PD, PK, and Safety of ALTO-203 in Patients With MDD

Double-Blind, Single and Multiple Dose Study to Determine Pharmacodynamic Markers, Pharmacokinetic Parameters, and Safety of ALTO-203 in Patients With Major Depressive Disorder

The goal of this clinical trial is to determine the pharmacodynamic effects of ALTO-203 in patients with MDD in a randomized, placebo-controlled, single-dose crossover treatment period. Additionally, safety, tolerability, and PK will be assessed in a subsequent randomized placebo-controlled multi-dose parallel-group treatment period of 28 days.

Participants will complete subjective response questionnaires and perform cognitive tasks during the single-dose period, in which participants will receive ALTO-203 25 μg and 75 μg, as well as placebo. During the multiple-dose period, participants will receive either ALTO-203 25 μg, 75 μg , or placebo. Safety will be assessed over the single dose and 28-day multiple dose periods.

Study Overview

• Status: Completed
• Conditions: Anhedonia; Major Depressive Disorder
• Intervention / Treatment: Drug: ALTO-203 25 μg; Drug: ALTO-203 75 μg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Site 4058
  • California
    • Oceanside, California, United States, 92056
      • Site 4082
    • Torrance, California, United States, 90504
      • Site 4023
  • Florida
    • Clermont, Florida, United States, 34711
      • Site 4059
    • Orlando, Florida, United States, 32801
      • Site 4005
  • Georgia
    • Atlanta, Georgia, United States, 30030
      • Site 4031
  • Maryland
    • Pikesville, Maryland, United States, 21208
      • Site 4054
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Site 4036
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Site 4022
    • Princeton, New Jersey, United States, 08540
      • Site 4134
  • Ohio
    • Westlake, Ohio, United States, 44145
      • Site 4075
  • Texas
    • Austin, Texas, United States, 78737
      • Site 4040
    • Houston, Texas, United States, 77081
      • Site 4072
  • Utah
    • Clinton, Utah, United States, 84015
      • Site 4007
  • Washington
    • Bellevue, Washington, United States, 98007
      • Site 4033

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a diagnosis of moderate major depressive disorder (MDD)
• Presence of anhedonia symptoms
• Not taking antidepressant at Screening Visit 2
• Willing to comply with all study assessments and procedures

Exclusion Criteria:

• Evidence of unstable medical condition
• Diagnosed bipolar disorder, psychotic disorder, or dementia
• Concurrent use of prohibited medications
• Current moderate or severe substance use disorder
• Concurrent or recent participation in another clinical trial for mental illness involving an investigational product or device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALTO-203 25 μg; Drug: ALTO-203 25 μg Single-Dose Treatment Period: Single Dose, ALTO-203 25 μg Multi-Dose Treatment Period: ALTO-203 25 μg, administered orally, once daily for 28 days	Drug: ALTO-203 25 μg; Active, ALTO-203 25 μg
Experimental: ALTO-203 75 μg; Drug: ALTO-203 75 μg Single-Dose Treatment Period: Single Dose, ALTO-203 75 μg Multi-Dose Treatment Period: ALTO-203 75 μg, administered orally, once daily for 28 days	Drug: ALTO-203 75 μg; Active, ALTO-203 75 μg
Placebo Comparator: Placebo; Drug: Placebo Single-Dose Treatment Period: Single Dose, Placebo Multi-Dose Treatment Period: Placebo, administered orally, once daily for 28 days	Drug: Placebo; Comparator, Placebo-to-match

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single Dose Period: To evaluate pharmacodynamic measures in patients with MDD after single doses of 25 μg ALTO-203, 75 μg ALTO-203, and placebo as measured by the alertness and mood components of the Bond-Lader Visual Analog Scale (BL-VAS).	The Bond-Lader Visual Analogue Scale (BL-VAS) is used to measure the effects of drugs on the participants' mood. It consists of 16 VAS measurements of different mood state. For each question, the participants will rate their feelings at the time of assessment by indicating the point on the 10 cm line which best represents their mood. Each item is scored by measuring the position relative to the left-hand end of the line. The combined domains of alertness and mood will be assessed for the primary endpoint.	Single-Dose Treatment Period - Pre-Dose, 1.5 hours, 3 hours, and 5 hours on Day 1 at Treatments 1, 2, and 3
Multi-Dose Period: To assess the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] during the multi-dose treatment period for ALTO-203 25 μg and ALTO-203 75 μg as compared to placebo.	Incidence, severity, and relatedness of TEAEs, SAEs, discontinuation due to TEAEs.	Multi-Dose Treatment Period Day 1 to Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single Dose Period: To assess the incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] during the single-dose treatment period for ALTO-203 25 μg and ALTO-203 75 μg as compared to placebo.	Incidence, severity, and relatedness of TEAEs, SAEs, discontinuation due to TEAEs.	Single-Dose Treatment Period Day 1 to Day 21
Multi-Dose Period: To understand the pharmacokinetics (PK) of multi-doses of ALTO-203 in capsule formulation	Bioanalysis of plasma samples and observed plasma concentrations of ALTO-203 after multiple days of dosing.	Multi-Dose Treatment Period Day 1 to Day 35

Collaborators and Investigators

• Sponsor: Alto Neuroscience

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2024
• Primary Completion (Actual): April 14, 2025
• Study Completion (Actual): April 21, 2025

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Neurobehavioral Manifestations; Mood Disorders; Depressive Disorder; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Depressive Disorder, Major; Anhedonia
• Other Study ID Numbers: ALTO-203-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No