Lumateperone for Late-Life Depression (IRL Grey-C)

May 28, 2026 updated by: Eric Lenze
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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study is a 10-week, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of adjunctive lumateperone in older adults with treatment-resistant depression (TRD). Approximately 100 participants aged ≥60 years with unipolar, non-psychotic major depressive disorder will be enrolled across two study sites. Participants will continue their existing antidepressant medication at a stable dose throughout the study and will be randomized to receive either lumateperone or matching placebo administered adjunctively during the treatment phase.

  • Screening: Participants who sign consent will go through a screening process. This will involve answering questions about medical history, medications, demographics, mood and emotions as well as completing a brief cognitive test.
  • Baseline: If the participant is eligible from the screening visit, they will complete a baseline visit in our research clinic. This will involve answering questions and completing questionnaires about mood and emotions, completing tasks on an iPad to assess thinking, attention, and memory as well as a physical exam. The physical exam will include gathering height and weight, an evaluation for potential medication side effects, a fasting blood draw to measure blood lipids and glucose, and an electrocardiogram (ECG).
  • Study Medication: Participants will be randomized (like flipping a coin) to take either lumateperone or placebo (sugar pill). The research team and participant will be blinded to each participant's study medication. Participants will not get to choose whether they take lumateperone or placebo.
  • Monitoring visits: We will ask participants to complete visits in the research clinic after one week, two weeks, four weeks, six weeks, and eight weeks following the baseline visit. These visits will be to assess depression symptoms, medication changes, and side effects. We may ask participants to complete additional visits in person or over the phone if they are needed to manage side effects or worsening in depressive symptoms.
  • Endpoint visit: After 10-weeks we will ask participants to complete an endpoint visit in the research clinic to measure the effects of lumateperone or placebo. This visit includes answering questions and completing questionnaires about mood and emotions, medication changes, and side effects. Participants will complete tasks on an iPad to assess your thinking, attention, and memory. There will also be a fasting blood draw to measure blood lipids and glucose as well as another ECG.
  • Extra visit (if needed): We may ask participants to complete one additional endpoint visit for a final assessment of symptoms.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85713
        • University of Arizona
        • Principal Investigator:
          • Jordan Karp, MD
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
        • Principal Investigator:
          • Eric J Lenze, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lumateperone
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
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.
Other Names:
  • Caplyta
Placebo Comparator: Placebo
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
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) total score
Time Frame: From baseline to the end of treatment at week 10.
To evaluate whether adjunctive lumateperone reduces depressive symptoms compared with placebo.
From baseline to the end of treatment at week 10.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eric Lenze

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Intra-Cellular Therapies, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Eric J Lenze, MD, Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 28, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 3, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202604086

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Contact PI

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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