Clinical trial NCT01140672: A Multiple Dose Study To Determine Safety, Tolerability, and Pharmacokinetics Of PF-04634817 In Healthy Adult Subjects
Official title: A Double Blind, 3rd Party Open, Placebo Controlled, Dose Escalating, Parallel Study To Investigate The Safety, Toleration And Pharmacokinetics Of Multiple Oral Doses Of PF-04634817 In Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Healthy volunteers
pharmacokinetics
safety
tolerability
multiple dosing
Diabetic Nephropathies
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-06-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events, supine and standing vital sign measurements, 12-lead ECGs, blood and urine safety tests.
timeFrame: 14 days
measure: 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.
timeFrame: 14 days
measure: 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).
timeFrame: 14 days
measure: 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.
timeFrame: 14 days
measure: Pharmacodynamic: MCP-1 change from baseline.
timeFrame: 14 days
Secondary outcomes:
measure: Pharmacodynamic: p-ERK Inhibition in human monocytes: percent inhibition of monocyte p-ERK activity relative to the pre-dose baseline value
timeFrame: 14 days
measure: MIP-1β stimulated CCR5 receptor internalization: percent inhibition of internalization relative to the pre-dose baseline value
timeFrame: 14 days
measure: Absolute and percent change in circulating monocytes; Absolute and percent change in CD14+CD16+ monocytes.
timeFrame: 14 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer Investigational Site
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: