-01 or to any of the excipients in the formulation.
* Has recently initiated and is currently undergoing directive psychotherapy (e.g., cognitive behavioral therapy, interpersonal psychotherapy, psychodynamic psychotherapy) within the past 30 days before Screening. Participants planning to initiate individual or group therapy during the study are also not eligible.
* Has received any prohibited therapies.
* Has clinically significant laboratory abnormalities at Screening.

Where this trial is running

Tucson, Arizona and 47 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Treatment Resistant DepressionMajor DepressionMood DisordersMental DisordersDepressive DisorderDepressionDepressive Disorder, MajorAntidepressive Agents
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.