ALTO-100 in Bipolar Disorder With Depression (BD-D)

A Randomized, Double-Blind, Placebo-Controlled Study Followed by Open-Label Treatment of ALTO-100 in Adults With Bipolar Disorder Currently Experiencing a Major Depressive Episode

The purpose of this study is to assess antidepressant efficacy differences between ALTO-100 and placebo during the Double-Blind period in patients with bipolar disorder I or II with current major depressive episode, when used adjunctively to a mood stabilizer and/or atypical antipsychotic, related to patient characteristics. Additionally, safety, tolerability, and efficacy will be assessed in a subsequent open label treatment period.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder I or II With a Major Depressive Episode
• Intervention / Treatment: Drug: Placebo; Drug: ALTO-100

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alto Neuroscience; Phone Number: 650-200-0412; Email: clinical@altoneuroscience.com

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Withdrawn
      • Site 6036
    • Phoenix, Arizona, United States, 85012
      • Recruiting
      • Site 6000
    • Yuma, Arizona, United States, 85364
      • Recruiting
      • Site 6087
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Recruiting
      • 6039
    • Little Rock, Arkansas, United States, 72204
      • Recruiting
      • 6070
  • California
    • Imperial, California, United States, 92251
      • Recruiting
      • Site 6081
    • Los Angeles, California, United States, 90025
      • Recruiting
      • 6069
    • Mather, California, United States, 95655
      • Not yet recruiting
      • Site 6016
    • Oceanside, California, United States, 92056
      • Recruiting
      • Site 6082
    • Riverside, California, United States, 92506
      • Recruiting
      • Site 6102
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Not yet recruiting
      • Site 6112
  • Florida
    • Lauderhill, Florida, United States, 33319
      • Withdrawn
      • Site 6067
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • Site 6068
    • Peachtree Corners, Georgia, United States, 30071
      • Recruiting
      • Site 6064
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Withdrawn
      • Site 6151
    • Bel Air, Maryland, United States, 21015
      • Recruiting
      • Site 6076
    • Gaithersburg, Maryland, United States, 20877
      • Recruiting
      • Site 6062
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Recruiting
      • Site 6142
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Recruiting
      • Site 6144
    • Las Vegas, Nevada, United States, 89119
      • Recruiting
      • Site 6104
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Recruiting
      • Site 6066
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Not yet recruiting
      • Site 6014
    • Albuquerque, New Mexico, United States, 87110
      • Recruiting
      • Site 6078
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Recruiting
      • 6065
    • Westlake, Ohio, United States, 44145
      • Recruiting
      • Site 6075
  • Texas
    • Houston, Texas, United States, 77081
      • Recruiting
      • Site 6072
  • Utah
    • Draper, Utah, United States, 84020
      • Not yet recruiting
      • Site 6121

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have a diagnosis of BD-I or BD-II as well as BD-D
• At baseline, taking a mood stabilizer, lithium (LI) or lamotrigine (LMG) or valproic acid (VPA, any form) or combination of Li + LMG or Li + VPA and/or taking an approved atypical antipsychotic medication (olanzapine, quetiapine, lurasidone, risperidone, ziprasidone, cariprazine, aripiprazole, lumateperone, and asenapine) 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
• Concurrent use of any prohibited medications or substance use disorder
• Diagnosed psychotic disorder (other than mania or depression)
• Current moderate or severe substance use disorder
• Has a history of hypersensitivity or allergic reaction to ALTO-100 or any of its components/excipients
• 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: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALTO-100; Participants will receive ALTO-100 40 mg tablet twice daily, from Day 1 to Week 6 in the double blind (DB) treatment period. Eligible participants who enter the open label (OL) treatment period will receive ALTO-100 40 mg tablet twice daily from OL baseline until the end of OL period/early termination visit (Up to 7 weeks).	Drug: ALTO-100; ALTO-100 40 mg tablet BID
Placebo Comparator: Placebo DB; Participants will receive matching placebo tablet twice daily, from Day 1 to Week 6 in the double blind (DB) treatment period.	Drug: Placebo; Placebo tablet BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess efficacy of ALTO-100 versus placebo on depression symptoms in bipolar disorder in a pre-defined subgroup of participants as measured by the mean change from Day 1 to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) total score	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 assessed from Day 1 to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess efficacy of ALTO-100 vs placebo for self-reported depressive symptoms in bipolar disorder patients in a pre- defined subgroup of participants as measured by the change from Day 1 to Week 6 in Patient Health Questionnaire, 9 item (PHQ-9)	The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the diagnostic and statistical manual of mental disorders-5th edition (DSM-5) major depressive disorder (MDD) criteria. Each item is rated on a 4- point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms.	Assessed 4 times over a 6-week interval, from Day 1 to Week 6
To assess efficacy of ALTO-100 vs placebo in severity of bipolar disorder symptoms in a pre-defined subgroup of participants as measured by the change from Day 1 to Week 6 in Clinician Global Impression Scale-severity (CGI-S)	The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of illness exhibited by a participant, rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill;5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores represent a more severe condition.	Assessed 4 times over a 6-week interval, from Day 1 to Week 6
To assess efficacy of ALTO-100 vs placebo for depressive symptoms in MDD in a pre-defined subgroup as measured by the change from Day 1 to Week 6 in response (>50% improvement from baseline) and remission (total score of <10) rates based on 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.	Assessed 4 times over a 6-week interval, from Day 1 to Week 6
To assess efficacy of ALTO-100 vs placebo on depressive symptoms in bipolar disorder in all randomized participants as measured by the change from Day 1 to Week 6 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.	Assessed 4 times over a 6-week interval, from Day 1 to Week 6
To evaluate the safety of ALTO-100 during both the DB and OL periods of the study as measured by the assessment of the incidence, severity, and relatedness of Treatment Emergent Adverse Events (TEAEs), SAEs, discontinuation due to TEAEs and deaths		Assessed from Day 1 to Week 13
To evaluate the safety of ALTO-100 during both the DB and OL periods of the study as measured by the assessment of Heart Rate in bpm	Assessment of Heart Rate in bpm	Assessed from Day 1 to Week 13
To evaluate the safety of ALTO-100 during both the DB and OL periods of the study as measured by the assessment of Blood Pressure in mmHg	Assessment of Blood Pressure in mmHg	Assessed from Day 1 to Week 13
To evaluate the safety of ALTO-100 during both the DB and OL periods of the study as measured by the assessment of Weight in pounds	Assessment of Weight in pounds	Assessed from Day 1 to Week 13
To evaluate the safety of ALTO-100 during both the DB and OL 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 0-4for 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 13

Collaborators and Investigators

• Sponsor: Alto Neuroscience
• Investigators: Study Director: Adam Savitz, MD, PhD, Alto Neuroscience

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 22, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Bipolar I; Bipolar II; Major Depressive Episode
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Bipolar Disorder; Depressive Disorder, Major
• Other Study ID Numbers: ALTO-100-211

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