Recruiting
Phase 3

Lumateperone

Sponsor:

Eric Lenze

Code:

NCT07623135

Conditions

Treatment Resistant Depression (TRD)

Late Life Depression (LLD)

Depression / Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Not accepted

Interventions

Lumateperone

Placebo

Study Details

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

Treatment Resistant Depression (TRD)

Late Life Depression (LLD)

Depression / Major Depressive Disorder

Study ID

NCT07623135

Start date

Aug, 2026

Status verified date

Aug, 2026

Completion date

Jun, 2028

Anticipated

Primary completion date

Jun, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Not accepted

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 Design

Enrollment

100 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

Interventions

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.

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.

Primary outcome measure

  • Change in Montgomery-Asberg Depression Rating Scale (MADRS) total score [ Time Frame: From baseline to the end of treatment at week 10. ]

Central Contacts and Locations

Central contacts

Angela Stevens

314-362-6291stevens.a@wustl.edu

Julie Schweiger

314-362-3153schweigj@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Principal Investigator:

Eric J Lenze, MD

More Information

Sponsor

Eric Lenze

Last update posted

Aug 6, 2026

Last verified

Aug, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Eric Lenze on 2026-08-06.