Treatment Resistant Depression (TRD)Phase 3IRL Grey-CNCT07623135
Lumateperone for Late-Life Depression
A Phase 3 study testing Lumateperone in people with Treatment Resistant Depression (TRD) and Late Life Depression (LLD), run by Eric Lenze at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Treatment Resistant Depression (TRD), Late Life Depression (LLD), Depression / Major Depressive Disorder
- What is being tested?
- Lumateperone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Sep 2026to Jun 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Eric J Lenze, MD
- Recruiting
University of Arizona
Tucson, Arizona, 85713
Michael Miller, 520-626-7117, mmiller1@arizona.edu
Kai Glahn, 520-621-6731, xkg@arizona.edu
About this study
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).
Read the 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, the participant 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: The study team 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. The study team 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 the study team 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 their 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): The study team may ask participants to complete one additional endpoint visit for a final assessment of symptoms.
- Conditions
- Treatment Resistant Depression (TRD), Late Life Depression (LLD), Depression / Major Depressive Disorder
- Being tested
- Lumateperone, Placebo
- Keywords
- Late life depression treatment, Treatment resistant depression in older adults, major depression, lumateperone
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LumateperoneDrug
Also called Caplyta
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Montgomery-Asberg Depression Rating Scale (MADRS) total score
To evaluate whether adjunctive lumateperone reduces depressive symptoms compared with placebo.
Measured: From baseline to the end of treatment at week 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2026
- Study start1 Sep 2026
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant Depression (TRD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eric Lenze
- Sponsor type
- University, hospital or other
- Collaborators
- Intra-Cellular Therapies, Inc., Washington University School of Medicine
- Responsible party
- Sponsor-investigator, Eric Lenze, Washington University School of Medicine
- Investigators
- Eric J Lenze, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07623135
- Sponsor's protocol ID
- 202604086
- Acronym
- IRL Grey-C
- Status last verified
- Aug 2026
- First submitted
- 28 May 2026
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Contact PI
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lumateperone for Late-Life Depression
- ClinicalTrials.gov ID
- NCT07623135
- Acronym / sponsor ID
- IRL Grey-C / 202604086
- Conditions
- Treatment Resistant Depression (TRD), Late Life Depression (LLD), Depression / Major Depressive Disorder
- Keywords
- Late life depression treatment, Treatment resistant depression in older adults, major depression, lumateperone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Eric LenzeUniversity, hospital or other
- Collaborators
- Intra-Cellular Therapies, Inc., Washington University School of Medicine
- Study start
- 1 Sep 2026 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 3 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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, the participant 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: The study team 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. The study team 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 the study team 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 their 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): The study team may ask participants to complete one additional endpoint visit for a final assessment of symptoms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lumateperone | Experimental | Drug: LumateperoneThe 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 | Placebo comparator | Drug: PlaceboThe 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. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LumateperoneAlso: CaplytaParticipants 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. | Drug | Lumateperone |
| PlaceboParticipants 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. | Drug | Placebo |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Individual participant dataSharing planned: Yes. Contact PI
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eric J Lenze, MD principal investigator
Washington University School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lumateperone in people with Treatment Resistant Depression (TRD) and Late Life Depression (LLD), run by Eric Lenze at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Angela Stevens (314-362-6291, stevens.a@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.