Study of ALTO-300 in MDD

Study Overview
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Brief Summary
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The purpose of this study is to determine efficacy differences between ALTO-300 and placebo, used adjunctively to an antidepressant, related to patient characteristics.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of ALTO-300 With an Open-Label Extension in Adults With Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: ALTO-300
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of moderate to severe major depressive disorder (MDD) At Visit 2, currently taking a single SSRI, SNRI, or bupropion for at least 6 weeks with no dose modifications in the past 2 weeks Willing to comply with all study assessments and procedures Must not be pregnant or breastfeeding at time of enrollment or throughout study Exclusion Criteria: Evidence of unstable medical condition Nightly use of sleep medication Diagnosed bipolar disorder, psychotic disorder, or dementia Current moderate or severe substance use disorder Has a history of hypersensitivity or allergic reaction to ALTO-300 or any of its components/excipients Concurrent or recent participation in another clinical trial for mental illness involving an investigational product or device

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALTO-300<br>Participants will receive ALTO-300 capsule once daily in the evening, from Day 1 to Day 42 in double blind (DB) treatment period. Eligible participants who will enter the open-label (OL) treatment period will receive ALTO-300 capsule once daily in the evening from OL baseline until the end of OL period/early termination visit (Up to 8 weeks). | Drug: ALTO-300<br>* ALTO-300 capsule QD<br>|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo capsule once daily in the evening, from Day 1 to Day 42 in double blind (DB) treatment period. | Drug: Placebo<br>* Placebo capsule QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess efficacy of adjunctive ALTO-300 versus placebo on symptoms of MDD in a pre-defined subgroup of participants as measured by the change over time up to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS). | MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. | Change over time for up to week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess efficacy of adjunctive ALTO-300 versus placebo on symptoms of MDD in all randomized participants as measured by the change over time up to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) | MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. | Change over time for up to week 6 | 
| To assess efficacy of adjunctive ALTO-300 versus placebo for MDD as measured by the change over time up to week 6 in response (>50% improvement from baseline) rates based on the MADRS | MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. | Change over time for up to week 6 | 
| To evaluate the safety of ALTO-300 during both the OL and DB periods of the study as measured by the assessment of the incidence, severity, and relatedness of Adverse Events. | Incidence, severity, and relatedness of Adverse Events | Assessed from Day 1 to Week 14 | 
| To evaluate the safety of ALTO-300 during both the OL and DB periods of the study as measured by the assessment of Heart Rate. | Assessment of Heart Rate | Assessed from Day 1 to Week 14 | 
| To evaluate the safety of ALTO-300 during both the OL and DB periods of the study as measured by the assessment of Weight. | Assessment of Weight | Assessed from Day 1 to Week 14 | 
| To evaluate the safety of ALTO-300 during both the OL and DB periods of the study as measured by the assessment of Blood Pressure. | Assessment of Blood Pressure | Assessed from Day 1 to Week 14 | 
| To evaluate the safety of ALTO-300 during both the OL and DB periods of the study as measured by the assessment of suicidality with the Concise Health Risk Tracking Self-Report,12 item scale (CHRT-SR12). | The CHRT is a brief, self-report measure that systematically assesses both suicidal thinking and associated thoughts that may indicate the propensity for suicidal acts. The CHRT-SR12 is a 12 item scale. The patient assigns a score of 0-4 for each item of the scale, allowing for a total score of 0 to 48, with the higher score signifying more severe symptoms. | Assessed from Day 1 to Week 15 |