A Study In Healthy People To Evaluate Safety, Toleration, Pharmacokinetics And Pharmacodynamics Of Multiple Oral Doses Of PF-06743649

A Phase 1 Double Blind (3rd Party Open) Randomized, Placebo Controlled, Dose Escalation Study To Investigate The Safety,Tolerability, Pharmacokinetics And Pharmacodynamics Of Repeat Doses Of Pf-06743649 With Or Without Food In Healthy Adult Subjects

The purpose of this study in healthy people is to evaluate safety, toleration and time course of plasma concentration of multiple oral doses of PF-06743649. The pharmacodynamic activity of PF-06743649 will also be assessed. The effect of food on PK of PF-06743649 will also be investigated.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06743649; Drug: Placebo; Drug: PF-06743649; Drug: Placebo; Drug: PF-06743649; Drug: PF-06743649; Drug: Placebo; Drug: PF-06743649; 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: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
• Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

Exclusion Criteria:

• 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 time of dosing).
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• Evidence of gout/hyperuricemia, measured sUA >8 mg/dL at screening.
• Experienced an episode of nephrolithiasis or ureterolithiasis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1-PF-06743649 or placebo; Subjects will be randomized to receive PF-06743649 or placebo as 2 single doses in periods 1 and 2 either in the fed or fasted state followed by once daily dosing for 14 days in period 3	Drug: PF-06743649; 40 mg tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet once daily dosing for 14 days; Drug: Placebo; Placebo tablet once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; Tablet, to be decided dose, once daily, 14 days; Drug: Placebo; Tablet, once daily, 14 days
Experimental: Cohort 2-PF-06743649 or placebo	Drug: PF-06743649; 40 mg tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet once daily dosing for 14 days; Drug: Placebo; Placebo tablet once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; Tablet, to be decided dose, once daily, 14 days; Drug: Placebo; Tablet, once daily, 14 days
Experimental: Cohort 3-PF-06743649 or placebo	Drug: PF-06743649; 40 mg tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet once daily dosing for 14 days; Drug: Placebo; Placebo tablet once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; Tablet, to be decided dose, once daily, 14 days; Drug: Placebo; Tablet, once daily, 14 days
Experimental: Cohort 4-PF-06743649 or placebo	Drug: PF-06743649; 40 mg tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet once daily dosing for 14 days; Drug: Placebo; Placebo tablet once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; Tablet, to be decided dose, once daily, 14 days; Drug: Placebo; Tablet, once daily, 14 days
Experimental: Cohort 5-PF-06743649 or placebo	Drug: PF-06743649; 40 mg tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet once daily dosing for 14 days; Drug: Placebo; Placebo tablet once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time once with a meal and once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; To be decided dose, tablet, one time without a meal, followed by once daily dosing for 14 days; Drug: Placebo; Placebo tablet one time once without a meal, followed by once daily dosing for 14 days; Drug: PF-06743649; Tablet, to be decided dose, once daily, 14 days; Drug: Placebo; Tablet, once daily, 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax)	up to 14 days
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)	up to 14 days
Time to Reach Maximum Observed Plasma Concentration (Tmax)	up to 14 days
Plasma Decay Half-Life (t1/2)	up to 14 days
Amount of drug recovered unchanged in urine during the dosing interval (Aetau)	up to 14 days
Percent of dose recovered unchanged in urine during the dosing interval(Aetau%)	up to 14 days
Renal clearance (CLr)	up to 14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in serum uric acid level	up to 14 days
Change from baseline in serum levels of xanthine and hypoxanthine	up to 14 days
Urinary uric acid levels	up to 14 days
Urinary xanthine levels	up to 14 days
Urinary hypoxanthine levels	up to 14 days

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 28, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Estimate): January 19, 2015
• Last Update Submitted That Met QC Criteria: January 16, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: tolerability; safety; PK; Multiple dose
• Other Study ID Numbers: B7911001