Absorption, Metabolism, Excretion and Absolute Bioavailability

NCT03250039 | Completed Phase 1

• 2 other identifiers: B74510082017-000461-73
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

This study will investigate the absorption, metabolism and excretion of 14C-PF 04965842 and characterize plasma, fecal and urinary radioactivity and identify any metabolites, if possible, of 14C PF-04965842 in humans. In addition, this study will provide a better understanding of the pharmacokinetic disposition of PF-04965842 by obtaining intravenous (IV) clearance and delineating the extent of oral absorption (absolute bioavailability (F) and fraction absorbed (Fa)).

Conditions

Healthy

Keywords

Absorption, Metabolism, Excretion, Absolute Bioavailability

Outcome Measures

Primary Outcomes (1)

• Cumulative recovery of radioactivity

  Total radioactivity in urine and feces based on total administered dose.

  From predose to Day 14 day

Secondary Outcomes (11)

• Cmax

  From predose to Day 5

• Tmax

  From predose to Day 5

• AUClast

  From predose to Day 5

• AUCinf

  From predose to Day 5

• t1/2

  From predose to Day 5

Study Arms (2)

Mass Balance

EXPERIMENTAL

Cumulative recovery of radioactivity in urine and feces

Drug: PF-04965842

Absolute Bioavailability

EXPERIMENTAL

Oral absolute bioavailability

Drug: Absolute Bioavailability

Interventions

PF-04965842 DRUG

14C labeled PF-04965842

Mass Balance

Absolute Bioavailability DRUG

Oral dose of unlabeled PF-04965842 and an IV dose of 14C labeled PF- 04965842

Absolute Bioavailability

Eligibility Criteria

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

You may qualify if:

• Healthy 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 and pulse rate measurement, 12 lead electrocardiogram (ECG), or clinical laboratory tests.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).
• 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 study confinement period, scheduled visits, treatment plan, laboratory tests, contraceptive requirements 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, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies).
• Any clinically significant malabsorption condition (eg, gastrectomy, bowel resection).
• A positive urine drug screen for drugs of abuse or recreational drugs.
• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb).
• History of abuse of alcohol or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 or more alcoholic drinks (male) in about 2 hours. As a general rule, alcohol intake should not exceed 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
• Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.
• Treatment with an investigational drug within 60 days.
• Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.
• Screening supine blood pressure \>=140 mm Hg (systolic) or \>=90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure is \>=140 mm Hg (systolic) or \>=90 mm Hg (diastolic), the blood pressure measurement should be repeated two more times and the average of the three measurements should be used to assess the subject's eligibility.
• Supine 12 lead ECG demonstrating QTcF \>450 msec or a QRS interval \>120 msec at screening. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTcF or QRS values should be used to determine the subject's eligibility.
• Use of prescription or nonprescription drugs (including vitamins and dietary supplements) within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. As an exception, acetaminophen may be used at doses of =\<1 g/day. Limited use of non prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case by case basis following approval by Pfizer.
• Use of herbal supplements within 28 days prior to the first dose of study medication.
• Blood donation (excluding plasma donations) of no more than 100 mL or more within 56 days prior to dosing.
• An estimated glomerular filtration rate of \<90 mL/min/1.73 m2 based on the four variable Modification of Diet in Renal Disease (MDRD) equation.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

PRA Health Sciences

Groningen, 9713 GZ, Netherlands

Location

PRA Health Sciences

Groningen, 9728 NZ, Netherlands

Location

Related Publications (1)

• Bauman JN, Doran AC, King-Ahmad A, Sharma R, Walker GS, Lin J, Lin TH, Telliez JB, Tripathy S, Goosen TC, Banfield C, Malhotra BK, Dowty ME. The Pharmacokinetics, Metabolism, and Clearance Mechanisms of Abrocitinib, a Selective Janus Kinase Inhibitor, in Humans. Drug Metab Dispos. 2022 Aug;50(8):1106-1118. doi: 10.1124/dmd.122.000829. Epub 2022 Jun 14.

  PMID: 35701182 DERIVED

Related Links

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

MeSH Terms

Interventions

abrocitinib

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will be an open label, non randomized, 2 period, fixed sequence, single dose study to characterize the absorption, metabolism and excretion of 14C- PF-04965842 and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-04965842 following oral administration of unlabeled PF-04965842 and IV and oral administration of 14C-PF-04965842 to healthy male subjects.

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: August 15, 2017
• Study Start: July 10, 2017
• Primary Completion: September 15, 2017
• Study Completion: September 15, 2017
• Last Updated: December 21, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)