Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Oral Pf-06650833 In Healthy Subjects

A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Sequential Group, Multiple Ascending Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Orally Administered Pf 06650833 In Healthy Subjects

A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Controlled, Sequential Group, Multiple Ascending Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Orally Administered PF-06650833 In Healthy Subjects

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy female subjects of non childbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive.
2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
3. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
4. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. 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 at the time of dosing).
2. Any condition possibly affecting drug absorption (eg, gastrectomy).
3. A positive urine drug screen.
4. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (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 of Screening.
5. Smokers must not exceed the equivalent of 5 cigarettes per day.
6. 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).
7. Screening supine blood pressure100 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. If blood pressure (BP) is 40 mm Hg (systolic) or 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility.
8. Screening pulse or heart rate (HR) >100 bpm after at least 5 minutes of rest. If the pulse/HR is >100 bpm, the pulse/HR should be repeated two more times (separated by at least 2 minutes) and the average of the three pulse/HR values should be used to determine the subject's eligibility.
9. Screening 12 lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
10. Clinically significant abnormality on chest X ray performed at screening or within 3 months of screening date.
11. History of tuberculosis or active or latent or inadequately treated infection, positive Quantiferon TB test
12. History of hepatitis or HIV, positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HepBsAg), hepatitis B core antibodies (HepBcAb) or hepatitis C antibodies (HCVAb).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo arm	Drug: Placebo; Suspension; Drug: Placebo; Tablet (Modified Release)
Experimental: PF-06650833; Active arm , PF-06650833 kinase.	Drug: PF-06650833; Suspension; Drug: PF-06650833; Tablet (Modified Release)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of treatment emergent adverse events.	50 days
Incidence and Magnitude of Participants with Treatment-emergent hematology clinical abnormalities	50 days
Incidence and Magnitude of Participants with Treatment-emergent chemistry abnormalities (including, cardiac enzymes CK, CK-MB and cardiac Troponin-1, serum myoglobin)	50 days
Incidence and Magnitude of Participants with Treatment-emergent urinalysis abnormalities	50 Days
Changes from baseline in blood pressure	50 days
Changes from baseline in pulse rate	50 days
Changes from baseline in respiratory rate	50 days
Changes from baseline in ECG parameters (standard 12-lead ECG)	50 days
Changes from baseline in Epstein-Barr virus [EBV]	50 days
Changes from baseline in Cytomegalovirus [CMV]	50 days
Changes from baseline in Herpes simplex virus-1 and -2 [HSV-1 and HSV-2]	50 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To characterize Cmax in plasma	Day 1 and Day 14
To determine PF-06650833 excreted unchanged (AE tau and AE tau %),	Day 14
To characterize Tmax in plasma	Day 1 and Day 14
To characterize AUC tau in plasma	Day 1 and Day 14
To characterize Cmin in plasma	Day 1 and Day 14
Characterize Cmax (dose normalized) in plasma	Day 1 and Day 14
To characterize AUC tau(dose normalized) in plasma	day1 and day 14
To determine the renal clearance (CLr)	Day 14

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Danto SI, Shojaee N, Singh RSP, Li C, Gilbert SA, Manukyan Z, Kilty I. Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06650833, a selective interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, in single and multiple ascending dose randomized phase 1 studies in healthy subjects. Arthritis Res Ther. 2019 Dec 5;21(1):269. doi: 10.1186/s13075-019-2008-6.
• Winkler A, Sun W, De S, Jiao A, Sharif MN, Symanowicz PT, Athale S, Shin JH, Wang J, Jacobson BA, Ramsey SJ, Dower K, Andreyeva T, Liu H, Hegen M, Homer BL, Brodfuehrer J, Tilley M, Gilbert SA, Danto SI, Beebe JJ, Barnes BJ, Pascual V, Lin LL, Kilty I, Fleming M, Rao VR. The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial. Arthritis Rheumatol. 2021 Dec;73(12):2206-2218. doi: 10.1002/art.41953. Epub 2021 Nov 1.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: June 25, 2015
• First Posted (Estimate): June 30, 2015

Study Record Updates

• Last Update Posted (Actual): April 19, 2018
• Last Update Submitted That Met QC Criteria: April 17, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: B7921002; IRAK4 MAD (Other Identifier: Alias Study Number)