A Study to Learn About How the Study Medicines Called Itraconazole and Probenecid Change How the Body Processes PF-07220060

Pfizer

Status and phase: Enrolling; Phase 1

Conditions: Healthy Adults

Treatments: Drug: Itraconazole; Drug: PF-07220060; Drug: Probenecid

Study type: Interventional

Funder types: Industry

Identifiers

NCT07160738

C4391011

Details and patient eligibility

About

The purpose of the study is to see and learn the effect of multiple doses of a strong CYP3A4 inhibitor and a potent UGT2B7 inhibitor on the PK of PF-07220060.

Full description

This study is seeking participants who are:

1. male and female aged 18 to 65 years and are healthy as confirmed by medical tests 2. with body mass index (BMI) of 17.5-30.5 kilogram per meter squared (kg/m2); and a total body weight of more than 50 kilograms (110 pounds).

The study will consist of 2 groups each containing 2 periods. In both groups, participants will receive a single dose of PF-07220060 in Period 1. In group 1 Period 2, itraconazole will be given once a day from Day 1 to Day 9. On the morning of Period 2 Day 4, a single dose of PF 07220060 will be taken by mouth immediately after itraconazole is taken by mouth. In group 2 Period 2, probenecid will be given 4 times a day from Day 1 to Day 9. On the morning of Period 2 Day 3, a single dose of PF 07220060 will be taken by mouth, immediately after probenecid is taken by mouth.

In both groups, PF-07220060 will be given by mouth about 30 minutes after a moderate fat standard calorie meal in Period 1. In cohort 1 Period 2, itraconazole will be given by mouth once a day from Day 1 to Day 9 about 30 minutes after a moderate fat standard calorie meal. On the morning of Period 2 Day 4, a single dose of PF 07220060 will be administered by mouth immediately after itraconazole administration. In cohort 2 Period 2, probenecid will be given by mouth 4 times a day (QID) with 6±2 hours intervals from Day 1 to Day 9 with or without food. On Period 2 Day 2, the last probenecid dose prior to the Day 3 first dose will be given under fasted condition. On the morning of Period 2 Day 3, after 10 hours fasting, ~30 min after a moderate fat standard calorie breakfast, a single dose of PF-07220060 will be administered by mouth, immediately after probenecid administration.

The study will look at the effect of multiple doses of itraconazole and probenecid on how the body processes a single oral dose of PF-07220060.

Participants will take part in this study for up to 78 days for group 1 and 77 days for group 2. Following period 1 and 2, they will undergo lab tests and blood samples will be collected after administration of PF-07220060. Participants will be discharged from the research unit at the end of period 2 following completion of all tests.

Enrollment: 28 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion

• Healthy volunteers who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.
• Body mass index (BMI) of 17.5-30.5 kg/m2; and a total body weight >50 kg (110 lb).
• Evidence of a personally signed and dated Informed Consent Document (ICD) indicating that the participant has been informed of all pertinent aspects of the study.

Exclusion

• Evidence or history of blood dyscrasias, uric acid kidney stones, peptic ulcer or gout for probenecid cohort (Applicable to Cohort 2).
• Evidence or history of genetic deficiency of glucose -6- phosphate dehydrogenase in red blood cells for probenecid cohort (Applicable to Cohort 2).
• Concomitant use of any medications or substances that are strong inducers or inhibitors of CYP3A4 or UGT2B7 are prohibited within 5 half-lives plus 14 days (up to 28 days) prior to first dose of PF 07220060.
• Concomitant use of methotrexate, salicylates, penicillin or other beta-lactams, sulfonamide, ketamine, thiopental anesthesia, indomethacin, naproxen, ketoprofen, meclofenamate, lorazepam are prohibited within 5 half-lives plus 14 days (up to 28 days) prior to first dose of PF 07220060 (Applicable to Cohort 2).
• History of sensitivity to azole antifungals, probenecid, or any of the formulation components of PF-07220060.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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28 participants in 4 patient groups

Cohort 1, Period 1: PF-07220060

Experimental group

Description:

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

Treatment:

Drug: PF-07220060

Cohort 1, Period 2: PF-07220060 and itraconazole

Experimental group

Description:

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

Treatment:

Drug: PF-07220060

Drug: Itraconazole

Cohort 2, Period 1: PF-07220060

Experimental group

Description:

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

Treatment:

Drug: PF-07220060

Cohort 2, Period 2: PF-07220060 probenecid

Experimental group

Description:

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.

Treatment:

Drug: Probenecid

Drug: PF-07220060