Study to Evaluate Pharmacokinetics of A Modified Release Formulation of PF-06650833 in Healthy Subjects

A Phase 1, Open Label, Single-Dose, Within Cohort Randomized, 2-Way Crossover Study To Evaluate The Pharmacokinetics Of A Modified Release Formulation Of Pf-06650833 Under Fasting And Fed Conditions In Healthy Adult Subjects

This is a Phase 1, open-label, single-dose, within-cohort randomized, 2-way crossover study to evaluate the PK of orally administered PF-06650833 modified release tablets under fasted and high fat meal fed conditions in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833

Detailed Description

This is the third study of PF-06650833. The goals of the study are to assess the PK in healthy subjects of single doses of modified release (MR) tablets of PF-06650833 when orally administered under fasting and high fat meal fed conditions.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy female subjects of non childbearing potential and/or male subjects, between the ages of 18 and 55 years
2. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
3. Personally signed and dated Informed Consent
4. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
2. Any condition possibly affecting drug absorption
3. Positive urine drug screen.
4. Heavy smokers
5. History of regular heavy alcohol consumption within 6 months of Screening.
6. Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives
7. Screening supine blood pressure <=100 mm Hg (systolic) or<=50 mm Hg (diastolic) or>=140 mm Hg (systolic) or >=90 mm Hg (diastolic), following at least 5 minutes of supine rest.
8. Screening pulse (HR) >100 bpm after at least 5 minutes of rest.
9. Single supine 12 lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at Screening.
10. Abnormal chest X ray
11. History of TB or active or latent or inadequately treated infection, positive Quantiferon TB test.
12. History of hepatitis or positive testing for human HIV,HepBsAg, HepBc Ab or HCVAb
13. Any medical history of disease [ie, Gilbert's disease] that has the potential to cause a rise in total bilirubin over the ULN

14. Clinical laboratory abnormalities including:

    • Creatine kinase >1.2 X ULN;
    • CK MB > ULN;
    • Serum myoglobin >1.2 X ULN;
    • Cardiac Troponin I (cTn I) > ULN of the laboratory reference range;
    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) >=2 x ULN, total serum bilirubin >=1.5 mg/dL;
    • Subjects with benign ethnic neutropenia;
    • Hemoglobin <=14 gm/dl (males) and <=13 gm/dL (females).
15. Nursing female subjects; male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 28 days after the last dose of investigational product or longer based upon the compound's half life characteristics.

16. Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of investigational product until discharge from the study at the end of Period 2.

    Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of investigational product. Acetaminophen/paracetamol should not be used. As an exception, ibuprofen may be used at doses of 200 to 400 mg orally every 6 hours as needed for up to 3 of 7 consecutive days.

17. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.
18. History of sensitivity to heparin or heparin induced thrombocytopenia.
19. History of cancer (other than treated basal cell and squamous cell carcinoma of the skin) in the previous 5 years.
20. Previous exposure to PF 06650833.
21. Unwilling or unable to comply with the Lifestyle guidelines
22. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
23. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: <=400mg Modified Release Tablets, Fasted; Up to 400 mg PF-06650833 modified release tablets administered under fasted conditions	Drug: PF-06650833; Up to 400mg modified release tablets administered under fasted conditions; Drug: PF-06650833; 100mg modified release tablet administered under fasted conditions; Drug: PF-06650833; 20mg modified release tablet administered under fasted conditions; Drug: PF-06650833; Up to 400mg modified release tablets administered with high fat meal food intake; Drug: PF-06650833; 100mg modified released tablet administered with high fat meal food intake; Drug: PF-06650833; 20 mg modified release tablet administered with high fat meal food intake
Experimental: 100mg Modified Release Tablets, Fasted; 100 mg PF-06650833 modified release tablets administered under fasted conditions	Drug: PF-06650833; Up to 400mg modified release tablets administered under fasted conditions; Drug: PF-06650833; 100mg modified release tablet administered under fasted conditions; Drug: PF-06650833; 20mg modified release tablet administered under fasted conditions; Drug: PF-06650833; Up to 400mg modified release tablets administered with high fat meal food intake; Drug: PF-06650833; 100mg modified released tablet administered with high fat meal food intake; Drug: PF-06650833; 20 mg modified release tablet administered with high fat meal food intake
Experimental: 20mg Modified Release Tablets, Fasted; 20 mg PF-06650833 modified release tablets administered under fasted conditions	Drug: PF-06650833; Up to 400mg modified release tablets administered under fasted conditions; Drug: PF-06650833; 100mg modified release tablet administered under fasted conditions; Drug: PF-06650833; 20mg modified release tablet administered under fasted conditions; Drug: PF-06650833; Up to 400mg modified release tablets administered with high fat meal food intake; Drug: PF-06650833; 100mg modified released tablet administered with high fat meal food intake; Drug: PF-06650833; 20 mg modified release tablet administered with high fat meal food intake
Experimental: <= 400mg Modified Release Tablets, Fed; Up to 400 mg PF-06650833 modified release tablets administered with high fat meal food intake	Drug: PF-06650833; Up to 400mg modified release tablets administered under fasted conditions; Drug: PF-06650833; 100mg modified release tablet administered under fasted conditions; Drug: PF-06650833; 20mg modified release tablet administered under fasted conditions; Drug: PF-06650833; Up to 400mg modified release tablets administered with high fat meal food intake; Drug: PF-06650833; 100mg modified released tablet administered with high fat meal food intake; Drug: PF-06650833; 20 mg modified release tablet administered with high fat meal food intake
Experimental: 100mg Modifed Release Tablets, Fed; 100 mg PF-06650833 modified release tablets administered with high fat meal food intake	Drug: PF-06650833; Up to 400mg modified release tablets administered under fasted conditions; Drug: PF-06650833; 100mg modified release tablet administered under fasted conditions; Drug: PF-06650833; 20mg modified release tablet administered under fasted conditions; Drug: PF-06650833; Up to 400mg modified release tablets administered with high fat meal food intake; Drug: PF-06650833; 100mg modified released tablet administered with high fat meal food intake; Drug: PF-06650833; 20 mg modified release tablet administered with high fat meal food intake
Experimental: 20mg Modified Release Tablets, Fed; 20 mg PF-06650833 modified release tablets administered with high fat meal food intake	Drug: PF-06650833; Up to 400mg modified release tablets administered under fasted conditions; Drug: PF-06650833; 100mg modified release tablet administered under fasted conditions; Drug: PF-06650833; 20mg modified release tablet administered under fasted conditions; Drug: PF-06650833; Up to 400mg modified release tablets administered with high fat meal food intake; Drug: PF-06650833; 100mg modified released tablet administered with high fat meal food intake; Drug: PF-06650833; 20 mg modified release tablet administered with high fat meal food intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetic parameters of PF-06650833	Maximum plasma concentration (Cmax) of PF-06650833	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration (AUClast) of PF-06650833	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Area under the plasma concentration versus time curve from time zero extrapolated to infinite time (AUCinf) of PF-06650833 (if data permit)	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Dose-normalized maximum plasma Cmax (Cmax(dn)) of PF-06650833	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Dose-normalized area under the plasma concentration versus time curve from time zero to the time of the last quantitfiable concentration (AUClast(dn)) of PF-06650833	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833 (if data permit)	Dose-normalized area under the plasma concentration versus time curve from time zero extrapolated to infinite time (AUCinf(dn)) of PF-06650833 (if data permit)	Baseline to up to Day 14 (0 to +1) postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetic parameters of PF-06650833	Time post dose associated with the maximum plasma concentration (Tmax) of PF-06650833	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Terminal half life of PF-06650833 (if data permit)	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Lag time of plasma concentration of PF-06650833 (if data permit)	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Absorption rate constant of PF-06650833 (Ka) (if data permit)	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Apparent Clearance (CL/F) of PF-06650833 (if data permit)	Baseline to up to Day 14 (0 to +1) postdose
Plasma pharmacokinetic parameters of PF-06650833	Apparent Volume of Distribution (Vz/F) of PF-06650833 (if data permit)	Baseline for up to Day 14 (0 to +1) postdose
Treatment emergent adverse events and withdrawals	Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events	Baseline to up to Day 14 (0 to +1) postdose
Vital signs	Changes from baseline in vital signs (blood pressure, pulse rate, and respiratory rate)	Baseline to up to Day 14 (0 to +1) postdose
Electrocardiogram parameters	Changes from baseline in electrocardiogram parameters (standard 12-lead ECG)	Baseline to up to Day 14 (0 to +1) postdose
Clinical laboratory measurement	Changes from baseline in clinical laboratory values	Baseline to up to Day 14 (0 to +1) postdose

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 17, 2015
• First Posted (Estimate): November 20, 2015

Study Record Updates

• Last Update Posted (Estimate): May 9, 2016
• Last Update Submitted That Met QC Criteria: May 6, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: B7921004; IRAK4 MR PK Study (Other Identifier: Alias Study Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No