Dopamine Receptor Agonist for Schizophrenia

Recruiting at 3 trial locations

Overseen By John Krystal, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yale University

Must not be taking: Olanzapine, Clozapine, Ziprasidone, Asenapine

Disqualifiers: Unstable conditions, Neurological disease, Cardiac disease, Substance use, others

Compensation: Varies

Number of Visits: 5

Duration: 5 weeks

112 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests CVL-562, a new medicine that helps activate brain receptors related to dopamine, in patients with early episode schizophrenia who have memory problems. The goal is to see if it can improve their thinking and memory by enhancing brain activity.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable psychotropic medication regimen for at least 3 weeks before starting and during the study. However, you cannot be on certain medications like olanzapine, clozapine, ziprasidone, or asenapine, and must avoid certain other medications or substances 10 days before and during the study.

What data supports the effectiveness of the drug CVL-562 (PF-06412562) for treating schizophrenia?

The drug PF-06412562 is a selective dopamine D1/D5 receptor partial agonist, which means it can help improve cognitive function in schizophrenia by partially activating specific dopamine receptors in the brain. This approach is being evaluated for its potential to address cognitive impairments associated with schizophrenia. ^{1 2 3 4 5}

Is CVL-562 (PF-06412562) safe for humans?

CV 205-502, a similar dopamine agonist, has been studied in various conditions and generally found to be safe and well-tolerated in humans, with mild side effects like nausea and low blood pressure reported in some cases. ^{2 6 7 8 9}

What makes the drug CVL-562 (PF-06412562) unique for treating schizophrenia?

CVL-562 (PF-06412562) is unique because it acts as a dopamine receptor agonist, specifically targeting D2 receptors, which are often elevated in schizophrenia. This mechanism is different from many traditional antipsychotics that primarily block these receptors, potentially offering a novel approach to managing symptoms. ^{1 5 10 11 12}

Research Team

John Krystal, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for individuals aged 18-45 with early episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. They must be fluent in English, not pregnant or planning to become so during the study, and on stable psychiatric medication for at least two months. Participants should have no significant medical conditions that could interfere with the study.

Inclusion Criteria

Demonstrate a premorbid IQ of ≥80 based on the Penn Reading Assessment (PRA)

I am between 18 and 45 years old.

I can follow simple instructions and move as needed for a memory task.

Exclusion Criteria

I am allergic or react badly to certain medications.

I have a history of serious heart problems.

Any unstable medical, psychiatric, or neurological condition (including active or otherwise remarkable suicidal or homicidal ideation) that may necessitate urgent treatment. Active medical conditions that are minor or well controlled are not exclusionary if they do not affect risk to the patient, metabolism of study drug, or the study results (e.g. well-controlled type II diabetes or hypertension) as per the judgment of the investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CVL-562 (PF-06412562) at different doses or placebo over 5 test visits, with repeated fMRI and cognitive testing

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CVL-562 (PF-06412562) 15 mg
• CVL-562 (PF-06412562) 1 mg
• CVL-562 (PF-06412562) 25 mg
• CVL-562 (PF-06412562) 4 mg
• Placebo

Trial Overview The trial is testing CVL-562 (PF-06412562), a dopamine receptor partial agonist at different doses (1 mg, 4 mg, 15 mg, and 25 mg) against a placebo. It aims to see if this drug can improve working memory by engaging certain brain receptors using neuroimaging as a measure of effectiveness.

Participant Groups

Group I: CVL-562 (PF-06412562) 4 mg Experimental Treatment 1 Intervention

Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.

Group II: CVL-562 (PF-06412562) 25 mg Experimental Treatment 1 Intervention

Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.

Group III: CVL-562 (PF-06412562) 15 mg Experimental Treatment 1 Intervention

Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.

Group IV: CVL-562 (PF-06412562) 1 mg Experimental Treatment 1 Intervention

Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.

Group V: Placebo Placebo Group 1 Intervention

Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Subjects will be randomized to the order of doses of CVL-562 (PF-06412562) (1 mg, 4 mg, 15 mg, or 25 mg) or placebo for the next 5 visits. The randomization will assign 75% of patients to the highest dose on the last visit and 25% would receive the highest dose on one of the other four visits. Only the highest dose (25 mg) will be subject to this pseudo-randomization strategy; all other doses will be randomly distributed.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

State University of New York Stony Brook

Collaborator

Trials

1

Recruited

110+

Cerevel Therapeutics, LLC

Industry Sponsor

Trials

37

Recruited

5,500+

References

1. England pubmed.ncbi.nlm.nih.gov

Assays for enhanced activity of low efficacy partial agonists at the D(2) dopamine receptor. [2018]

2. Italy pubmed.ncbi.nlm.nih.gov

CV 205-502 treatment of macroprolactinomas. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

A novel approach to evaluate the pharmacodynamics of a selective dopamine D1/D5 receptor partial agonist (PF-06412562) in patients with stable schizophrenia. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Initial safety, tolerability pharmacodynamics, and pharmacokinetics of CI-1007 in patients with schizophrenia. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

CV 205-502--effectiveness, tolerability, and safety over 24-month study. [2019]

7. Denmark pubmed.ncbi.nlm.nih.gov

Long-term treatment of macroprolactinomas with CV 205-502. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Acute overdose of a new dopamine agonist, CV 205-502. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Specific effect of CV 205-502, a potent nonergot dopamine agonist, during a combined anterior pituitary function test. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of JX11502MA in Chinese healthy subjects: a first-in-human, randomized, double-blind, placebo-controlled study following single-dose administration. [2023]

12. England pubmed.ncbi.nlm.nih.gov

F15063, a potential antipsychotic with D2/D3 antagonist, 5-HT 1A agonist and D4 partial agonist properties. I. In vitro receptor affinity and efficacy profile. [2019]