Drug Interaction Study in Healthy Subjects

No longer recruiting at 1 trial location

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must be taking: Carbamazepine

Disqualifiers: Hypertension, Renal disease, Cardiac, others

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

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the interaction between ibuzatrelvir, a medication, and carbamazepine, a drug known to affect the processing of other drugs in the body. Healthy participants will first take ibuzatrelvir alone, followed by a combination with carbamazepine, to observe any changes in drug processing. Ideal participants are healthy individuals without ongoing health issues. Participants will stay at the study clinic for 18 days for monitoring and testing. As a Phase 1 trial, this research focuses on understanding how ibuzatrelvir works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, your medical history and current medications will be reviewed during the screening period to determine eligibility.

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

Research has shown that ibuzatrelvir, a new medication under study, carries a low risk of safety concerns based on earlier research. This indicates it was generally well-tolerated by participants in previous studies. Researchers are also testing its ability to reduce the amount of virus in the body.

Carbamazepine, the other drug in the study, has already received approval for treating other conditions, indicating its known safety profile, though every drug can have some side effects.

The current study is in an early phase, primarily focusing on assessing the safety of these drugs, especially when taken together. Participants in this study will be closely monitored by doctors for any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ibuzatrelvir because it offers a potential new approach to managing conditions that involve complex drug interactions. Unlike standard treatments that often require careful balancing to avoid interactions, ibuzatrelvir is being studied for its ability to be safely combined with other medications like carbamazepine. This could simplify treatment regimens and enhance patient safety. Additionally, ibuzatrelvir's novel mechanism of action might provide benefits that current options do not, offering new hope for more effective management of these conditions.

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

Research shows that ibuzatrelvir offers promising antiviral effects against the virus causing COVID-19. Studies have found it safe and well-tolerated, with the potential to prevent the worsening of COVID-19, including reducing hospital visits and severe outcomes. In this trial, one treatment arm will administer ibuzatrelvir alone. Another treatment arm will combine ibuzatrelvir with carbamazepine, known to increase the activity of the liver enzyme CYP3A4. This study examines how carbamazepine might alter ibuzatrelvir's effects, which is crucial for understanding its effectiveness and safety. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for healthy adults who are not able to have children. Participants must be at least 18 years old and will undergo a screening process to confirm their health status before joining the study. They'll need to stay in the clinic for 18 days.

Inclusion Criteria

I am healthy with normal medical exams, lab tests, blood pressure, pulse, and ECG results.

Exclusion Criteria

I don't have any serious ongoing health issues apart from untreated seasonal allergies.

Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

Participants with ANY of the following abnormalities in clinical laboratory tests at screening and prior to dosing in each period, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: ALT, AST, Bilirubin ≥1.5 x ULN. Participants with an elevated total bilirubin consistent with Gilberts Disease may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 28 days

Treatment Period 1

Participants receive a single oral dose of ibuzatrelvir 600 mg

1 day

1 visit (in-clinic)

Treatment Period 2

Participants receive carbamazepine BID titrated from 100 mg to 300 mg over 15 days with a single ibuzatrelvir 600 mg dose coadministered on day 15

15 days

In-clinic stay for 18 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 to 35 days post-discharge

1 visit (in-person or telephone)

What Are the Treatments Tested in This Trial?

Interventions

• Carbamazepine
• Ibuzatrelvir

Trial Overview

The study tests how carbamazepine, which affects drug processing in the body, influences ibuzatrelvir levels. It involves two treatments: one with just ibuzatrelvir and another combining it with gradually increased doses of carbamazepine.

How Is the Trial Designed?

Group I: Period 2 Experimental Treatment 2 Interventions

carbamazepine BID oral doses on Day 1-15. ibuzatrelvir single oral dose on Day 14.

Group II: Period 1 Experimental Treatment 1 Intervention

ibuzatrelvir single oral dose on Day 1.

Carbamazepine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Tegretol for:

• Seizure disorders
• Trigeminal neuralgia
• Bipolar disorder

Approved in European Union as Carbamazepine for:

• Epilepsy
• Trigeminal neuralgia
• Mania associated with bipolar disorder

Approved in Canada as Tegretol for:

• Seizure disorders
• Trigeminal neuralgia
• Bipolar disorder

Approved in Japan as Carbamazepine for:

• Epilepsy
• Trigeminal neuralgia
• Mania associated with bipolar disorder

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

A patient taking high doses of carbamazepine for epilepsy experienced neurotoxicity after being prescribed erythromycin and ketoconazole, highlighting a dangerous drug interaction.

This case emphasizes the need for careful monitoring and communication among healthcare providers to prevent adverse effects from drug interactions across different medical specialties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple drug interaction across medical specializations. Andrade, C.[2021]

The concurrent administration of ritonavir (RTV) and carbamazepine (CBZ) in a patient with HIV and epilepsy led to dangerously elevated levels of CBZ, resulting in symptoms like vomiting, vertigo, and liver dysfunction.

Discontinuing RTV and adjusting the CBZ dosage successfully normalized CBZ levels and resolved the adverse symptoms, highlighting the importance of monitoring drug interactions, especially since RTV inhibits the liver enzymes that metabolize CBZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential interaction between ritonavir and carbamazepine. Kato, Y., Fujii, T., Mizoguchi, N., et al.[2019]

CYP3A4 inhibitors, such as itraconazole and grapefruit juice, can significantly alter the metabolism of various medications, leading to potentially dangerous interactions like torsades de pointes when combined with certain drugs like terfenadine or cisapride.

