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 In Healthy Elderly Subjects
Overview
- Phase
- Phase 1
- Intervention
- PF-06743649
- Conditions
- Healthy Elderly
- Sponsor
- Pfizer
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Renal clearance (CLr)
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this study in healthy elderly 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male and/or female subjects between the ages of 65 and 85 years, inclusive. Ideally at least 25% of the subjects enrolled in each cohort will be 75 years of age and above at Screening. Subjects must be healthy as determined by the investigator based on a detailed medical history, full physical examination (including blood pressure and pulse rate measurement), 12-lead ECG and clinical laboratory test results. Subjects with mild, chronic, stable disease and on stable medication may be enrolled if deemed medically prudent by the investigator.
- •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.
Arms & Interventions
Cohort 1-PF-06743649 or placebo
Intervention: PF-06743649
Cohort 1-PF-06743649 or placebo
Intervention: Placebo
Cohort 2-PF-06743649 or placebo
Intervention: PF-06743649
Cohort 2-PF-06743649 or placebo
Intervention: Placebo
Cohort 3-PF-06743649 or placebo
Intervention: PF-06743649
Cohort 3-PF-06743649 or placebo
Intervention: Placebo
Cohort 4-PF-06743649 or placebo
Intervention: PF-06743649
Cohort 4-PF-06743649 or placebo
Intervention: Placebo
Cohort 5-PF-06743649 or placebo
Intervention: PF-06743649
Cohort 5-PF-06743649 or placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Renal clearance (CLr)
Time Frame: up to 14 days
Maximum Observed Plasma Concentration (Cmax)
Time Frame: up to 14 days
Percent of dose recovered unchanged in urine during the dosing interval(Aetau%)
Time Frame: up to 14 days
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: up to 14 days
Plasma Decay Half-Life (t1/2)
Time Frame: up to 14 days
Area Under the Curve from Time Zero to end of dosing interval (AUCtau)
Time Frame: up to 14 days
Amount of drug recovered unchanged in urine during the dosing interval (Aetau)
Time Frame: up to 14 days
Secondary Outcomes
- Urinary uric acid levels(up to 14 days)
- 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 xanthine levels(up to 14 days)
- Urinary hypoxanthine levels(up to 14 days)