Healthy Adults
Conditions
Keywords
probenecid, breast cancer, CDK4 inhibitor, itraconazole, PF-07220060, Drug-Drug Interaction (DDI)
Brief summary
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.
Detailed 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.
Interventions
DRUGPF-07220060
Tablet given orally
DRUGItraconazole
Capsule given orally
DRUGProbenecid
Tablet given orally
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma PF-07220060 Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 hours post PF-07220060 dose for Period 1; Pre-dose, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 and 144 hours post PF-07220060 dose for Period 2 |
| Plasma PF-07220060 Area under the plasma concentration versus time curve (AUC) | Pre-dose, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 hours post PF-07220060 dose for Period 1; Pre-dose, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 and 144 hours post PF-07220060 dose for Period 2 |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Laboratory Abnormalities | From baseline up to 28 to 35 days after last dose of investigational drug |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | From baseline up to 28 to 35 days after last dose of investigational drug |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | From baseline up to 28 to 35 days after last dose of investigational drug |
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | From baseline up to 28 to 35 days after last dose of investigational drug |
| Number of participants taking concomitant medications | From baseline up to 28 to 35 days after last dose of investigational drug |
Countries
United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed