A Multiple Dose Study To Determine Safety, Tolerability, and Pharmacokinetics Of PF-04634817 In Healthy Adult Subjects
- Registration Number
- NCT01140672
- Lead Sponsor
- Pfizer
- Brief Summary
The goals of this study are to evaluate the safety and tolerability of multiple ascending doses of PF-04634817 administered orally to healthy adult subjects. In additional, the plasma and urinary pharmacokinetics of multiple ascending doses of PF-04634817 administered orally to healthy adult subjects will be evaluated. Finally, the effect of multiple doses of PF-04634817 on circulating monocytes will be explored.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
Inclusion Criteria
- Healthy male and female (of non-childbearing potential) subjects 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
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease;
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication;
- Use of tobacco- or nicotine-containing products in excess of the equivalent of 5 cigarettes per day;
- Nursing females;
- Females of childbearing potential.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 (N=10) PF-04634817 Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active) Cohort 1 (N=10) PF-04634817 Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active) Cohort 3 (N=10) PF-04634817 Placebo-controlled, multiple doses of PF-04634817 at 30 mg per day for 14 days. (2 placebo: 8 active) Cohort 4 (N=10) PF-04634817 Placebo-controlled, multiple doses of PF-04634817 at 100 mg per day for 14 days. (2 placebo: 8 active) Cohort 5 (N=10) PF-04634817 Placebo-controlled, multiple doses of PF-04634817 at 300 mg per day for 14 days. (2 placebo: 8 active) Cohort 6 (N=10) Optional cohort PF-04634817 Placebo-controlled, multiple doses of PF-04634817 up to 300 mg per day for 14 days. (2 placebo: 8 active)
- Primary Outcome Measures
Name Time Method Adverse events, supine and standing vital sign measurements, 12-lead ECGs, blood and urine safety tests. 14 days Plasma PK Day 1: Cmax, Tmax, AUClast, AUCtau at all dose levels. Plasma PK Day 14: Cmax, Tmax, AUClast, AUCtau, AUCinf, t½, CL/F and Vss/F at all dose levels. 14 days AUCtau (Day 14) vs. AUCtau (Day 1) - estimate of accumulation ratio; Cmax (Day 14) vs. Cmax (Day 1); Tmax (Day 14) vs. Tmax (Day 1). 14 days Urinary PK: Aet (amount excreted in urine); Aet% at all doses of PF-04634817 where t = 24 hours on Day 1 and 14; CLr at all doses on Day 14. 14 days Pharmacodynamic: MCP-1 change from baseline. 14 days
- Secondary Outcome Measures
Name Time Method Pharmacodynamic: p-ERK Inhibition in human monocytes: percent inhibition of monocyte p-ERK activity relative to the pre-dose baseline value 14 days MIP-1β stimulated CCR5 receptor internalization: percent inhibition of internalization relative to the pre-dose baseline value 14 days Absolute and percent change in circulating monocytes; Absolute and percent change in CD14+CD16+ monocytes. 14 days
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇺🇸New Haven, Connecticut, United States