Itraconazole + Probenecid for Healthy Adults

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: CYP3A4 inhibitors, UGT2B7 inhibitors

Disqualifiers: Blood dyscrasias, G6PD deficiency, others

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

Compensation: Varies

Number of Visits: 1

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two medications, itraconazole (an antifungal drug) and probenecid (a gout treatment), affect the body when combined with a new drug, PF-07220060. The goal is to understand their interactions, specifically how the body processes the new drug. Participants will be divided into groups to receive different treatment combinations over a short period. This trial targets healthy adults with no major health issues who aren't taking certain medications. As a Phase 1 trial, this research aims to understand 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?

You may need to stop taking certain medications before joining the trial, especially if they strongly affect specific enzymes in your body. Some drugs, like methotrexate and certain pain relievers, must be stopped up to 28 days before starting the trial.

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

Research has shown that itraconazole is generally safe for people. In studies with 602 patients, it was well-tolerated, even by those with serious fungal infections. Some individuals might experience side effects like nausea or headache, and there have been rare reports of heart issues, but these are uncommon.

Probenecid has long been used to treat gout and is considered safe for most people. Side effects can include mild stomach upset and headache, but serious side effects are rare.

Since both itraconazole and probenecid are already approved for other uses, they are generally considered safe. However, this is an early-phase trial, so not all possible side effects may be known yet. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine itraconazole and probenecid, which could offer a unique approach to enhancing drug absorption and effectiveness. Unlike standard treatments that might rely on singular mechanisms, this combo uses itraconazole, an antifungal that can also inhibit certain enzymes, potentially boosting the effectiveness of other drugs. Probenecid, typically used to prolong the action of certain antibiotics, might increase the duration and intensity of itraconazole's effects. This innovative pairing could lead to more effective treatments by optimizing how drugs are processed in the body, offering a fresh strategy in drug therapy.

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

This trial will compare the effects of itraconazole and probenecid in healthy adults. Research has shown that itraconazole effectively treats fungal infections, with about 58% of patients cured in some studies. It helps patients feel better and live longer in various conditions. Probenecid has been moderately successful in managing gout and can help the body clear viruses faster. It also stops viruses from multiplying, as demonstrated in studies with cells and animals. Both itraconazole and probenecid have shown promising results in their specific uses, suggesting potential benefits in this study. ^{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 with a BMI of 17.5-30.5 kg/m2 and weight over 50 kg, who haven't used strong CYP3A4 or UGT2B7 inducers/inhibitors recently. People with blood disorders, uric acid kidney stones, peptic ulcer, gout, glucose-6-phosphate dehydrogenase deficiency or sensitivity to the study drugs can't join.

Inclusion Criteria

I meet the specific requirements to participate.

My BMI is between 17.5 and 30.5, and I weigh more than 110 lbs.

I have signed and understand the informed consent document for this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive a single dose of PF-07220060 administered with food

1 day

1 visit (in-person)

Treatment Period 2 - Cohort 1

Participants receive itraconazole once daily from Day 1 to Day 9, with a single dose of PF-07220060 on Day 4

9 days

Daily visits (in-person)

Treatment Period 2 - Cohort 2

Participants receive probenecid four times a day from Day 1 to Day 9, with a single dose of PF-07220060 on Day 3

9 days

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including lab tests and blood samples

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Itraconazole
• Probenecid

Trial Overview The study tests how Itraconazole (a strong CYP3A4 inhibitor) and Probenecid (a potent UGT2B7 inhibitor) affect the body's processing of PF-07220060 in healthy individuals.

How Is the Trial Designed?

Group I: Cohort 2, Period 2: PF-07220060 probenecid Experimental Treatment 2 Interventions

In Cohort 2, Period 2, participants will receive oral dose of probenecid four times a day from Day 1 to Day 9. On the morning of Day 3, participants will first receive one oral dose of probenecid followed by a single oral dose of PF-07220060 tablet.

Group II: Cohort 2, Period 1: PF-07220060 Experimental Treatment 1 Intervention

In Cohort 2, Period 1 participants will receive a single dose of PF-07220060 tablet given orally and administered with food on Day 1.

Group III: Cohort 1, Period 2: PF-07220060 and itraconazole Experimental Treatment 2 Interventions

In Cohort 1 Period 2, participants will receive oral dose of itraconazole once daily from Day 1 to Day 9. On the morning of Day 4, participants will first receive one oral dose of itraconazole followed by a single oral dose of PF-07220060 tablet

Group IV: Cohort 1, Period 1: PF-07220060 Experimental Treatment 1 Intervention

In Cohort 1, Period 1 participants will receive a single dose of PF-07220060 tablet given orally and administered with food on Day 1.

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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10520254/

Efficacy of Super-Bioavailable Itraconazole and Conventional ... At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/ ...

2. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2795924

Effect of Different Itraconazole Dosing Regimens in Adult ... Itraconazole is highly efficacious at all 3 doses but requires prolonged treatment, and a substantial number of patients relapsed after successful treatment.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03920527

Six Months Versus 12 Months of Oral Itraconazole Therapy ... In this randomized controlled trial, we compare the clinical outcomes of six months versus twelve months of itraconazole therapy in treatment naïve subjects ...

4. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/itraconazole

Itraconazole - an overview Itraconazole is effective for juvenile and adult specimens of several ... Currently, itraconazole has prolonged patient survival and improved patient outcomes in ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa021931

Itraconazole to Prevent Fungal Infections in Chronic ... The elimination half-life of itraconazole in healthy adult volunteers is approximately 20 hours after a single dose and 30 hours after multiple doses.

6. mayoclinic.org mayoclinic.org/drugs-supplements/itraconazole-oral-route/description/drg-20071421

Itraconazole (oral route) - Side effects & dosage Adults—200 milligrams (mg) once a day for 12 weeks in a row. Children—Use and dose must be determined by your doctor. For oral dosage form ( ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/020083s062lbl.pdf

SPORANOX® (itraconazole) Capsules - accessdata.fda.gov Overall exposure to itraconazole, based on AUC, was decreased in patients with moderate and severe renal impairment by approximately 30% and 40%, respectively, ...

8. drugs.com drugs.com/mtm/itraconazole.html

Itraconazole Uses, Side Effects & Warnings Itraconazole is an antifungal medication that is used in adults to treat infections caused by fungus. This includes infections in any part of the body.

9. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Itraconazole

Itraconazole | C35H38Cl2N8O4 | CID 55283 - PubChem While itraconazole is a relatively safe medication, there are some adverse side effects with itraconazole use. Cardiotoxicity is a rare adverse effect.

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/208901s004lbl.pdf

HIGHLIGHTS OF PRESCRIBING INFO - accessdata.fda.gov Safety data with itraconazole capsules were derived from 602 patients treated for systemic fungal disease in U.S. clinical trials who were immunocompromised ...