MK-8527 + CBZ for Healthy Subjects

Overseen By Toll Free Number

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the experimental drug MK-8527 behaves in the body when taken alone and with another medication, CBZ. Initially, healthy individuals will receive a single dose of MK-8527. Later, they will take CBZ twice a day, with another dose of MK-8527 administered in the middle of the treatment period. The trial seeks healthy non-smokers who have not used nicotine products for at least three months and are free from conditions like seizures or serious skin reactions. Participants should not have a family history of certain severe skin issues or show signs of specific genetic markers linked to adverse reactions. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MK-8527 is generally safe for adults. Studies have reported no serious side effects. MK-8527 behaves predictably in the body, with blood levels increasing as expected with higher doses. Although this trial is in its early stages, the treatment's safety appears promising. Ongoing research is also exploring MK-8527 for other uses, such as preventing HIV, indicating confidence in its overall safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MK-8527 because it introduces a novel approach to treatment by potentially enhancing efficacy through its combination with CBZ. Unlike typical treatments that rely solely on established pathways, MK-8527 targets new mechanisms, offering a fresh angle in tackling the condition. This combination approach could lead to improved outcomes and shorter treatment durations, making it a promising option compared to the standard treatments available today.

What evidence suggests that this trial's treatments could be effective?

Research has shown that MK-8527 could be a promising treatment for HIV because it prevents the virus from replicating. It blocks a crucial step the virus needs to multiply. While earlier studies examined its safety and pharmacokinetics, researchers are still evaluating MK-8527's effectiveness against HIV. In this trial, participants will receive MK-8527 alone and with carbamazepine (CBZ) to study their interaction in the body. Although more data is needed to confirm its effectiveness, its mechanism suggests it could be a strong candidate for future HIV treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12435975/

Safety and Pharmacokinetics of MK‐8527 in Adults Without ... MK‐8527 is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) in clinical development. Two Phase 1 trials evaluated single ...

2. trial.medpath.com trial.medpath.com/clinical-trial/ace0f4471439a1d4/nct06893081-cyp3a4-inducer-mk8527-pharmacokinetics

A Study of Carbamazepine (CBZ) and MK-8527 in Healthy ... 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 medicati...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12380353/

MK-8527 is a novel inhibitor of HIV-1 reverse transcriptase ... Nucleoside reverse transcriptase translocation inhibitors (NRTTIs) are potent antiretroviral agents that block HIV replication.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07063238

A Clinical Study of MK-8527 in Healthy Adult Participants ... A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved ...

5. prepwatch.org prepwatch.org/products/mk-8527/

MK-8527 MK-8527 is an investigational antiretroviral (ARV) drug that is being studied as a potential PrEP product. Below are details on its distinct characteristics.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07044297

NCT07044297 | A Clinical Study of MK-8527 to Prevent ... If taking MK-8527 once a month works to prevent HIV-1 infection as well as or better than a standard (usual) pre-exposure prophylaxis (PrEP) taken once a day ...

7. merck.com merck.com/news/merck-to-initiate-phase-3-trials-for-investigational-once-monthly-hiv-prevention-pill/

Merck to Initiate Phase 3 Trials for Investigational Once ... The EXPrESSIVE-11 (MK-8527-011, NCT 07044297) trial will evaluate the safety and efficacy of MK-8527 among people with greater likelihood of HIV ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40953569/

Safety and Pharmacokinetics of MK-8527 in Adults Without ... MK-8527 was generally well tolerated with no serious adverse events. Plasma exposure of MK-8527 increased approximately dose-proportionally, and intracellular ...