While many interactions can lead to adverse effects, some can be beneficial, such as using CYP3A4 inhibitors to enhance the effectiveness of drugs like cyclosporin, highlighting the importance of understanding individual patient factors in managing drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Dresser, GK., Spence, JD., Bailey, DG.[2022]

In a study involving 7 healthy epileptic patients, cimetidine did not significantly affect the plasma levels of carbamazepine (CBZ) or its metabolite, indicating no interaction between the two drugs.

The study lasted for 7 days, and the results suggest that cimetidine can be safely administered alongside carbamazepine without altering its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of interaction between cimetidine and carbamazepine. Sonne, J., Lühdorf, K., Larsen, NE., et al.[2019]

Coadministration of efavirenz and carbamazepine in healthy adults significantly reduced the exposure of both drugs, indicating a pharmacokinetic interaction that could affect their effectiveness.

Specifically, efavirenz exposure decreased by about 36% and carbamazepine exposure decreased by about 27%, while the metabolite carbamazepine-10,11-epoxide showed minimal change, suggesting that careful monitoring may be needed when these medications are used together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic interaction between efavirenz and carbamazepine after multiple-dose administration in healthy subjects. Ji, P., Damle, B., Xie, J., et al.[2020]

In a study involving 40 epileptic patients, both the generic carbamazepine product Epitol and the brand name Tegretol showed equivalent clinical efficacy and bioequivalency, indicating that Epitol can be a suitable alternative to Tegretol.

The average seizure frequencies were statistically similar between the two products, with Epitol showing a slightly earlier time to peak effect, suggesting it may have a faster onset of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic bioequivalency study of brand name versus generic carbamazepine. Oles, KS., Penry, JK., Smith, LD., et al.[2019]

A study involving 15 healthy adults showed that both Carbatrol and Tegretol-XR have similar pharmacokinetic profiles for carbamazepine (CBZ) and its metabolite, CBZ-10, 11-epoxide (CBZ-E), after 5 days of dosing, indicating comparable efficacy and safety.

The research revealed a unique sigmoidal shape in the plasma concentration profiles of CBZ-E, suggesting that autoinduction may occur by the fifth day of dosing, which could influence the drug's effectiveness over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reanalysis of carbamazepine and carbamazepine-epoxide pharmacokinetics after multiple dosing of extended release formulation. Konsil, J., Dechasathian, S., Mason, DH., et al.[2015]

A study involving 12 healthy volunteers found that both controlled release formulations of carbamazepine (CBZ) are bioequivalent, meaning they release the drug into the bloodstream at similar rates and amounts, with formulation A showing slightly higher efficacy than formulation B.

Both controlled release formulations resulted in lower peak drug concentrations (Cmax) and area under the curve (AUC) compared to the conventional formulation, indicating a smoother release of the medication over time and less fluctuation in plasma levels, which is beneficial for maintaining stable drug levels in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative bioavailability study of a conventional and two controlled release oral formulations of Tegretol (carbamazepine)--200 mg. Revankar, SN., Bhatt, AD., Desai, ND., et al.[2013]

Two cases of carbamazepine toxicity were reported in 6-year-old children after substituting Tegretol with Epitol, leading to significant increases in serum carbamazepine levels (22% and 41%).

Both children became asymptomatic after their serum concentrations were reduced, indicating that while the substitution can lead to toxicity, it is manageable with appropriate medical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbamazepine toxicity resulting from generic substitution. Gilman, JT., Alvarez, LA., Duchowny, M.[2019]

Carbamazepine (CBZ) can significantly affect the metabolism of other drugs, potentially leading to clinically important drug interactions, as it may accelerate the metabolism of medications like phenytoin and warfarin.

Conversely, other drugs such as phenytoin and erythromycin can also influence the metabolism of CBZ, highlighting the need for careful monitoring of drug interactions in patients taking CBZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbamazepine drug interactions. Baciewicz, AM.[2019]

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The present study will examine whether there is a medically important drug interaction between St. John's wort and Tegretol when Tegretol is taken for 1 day.

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Statistical analysis showed a significant decrease in C0/D CBZ ratio between G1 receiving CBZ alone and G2 receiving CBZ and enzyme inducers antiepileptic drugs ...

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After an oral dose of radiolabeled carbamazepine, 72% of the administered radioactive dose was detected in the urine and the remainder of the ingested dose was ...

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sciencedirect.com/science/article/pii/S0022354915507260

Controlled, multidose, pharmacokinetic evaluation of two ...

In this randomized, crossover study, 15 normal healthy adults received 400 mg of each formulation b.i.d. for 5 days. Blood samples for CBZ and CBZ-E analysis ...

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frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1542063/full

Effect of the frequently used antiepileptic drugs ...

In our trial, the range of exposure changes caused by carbamazepine was 3.1-fold between individuals, ranging from minor exposure decreases to ...

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NCT06646042 | A Study to Learn If the Study Medicine ...

The purpose of this study is to estimate the effect of carbamazepine, a strong CYP3A4 inducer, on the pharmacokinetics (PK) of ibuzatrelvir in healthy ...

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withpower.com

withpower.com/trial/phase-1-healthy-subjects-hs-10-2024-ee476

Drug Interaction Study in Healthy Subjects

This Phase 1 medical study run by Pfizer needs participants to evaluate whether Carbamazepine and Ibuzatrelvir will have tolerable side effects & efficacy ...

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A Study to Learn If the Study Medicine Called Carbamazepine Changes How the Body Processes the Other Study Medicine Ibuzatrelvir in Healthy Adults.

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Online Trial Tracker

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... ibuzatrelvir were evaluated to assess potential for 3A-mediated drug-drug interaction (DDI) of ibuzatrelvir. Description of Methods and ...