A Study to Assess Pharmacokinetics of PF-04965842 and Its Metabolites and Effect of Probenecid in Healthy Participants

Summary

A total of approximately 12 healthy male or female participants will be enrolled in the study so that at least 10 participants will complete the study. Participants will be screened within 28 days of the first dose of study medication. The single fixed-sequence will consist of 3 periods. Participants will report to the clinical research unit (CRU) at least 12 hours prior to Day 1 dosing in Period 1 and will be required to stay in the CRU for 12 days and 11 nights. Genotyping samples for cytochrome P450 (CYP) 2C19 and CYP2C9 will be collected pre dose in Period 1 only. In Period 1, participants will be administered a single oral 200 mg dose of PF-04965842 in the morning on Day 1 under fasted conditions (overnight fasting for at least 10 hours). No food will be allowed for at least 4 hours postdose and undergo serial blood sample collection for 48 hours postdose. In Period 2, participants will receive oral 200 mg dose of PF-04965842 once daily (QD) in the morning of Day 1 to Day 4 under fasted conditions (overnight fasting for at least 10 hours). No food will be allowed for at least 4 hours postdose and undergo serial blood sample collection for 48 hours postdose on Day 4. In Period 3, participants will receive probenecid 1000 mg twice daily (BID) in the mornings and evenings of Day 1 to Day 3. On the morning of Period 3 Day 2, after an overnight fast of approximately 8 hours, participants will be administered probenecid 1000 mg. A single 200 mg oral dose of PF 04965842 will be administered approximately 2 hours after the probenecid dose. Participants will remain in a fasted state for 4 hours after dosing with PF 04965842 and undergo serial blood sample collection for 48 hours post PF 04965842 dosing. Participants will be discharged from the CRU on Day 4 after all study procedures are completed. The participant will be required to have a Follow-up phone contact 28-35 days after the last dose of investigational product.

Timeline

Start

2019-05-21

Primary completion

2019-07-26

Completion

2019-07-26

Publications

• Wang X, Dowty ME, Wouters A, Tatulych S, Connell CA, Le VH, Tripathy S, O'Gorman MT, Winton JA, Yin N, Valdez H, Malhotra BK. Assessment of the Effects of Inhibition or Induction of CYP2C19 and CYP2C9 Enzymes, or Inhibition of OAT3, on the Pharmacokinetics of Abrocitinib and Its Metabolites in Healthy Individuals. Eur J Drug Metab Pharmacokinet. 2022 May;47(3):419-429. doi: 10.1007/s13318-021-00745-6. Epub 2022 Feb 28.
• Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21.

Drugs

Indications

No indication recorded.