MK-5720 + MK-8189 for Schizophrenia

Recruiting at 3 trial locations

Overseen By Toll Free Number

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antipsychotics

Must not be taking: Clozapine, Anticonvulsants

Disqualifiers: Seizure disorder, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

17 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests two new drugs, MK-5720 (a single muscle shot) and MK-8189 (a daily pill), in people with schizophrenia to see if they are safe and how the body handles them.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all antipsychotic medications at least 5 days or 3 half-lives (whichever is longer) before starting the treatment and during the study.

What data supports the effectiveness of the drug MK-5720 + MK-8189 for treating schizophrenia?

Research on similar drugs shows that targeting NMDA receptors and using mGluR2/3 agonists can help reverse schizophrenia-like symptoms in animal models, suggesting potential benefits for MK-5720 + MK-8189 in treating schizophrenia. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for individuals with schizophrenia or schizoaffective disorder, diagnosed at least 2 years ago. Participants must have a history of tolerating antipsychotic medications and can stop their current medication for the study duration. They cannot join if they have severe allergies, metal implants preventing MRI scans, certain infections like HIV or hepatitis, are at risk of self-harm, or have specific psychiatric exclusions.

Inclusion Criteria

I have been diagnosed with schizophrenia or schizoaffective disorder for over 2 years and need antipsychotic medication.

I have taken and tolerated antipsychotic medication for schizophrenia before.

I can stop taking my antipsychotic medication before and during the study.

Exclusion Criteria

Has a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse

I have been treated with clozapine.

Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Period 1: Oral Treatment

Participants receive once-daily oral doses of MK-8189 or placebo for 7 days

1 week

Daily visits (in-person or virtual)

Washout

A 72-hour washout period following the oral treatment phase

3 days

Period 2: Intramuscular Injection

Participants receive a single intramuscular dose of MK-5720 or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 72 days

Multiple visits (in-person or virtual) for blood sample collection

Treatment Details

Interventions

• MK-5720
• MK-8189

Trial Overview The study tests MK-5720 given as single intramuscular doses and MK-8189 taken orally once daily against placebos to assess safety and how the body processes these drugs in people with schizophrenia. The hypothesis suggests that MK-5720 will be safe and well-tolerated.

Participant Groups

Group I: Panel F Experimental Treatment 4 Interventions

Participants received 7 days of oral MK-8189 up to 48 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 560 mg or a dose matched placebo (Period 2), after a Pharmacokinetic (PK) break following Panel E.

Group II: Panel E Experimental Treatment 4 Interventions

Participants received 7 days of oral MK-8189 up to 48 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 560 mg or a dose matched placebo (Period 2).

Group III: Panel D Experimental Treatment 4 Interventions

Participants received 7 days of oral MK-8189 up to 24 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 280 mg or a dose matched placebo (Period 2).

Group IV: Panel C Experimental Treatment 4 Interventions

Participants received 7 days of oral MK-8189 up to 16 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 140 mg or a dose matched placebo (Period 2).

Group V: Panel B Experimental Treatment 4 Interventions

Participants received 7 days of oral MK-8189 8 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 70 mg or a dose matched placebo (Period 2).

Group VI: Panel A Experimental Treatment 4 Interventions

Participants received 7 days of oral MK-8189 4 mg or matched placebo treatment (Period 1), followed by a single intramuscular (IM) injection of MK-5720 35 mg or a dose matched placebo (Period 2).

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

References

1. Austria pubmed.ncbi.nlm.nih.gov

Proteome analysis after co-administration of clozapine or haloperidol to MK-801-treated rats. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Subchronic administration of LY354740 does not modify ketamine-evoked behavior and neuronal activity in rats. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Group II metabotropic glutamate receptor agonist ameliorates MK801-induced dysfunction of NMDA receptors via the Akt/GSK-3β pathway in adult rat prefrontal cortex. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits. [2020]