MK-8527 + CBZ for Healthy Subjects

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Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Anticonvulsants

Disqualifiers: Seizures, Depression, Cardiac issues, others

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

Compensation: Varies

Number of Visits: 1

16 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves healthy subjects, it is likely that participants should not be on any regular medications. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the drug MK-8527 + CBZ?

The research highlights the effectiveness of cariprazine, a component similar to MK-8527, in treating negative symptoms of schizophrenia and improving overall functioning. Cariprazine has shown benefits in treating schizophrenia and bipolar disorder, suggesting potential effectiveness for other conditions. ^{1 2 3 4 5}

Is the combination of MK-8527 and CBZ safe for humans?

Carbamazepine (CBZ) has been studied for safety in various contexts, including its use in bipolar disorder and its metabolism in healthy subjects. It was generally well-tolerated, but changes in metabolism were observed when combined with other drugs. No specific safety data for MK-8527 was found. ^{4 6 7 8 9}

What makes the drug MK-8527 + CBZ unique compared to other treatments?

The combination of MK-8527 with carbamazepine (CBZ) is unique because it involves a novel drug (MK-8527) paired with CBZ, which is commonly used for epilepsy and bipolar disorder. This combination may offer a new approach to treatment by potentially altering the metabolism of CBZ, as seen in other studies where drug interactions affect CBZ levels and efficacy. ^{6 9 10 11 12}

What is the purpose of this trial?

The goal of this study is to learn what happens to MK-8527 in a healthy person's body over time when MK-8527 is given alone and with the medication CBZ.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for healthy adults aged 18-55 who cannot have children. Participants should be in good health without any ongoing medical conditions that require treatment.

Inclusion Criteria

I am a healthy adult between 18-55 years old and cannot have children.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment A

Participants receive a single dose of MK-8527 on Day 1

1 day

1 visit (in-person)

Washout

A washout period separates Treatments A and B

1-2 weeks

Treatment B

Participants receive CBZ twice a day on Days 1 to 20 and a single dose of MK-8527 with the morning dose of CBZ on Day 14

20 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 60 days

Treatment Details

Interventions

• CBZ
• MK-8527

Trial Overview The study is testing MK-8527, a new medication, to see how it behaves in the body over time when taken alone and alongside Carbamazepine (CBZ), an existing drug.

Participant Groups

Group I: MK-8527 + CBZ Experimental Treatment 2 Interventions

Treatment A (Period 1): Participants will receive a single dose of MK-8527 on Day 1. Treatment B (Period 2): Participants will receive CBZ twice a day on Days 1 to 20 and a single dose of MK-8527 coadministered with the morning dose of CBZ on Day 14. A washout period will separate Treatments A and B.

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

Findings from Research

Cariprazine demonstrated dose-dependent efficacy in reversing core behavioral deficits associated with autism spectrum disorder (ASD) in a rat model, showing effectiveness in social play and hyperactivity.

Compared to risperidone and aripiprazole, cariprazine was uniquely effective in the social play test, suggesting it may offer a distinct therapeutic benefit for treating social communication deficits in ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder. Román, V., Adham, N., Foley, AG., et al.[2022]

Cariprazine, a D3-preferring partial agonist, has shown efficacy in treating not only the positive symptoms of schizophrenia but also negative symptoms and cognitive impairments, which are often difficult to manage with traditional antipsychotics.

In clinical trials involving both short-term and long-term studies, cariprazine was found to be generally safe and well tolerated, with no new safety concerns arising from extended use, indicating its potential as a broad-spectrum treatment for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety. Laszlovszky, I., Barabássy, Á., Németh, G.[2021]

In a pooled analysis of 1558 patients from three Phase III studies, brivaracetam (BRV) did not show a significant association between elevated carbamazepine-10,11-epoxide (CBZ-E) levels and treatment-emergent adverse events (TEAEs) or efficacy outcomes, suggesting that BRV can be safely used without adjusting the dose based on CBZ levels.

The incidence of TEAEs was similar in patients taking carbamazepine (CBZ) and those not taking it, indicating that BRV's safety profile remains consistent regardless of CBZ co-administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program. Brodie, MJ., Fakhoury, T., McDonough, B., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Remission of Persistent Negative Symptoms and Psychosocial Consequences by Combined Clozapine and Cariprazine Treatment in a Patient With Long-Standing Treatment-Resistant Schizoaffective Disorder. [2023]

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

Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Cariprazine Efficacy in Young Patients Diagnosed With Schizophrenia With Predominantly Negative Symptoms. [2021]

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

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety. [2021]

5. England pubmed.ncbi.nlm.nih.gov

The preclinical discovery and development of cariprazine for the treatment of schizophrenia. [2019]

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

Safety of carbamazepine extended-release capsules in bipolar disorder polypharmacy. [2013]

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

Single-dose kinetics and metabolism of carbamazepine-10,11-epoxide. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients. [2021]

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

Progabide-induced changes in carbamazepine metabolism. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Brivaracetam-induced elevation of carbamazepine epoxide levels: A post-hoc analysis from the clinical development program. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Free concentration of carbamazepine and carbamazepine-10,11-epoxide in children and adults. Influence of age and phenobarbitone co-medication. [2018]

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

Exposure-response analysis reveals that clinically important toxicity difference can exist between bioequivalent carbamazepine tablets. [2018]