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

NCT06391593 | Completed Phase 2 FDA Drug

• 1 other identifier: ALTO-203-201
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Major Depressive Disorder; Anhedonia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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.

  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

  Multi-Dose Treatment Period Day 1 to Day 35

Study Arms (3)

ALTO-203 25 μg

EXPERIMENTAL

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

ALTO-203 75 μg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Drug: Placebo Single-Dose Treatment Period: Single Dose, Placebo Multi-Dose Treatment Period: Placebo, administered orally, once daily for 28 days

Drug: Placebo

Interventions

ALTO-203 25 μg DRUG

Active, ALTO-203 25 μg

ALTO-203 25 μg

ALTO-203 75 μg DRUG

Active, ALTO-203 75 μg

ALTO-203 75 μg

Placebo DRUG

Comparator, Placebo-to-match

Placebo

Eligibility Criteria

• Age: 25 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alto Neuroscience: lead

Study Sites (15)

Site 4058

Tucson, Arizona, 85704, United States

Location

Site 4082

Oceanside, California, 92056, United States

Location

Site 4023

Torrance, California, 90504, United States

Location

Site 4059

Clermont, Florida, 34711, United States

Location

Site 4005

Orlando, Florida, 32801, United States

Location

Site 4031

Atlanta, Georgia, 30030, United States

Location

Site 4054

Pikesville, Maryland, 21208, United States

Location

Site 4036

Las Vegas, Nevada, 89121, United States

Location

Site 4022

Marlton, New Jersey, 08053, United States

Location

Site 4134

Princeton, New Jersey, 08540, United States

Location

Site 4075

Westlake, Ohio, 44145, United States

Location

Site 4040

Austin, Texas, 78737, United States

Location

Site 4072

Houston, Texas, 77081, United States

Location

Site 4007

Clinton, Utah, 84015, United States

Location

Site 4033

Bellevue, Washington, 98007, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will consist of two treatment periods. The initial Single-Dose Treatment Period is a randomized, double-blind, placebo-controlled 3-way crossover design with oral administration of a single dose of ALTO-203 25 μg, ALTO-203 75 μg, and matching placebo. In the subsequent Multi-Dose Parallel-Group Treatment Period, participants will receive ALTO-203 25 μg, ALTO-203 75 μg, or matching placebo randomized 1:1:1 for a total of 28 days.

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 30, 2024
• Study Start: March 25, 2024
• Primary Completion: April 14, 2025
• Study Completion: April 21, 2025
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)