Study to Evaluate Safety and Tolerability of Single Ascending Doses of Multiple Formulations of PF-06650833 in Healthy Subjects Under Fasted and Fed Conditions

A Phase 1, Randomized, Double Blind, Sponsor Open, Placebo Substitution, Crossover, Single Dose Escalation Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Pf 06650833 Delivered In Multiple Formulations In Healthy Subjects Under Fasted And Fed Conditions

This single ascending dose study is the first evaluation of PF-06650833 in humans. The goals are to assess the safety, tolerability and blood levels of ascending doses of multiple formulations of PF-06650833 and to perform a preliminary assessment of the effect of food on exposure, 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): 40
• 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: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female subjects of non childbearing potential between the ages of 18 and 55 years, inclusive.
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).

Exclusion Criteria:

• 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. If blood pressure (BP) is 140 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (1-1000mg) Immediate Release formulation	Drug: PF-06650833; Subjects will receive sequential single escalating doses of 1-1000 mg of Immediate Release of PF-06650833 (as solution/suspension) under fed and / or fasted conditions.; Drug: PF-06650833; Subjects will receive sequential single escalating doses of 10-500 mg of Modified Release of PF-06650833 (as capsule) under fed and / or fasted conditions.
Placebo Comparator: Immediate Release Placebo arm	Drug: Placebo; Subjects will receive sequential single escalating doses of PF-06650833 matching placebo (as solution/suspension) under fed and/ or fasted conditions.; Drug: Placebo; Subjects will receive sequential single escalating doses of PF-06650833 matching placebo (as capsule) under fed and/ or fasted conditions.
Experimental: (10-500) mg Modified Release formulation	Drug: PF-06650833; Subjects will receive sequential single escalating doses of 1-1000 mg of Immediate Release of PF-06650833 (as solution/suspension) under fed and / or fasted conditions.; Drug: PF-06650833; Subjects will receive sequential single escalating doses of 10-500 mg of Modified Release of PF-06650833 (as capsule) under fed and / or fasted conditions.
Placebo Comparator: Modified Release Placebo arm	Drug: Placebo; Subjects will receive sequential single escalating doses of PF-06650833 matching placebo (as solution/suspension) under fed and/ or fasted conditions.; Drug: Placebo; Subjects will receive sequential single escalating doses of PF-06650833 matching placebo (as capsule) under fed and/ or fasted conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment emergent adverse events and withdrawals due to treatment emergent adverse events		Baseline-5 days
Changes from baseline in vital signs ( blood pressure, pulse rate, respiratory rate and orthostatic blood pressure)		Baseline-5 days
Changes from baseline in ECG parameters (standard 12 lead ECG and telemetry)	Quantitative changes in ECG intervals	Baseline-5 days
Incidence and magnitude of treatment emergent clinical laboratory abnormalities including hematology, chemistry (including, cardiac enzymes CK, CK MB and cardiac Troponin I), serum myoglobin, urinalysis		Baseline-5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax, Tmax, AUClast, AUCinf, CL/F, Vz/F, Cmax(dn), AUCinf(dn), AUClast(dn), t½, mean residence time (MRT) for IR and MR formulations under fasted condition	Baseline-5 days
Cmax, Tmax, AUClast, AUCinf, CL/F, Vz/F, Cmax(dn), AUCinf(dn), AUClast(dn), t½, mean residence time (MRT) for IR and MR formulations under fed condition	Baseline-5 days

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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: August 21, 2014
• First Submitted That Met QC Criteria: August 21, 2014
• First Posted (Estimate): August 25, 2014

Study Record Updates

• Last Update Posted (Estimate): July 2, 2015
• Last Update Submitted That Met QC Criteria: July 1, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: B7921001; IRAK4 FIH (Other Identifier: Alias Study Number)