Drug Interaction Study Evaluating the Effect of Rifampin on PK and Safety of PF 04965842.

NCT03637790 | Completed Phase 1 FDA Drug

• 2 other identifiers: B74510192018-002167-25
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 open label, 2 period, single fixed sequence study designed to evaluate the effect of repeat dose oral rifampin on single dose PF 04965842 PK after a single 200 mg oral dose in healthy subjects. A total of 12 healthy male and/or female subjects will be enrolled in the study so that at least 10 subjects will complete the study. Subject 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 11 days and 10 nights. Genotyping samples for CYP2C19 and CYP2C9 will be collected predose in Period 1 only. In Period 1, subjects will be administered a single oral 200 mg dose of PF 04965842 in the morning on Day 1 under fasted conditions. No food will be allowed for at least 4 hours postdose and undergo serial blood sample collection for 24 hours postdose to characterize the PK profile of PF 04965842. In Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842. Subjects will remain in a fasted state for 4 hours after dosing with PF 04965842 and undergo serial blood sample collection for 24 hours post PF 04965842 dosing to characterize the PK profile of PF 04965842. Subjects will be discharged from the CRU on Day 9 of Period 2 after all study procedures are completed. The subject will be required to return to the CRU for on site follow up visits 7 14 days, and have a follow up phone contact 28 35 days after the last dose of PF 04965842.

Conditions

Healthy

Keywords

healthy volunteers

Outcome Measures

Primary Outcomes (2)

• Plasma PF 04965842 Cmax PK

  Maximum observed plasma concentration for PF 04965842

  Day 1 on period 1 and Days 1, 8 and 9 on period 2

• AUCinf for PF 04965842

  Area under the curve from time zero to extrapolated infinite time tor PF 04965842

  Day 1 on period 1 and Days 1, 8 and 9 on period 2

Secondary Outcomes (4)

• Number of subjects with adverse events (AEs).

  Screening up to 28-35 days after the last dose of PF 04965842 in period 2

• Number of subjects with laboratory tests findings of potential clinical importance

  Screening up to 7-14 days after the last dose of PF 04965842 in period 2

• Number of subjects with clinically significant abnormal vital signs

  Screening up to 7-14 days after the last dose of PF 04965842 in period 2

• Number of subjects with clinically significant abnormal Electrocardiograms (ECGs)

  Screening up to 7-14 days after the last dose of PF 04956842 in period 2.

Study Arms (2)

PF 04965842

OTHER

In Period 1, subjects will be administered a single oral 200 mg dose of PF 04965842 in the morning on Day 1 under fasted conditions.

Drug: PF-04965842

Rifampin and PF 04965842

OTHER

In Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842.

Drug: PF-04965842; Other: rifampin

Interventions

PF-04965842 DRUG

single oral 200 mg dose of PF 04965842 in the morning on Day 1 under fasted conditions.In Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842.

PF 04965842; Rifampin and PF 04965842

rifampin OTHER

In Period 2, subjects will receive rifampin 600 mg QD in the mornings of Day 1 to Day 7, approximately 1 hour before the morning meal. On the morning of Day 8, after an overnight fast of approximately 9 hours, subjects will be administered rifampin 600 mg 1 hour prior to administration of a single 200 mg oral dose of PF 04965842

Rifampin and PF 04965842

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy female subjects and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate measurement, 12 lead ECG, or clinical laboratory tests.
• Female subjects of non childbearing potential must meet at least 1 of the following criteria:
• Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight \>50 kg (110 lb).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Subjects with any of the following characteristics/conditions will not be included in the study:
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Evidence of acute exacerbation of dermatological condition (eg, AD, eczema or psoriasis) or visible rash present during physical examination. Subjects with history of psoriasis, AD or eczema can be included in the study.
• Subjects, who according to the product label for rifampin, would be at increased risk if dosed with rifampin.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug test.
• History of regular alcohol consumption exceeding 14 drinks/week for female subjects or 21 drinks/week for male subjects (1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 6 months before screening.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer).
• Screening supine systolic BP \<90 mm Hg or \>140 mm Hg following at least 5 minutes of supine rest OR Screening supine diastolic BP \<50 mm Hg or \>90 mm Hg following at least 5 minutes of supine rest.
• If a subject meets any of these criteria, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the subject's eligibility.
• Screening supine 12 lead ECG demonstrating a corrected QT (QTc) interval \>450 msec or a QRS interval \>120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the subject's eligibility.
• Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use 1 highly effective method of contraception as outlined in this protocol Contraception section for the duration of the study and for at least 28 days after the last dose of investigational product.
• Subjects with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 1.5 × upper limit of normal (ULN);
• Total bilirubin level 1 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ULN.
• Use of CYP2C19 inhibitors (eg, fluconazole, fluoxetine, fluvoxamine, ticlopidine omeprazole, voriconazole, cimetidine, esomeprazole, and felbamate) or inducers (eg, rifampin, ritonavir, efavirenz, enzalutamide, phenytoin, and St. John's Wort) within 28 days or 5 half lives (whichever is longer) prior to dosing.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Location

Related Publications (2)

• 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.

  PMID: 35226304 DERIVED

• 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.

  PMID: 35061234 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

abrocitinib; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2018
• First Posted: August 20, 2018
• Study Start: September 13, 2018
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: February 28, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)