Lumateperone for Late-Life Depression

NCT07623135 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: 202604086
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to examine how well a medication called lumateperone (Caplyta) works to relieve depression in older adults with treatment-resistant depression. Lumateperone (Caplyta) is approved by the U.S. Food and Drug Administration to treat Major Depressive Disorder in adults who are also taking another antidepressant medication. This study will compare lumateperone (Caplyta) to placebo (a sugar pill without medication).

Conditions

Late Life Depression (LLD); Treatment Resistant Depression (TRD); Depression / Major Depressive Disorder

Keywords

Late life depression treatment; Treatment resistant depression in older adults; major depression; lumateperone

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) total score

  To evaluate whether adjunctive lumateperone reduces depressive symptoms compared with placebo.

  From baseline to the end of treatment at week 10.

Study Arms (2)

Lumateperone

EXPERIMENTAL

The starting dose of lumateperone or placebo will typically be 21 mg/day for the first week. Those participants who are taking moderate or strong CYP3A4 inhibitors will start at 10.5 mg/ day. The dose will be increased for most participants to 42 mg/ day at Week 2 and maintained until Week 10. Participants with moderate or severe hepatic impairment (Child-Pugh class B or C) will be maintained at 21 mg/day. Participants who are taking strong CYP3A4 inhibitors will be maintained at 10.5 mg/ day. Participants who are taking moderate CYP3A4 inhibitors will increase as tolerated to 21 mg/ day.

Drug: Lumateperone

Placebo

PLACEBO COMPARATOR

The starting dose of lumateperone or placebo will typically be 21 mg/day for the first week. Those participants who are taking moderate or strong CYP3A4 inhibitors will start at 10.5 mg/ day. The dose will be increased for most participants to 42 mg/ day at Week 2 and maintained until Week 10. Participants with moderate or severe hepatic impairment (Child-Pugh class B or C) will be maintained at 21 mg/day. Participants who are taking strong CYP3A4 inhibitors will be maintained at 10.5 mg/ day. Participants who are taking moderate CYP3A4 inhibitors will increase as tolerated to 21 mg/ day.

Drug: Placebo

Interventions

Lumateperone DRUG

Participants will be randomized to take either lumateperone or placebo along with their existing antidepressant for 10 weeks. Dose will range from 10.5mg-42mg over the course of the study.

Also known as: Caplyta

Lumateperone

Placebo DRUG

Participants will be randomized to take either lumateperone or placebo along with their existing antidepressant for 10 weeks. Dose will range from 10.5mg-42mg over the course of the study.

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>=60
• Current unipolar non-psychotic major depression determined by SCID-5
• MADRS score \>=20 at screening and \>=18 at baseline
• Treatment-resistance defined as documented history of non-response to at least two oral medications of adequate dose and duration in this episode or previous episode, OR clinician determination that treatment augmentation is appropriate
• Currently taking oral antidepressant prescribed at least minimum therapeutic dose and for at least six weeks duration
• MMSE score of \>/=24

You may not qualify if:

• Dementia
• High risk for suicide, defined as a 4 or 5 on C-SSRS (indicating active suicidal ideation with current or recent intent or plan), and unable to be managed safely in the clinical trial. Urgent psychiatric referral will be made in these cases.
• High risk alcohol use: defined as a score of 6 or more on the AUDIT-C
• Medically inappropriate for participation as determined by PIs.

Sponsors & Collaborators

• Eric Lenze: lead
• Intra-Cellular Therapies, Inc.: collaborator

Study Sites (2)

University of Arizona

Tucson, Arizona, 85713, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression; Depressive Disorder, Major

Interventions

lumateperone

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Eric J Lenze, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Kinghorn, MS

CONTACT

314-362-8761; akinghorn@wustl.edu

Julie Schweiger

CONTACT

314-362-3153; schweigj@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Wallace and Lucille K Renard Prof of Psychiatry

Study Record Dates

• First Submitted: May 28, 2026
• First Posted: June 3, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (2)