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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02609139
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 6
• Duration (Months): 3
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833; Drug: PF-06650833	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

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
Experimental: 100mg Modified Release Tablets, Fasted 100 mg PF-06650833 modified release tablets administered under fasted conditions	Drug: PF-06650833; 100mg modified release tablet administered under fasted conditions
Experimental: 20mg Modified Release Tablets, Fasted 20 mg PF-06650833 modified release tablets administered under fasted conditions	Drug: PF-06650833; 20mg modified release tablet administered under fasted conditions
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 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; 100mg modified released 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; 20 mg modified release tablet administered with high fat meal food intake

Outcome Measures

Primary Outcome Measures

1. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Maximum plasma concentration (Cmax) of PF-06650833

2. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration (AUClast) of PF-06650833

3. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Area under the plasma concentration versus time curve from time zero extrapolated to infinite time (AUCinf) of PF-06650833 (if data permit)

4. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Dose-normalized maximum plasma Cmax (Cmax(dn)) of PF-06650833

5. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   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

6. Plasma pharmacokinetic parameters of PF-06650833 (if data permit) [Baseline to up to Day 14 (0 to +1) postdose]

   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)

Secondary Outcome Measures

1. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Time post dose associated with the maximum plasma concentration (Tmax) of PF-06650833

2. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Terminal half life of PF-06650833 (if data permit)

3. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Lag time of plasma concentration of PF-06650833 (if data permit)

4. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Absorption rate constant of PF-06650833 (Ka) (if data permit)

5. Plasma pharmacokinetic parameters of PF-06650833 [Baseline to up to Day 14 (0 to +1) postdose]

   Apparent Clearance (CL/F) of PF-06650833 (if data permit)

6. Plasma pharmacokinetic parameters of PF-06650833 [Baseline for up to Day 14 (0 to +1) postdose]

   Apparent Volume of Distribution (Vz/F) of PF-06650833 (if data permit)

7. Treatment emergent adverse events and withdrawals [Baseline to up to Day 14 (0 to +1) postdose]

   Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events

8. Vital signs [Baseline to up to Day 14 (0 to +1) postdose]

   Changes from baseline in vital signs (blood pressure, pulse rate, and respiratory rate)

9. Electrocardiogram parameters [Baseline to up to Day 14 (0 to +1) postdose]

   Changes from baseline in electrocardiogram parameters (standard 12-lead ECG)

10. Clinical laboratory measurement [Baseline to up to Day 14 (0 to +1) postdose]

    Changes from baseline in clinical laboratory values

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

1. 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.

2. 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.

1. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.

2. History of sensitivity to heparin or heparin induced thrombocytopenia.

3. History of cancer (other than treated basal cell and squamous cell carcinoma of the skin) in the previous 5 years.

4. Previous exposure to PF 06650833.

5. Unwilling or unable to comply with the Lifestyle guidelines

6. 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.

7. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Haven Clinical Research Unit	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02609139
• Other Study ID Numbers: B7921004; IRAK4 MR PK Study
• First Posted: Nov 20, 2015
• Last Update Posted: May 9, 2016
• Last Verified: May 1, 2016

Study Results

No Results Posted as of May 9, 2016