Clinical trial NCT02485769: Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Oral Pf-06650833 In Healthy Subjects
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-06-30
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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).

Primary outcomes:
measure: Incidence and severity of treatment emergent adverse events.
timeFrame: 50 days
measure: Incidence and Magnitude of Participants with Treatment-emergent hematology clinical abnormalities
timeFrame: 50 days
measure: Incidence and Magnitude of Participants with Treatment-emergent chemistry abnormalities (including, cardiac enzymes CK, CK-MB and cardiac Troponin-1, serum myoglobin)
timeFrame: 50 days
measure: Incidence and Magnitude of Participants with Treatment-emergent urinalysis abnormalities
timeFrame: 50 Days
measure: Changes from baseline in blood pressure
timeFrame: 50 days
measure: Changes from baseline in pulse rate
timeFrame: 50 days
measure: Changes from baseline in respiratory rate
timeFrame: 50 days
measure: Changes from baseline in ECG parameters (standard 12-lead ECG)
timeFrame: 50 days
measure: Changes from baseline in Epstein-Barr virus [EBV]
timeFrame: 50 days
measure: Changes from baseline in Cytomegalovirus [CMV]
timeFrame: 50 days
measure: Changes from baseline in Herpes simplex virus-1 and -2 [HSV-1 and HSV-2]
timeFrame: 50 days
Secondary outcomes:
measure: To characterize Cmax in plasma
timeFrame: Day 1 and Day 14
measure: To determine PF-06650833 excreted unchanged (AE tau and AE tau %),
timeFrame: Day 14
measure: To characterize Tmax in plasma
timeFrame: Day 1 and Day 14
measure: To characterize AUC tau in plasma
timeFrame: Day 1 and Day 14
measure: To characterize Cmin in plasma
timeFrame: Day 1 and Day 14
measure: Characterize Cmax (dose normalized) in plasma
timeFrame: Day 1 and Day 14
measure: To characterize AUC tau(dose normalized) in plasma
timeFrame: day1 and day 14
measure: To determine the renal clearance (CLr)
timeFrame: Day 14
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.