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

NCT06656416 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ALTO-100-211
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 27

Brief Summary

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.

Conditions

Bipolar Disorder I or II With a Major Depressive Episode

Keywords

Bipolar I; Bipolar II; Major Depressive Episode

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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)

  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)

  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

  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

  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

Study Arms (2)

ALTO-100

EXPERIMENTAL

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

Placebo DB

PLACEBO COMPARATOR

Participants will receive matching placebo tablet twice daily, from Day 1 to Week 6 in the double blind (DB) treatment period.

Drug: Placebo

Interventions

ALTO-100 DRUG

ALTO-100 40 mg tablet BID

ALTO-100

Placebo DRUG

Placebo tablet BID

Placebo DB

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alto Neuroscience: lead

Study Sites (27)

Site 6036

Chandler, Arizona, 85224, United States

WITHDRAWN

Site 6000

Phoenix, Arizona, 85012, United States

RECRUITING

Site 6087

Yuma, Arizona, 85364, United States

RECRUITING

6039

Fayetteville, Arkansas, 72703, United States

RECRUITING

6070

Little Rock, Arkansas, 72204, United States

RECRUITING

Site 6081

Imperial, California, 92251, United States

RECRUITING

6069

Los Angeles, California, 90025, United States

RECRUITING

Site 6016

Mather, California, 95655, United States

NOT YET RECRUITING

Site 6082

Oceanside, California, 92056, United States

RECRUITING

Site 6102

Riverside, California, 92506, United States

RECRUITING

Site 6112

Colorado Springs, Colorado, 80910, United States

NOT YET RECRUITING

Site 6067

Lauderhill, Florida, 33319, United States

WITHDRAWN

Site 6068

Atlanta, Georgia, 30328, United States

RECRUITING

Site 6064

Peachtree Corners, Georgia, 30071, United States

RECRUITING

Site 6151

Baltimore, Maryland, 21229, United States

WITHDRAWN

Site 6076

Bel Air, Maryland, 21015, United States

RECRUITING

Site 6062

Gaithersburg, Maryland, 20877, United States

RECRUITING

Site 6142

Lincoln, Nebraska, 68526, United States

RECRUITING

Site 6144

Las Vegas, Nevada, 89102, United States

RECRUITING

Site 6104

Las Vegas, Nevada, 89119, United States

RECRUITING

Site 6066

Toms River, New Jersey, 08755, United States

RECRUITING

Site 6014

Albuquerque, New Mexico, 87108, United States

NOT YET RECRUITING

Site 6078

Albuquerque, New Mexico, 87110, United States

RECRUITING

6065

North Canton, Ohio, 44720, United States

RECRUITING

Site 6075

Westlake, Ohio, 44145, United States

RECRUITING

Site 6072

Houston, Texas, 77081, United States

RECRUITING

Site 6121

Draper, Utah, 84020, United States

NOT YET RECRUITING

Study Officials

• Adam Savitz, MD, PhD

  Alto Neuroscience

  STUDY DIRECTOR

Central Study Contacts

Alto Neuroscience

CONTACT

650-200-0412; clinical@altoneuroscience.com

Study Design

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

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 24, 2024
• Study Start: October 2, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (27)