Recruiting

NCT Number: NCT06656416

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

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.

Recruiting

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Key information

Conditions

Bipolar Disorder I or II With a Major Depressive Episode

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Site 6036, Chandler, Arizona, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ALTO-100

Drug

ALTO-100 40 mg tablet BID

Placebo

Drug

Placebo tablet BID

Primary outcomes

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

Time frame: Change assessed from Day 1 to Week 6

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.

Secondary outcomes

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)

Time frame: Assessed 4 times over a 6-week interval, from Day 1 to Week 6

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.
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)

Time frame: Assessed 4 times over a 6-week interval, from Day 1 to Week 6

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.
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

Time frame: Assessed 4 times over a 6-week interval, from Day 1 to Week 6

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.
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

Time frame: Assessed 4 times over a 6-week interval, from Day 1 to Week 6

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.
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

Time frame: 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

Time frame: Assessed from Day 1 to Week 13

Assessment of Heart Rate in bpm
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

Time frame: Assessed from Day 1 to Week 13

Assessment of Blood Pressure in mmHg
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

Time frame: Assessed from Day 1 to Week 13

Assessment of Weight in pounds
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)

Time frame: Assessed from Day 1 to Week 13

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.

Study contacts

Contact information is provided by the study sponsor or research team.

Alto Neuroscience

CONTACT

[email protected]

650-200-0412

Sponsors and collaborators

Lead sponsor

Alto Neuroscience

Industry

Registry information

Official study title

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

Important dates

Study start: 2024
Primary completion: 2026
Study completion: 2026
First posted: Oct 24, 2024
Registry last updated: Jul 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Key information

Conditions

Age range

Sex eligibility

Study type

Phase

Primary location

Who can participate

Treatment and study plan

ALTO-100

Placebo

Primary outcomes

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

Secondary outcomes

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)

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)

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

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

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

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

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

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

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)