A Multiple Dose Study To Determine Safety, Tolerability, and Pharmacokinetics Of PF-04634817 In Healthy Adult Subjects

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT01140672
First received: June 8, 2010
Last updated: June 7, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: PF-04634817
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
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

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Adverse events, supine and standing vital sign measurements, 12-lead ECGs, blood and urine safety tests. [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Pharmacodynamic: MCP-1 change from baseline. [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacodynamic: p-ERK Inhibition in human monocytes: percent inhibition of monocyte p-ERK activity relative to the pre-dose baseline value [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • MIP-1β stimulated CCR5 receptor internalization: percent inhibition of internalization relative to the pre-dose baseline value [ Time Frame: 14 days ] [ Designated as safety issue: No ]
  • Absolute and percent change in circulating monocytes; Absolute and percent change in CD14+CD16+ monocytes. [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: June 2010
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active)
Drug: PF-04634817
Oral solution of PF-04634817 at 3 mg will be given once daily for 14 days.
Experimental: Cohort 2 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active)
Drug: PF-04634817
Oral solution of PF-04634817 at 3 mg will be given once daily for 14 days.
Experimental: Cohort 3 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 30 mg per day for 14 days. (2 placebo: 8 active)
Drug: PF-04634817
Oral solution of PF-04634817 at 30 mg will be given once daily for 14 days.
Experimental: Cohort 4 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 100 mg per day for 14 days. (2 placebo: 8 active)
Drug: PF-04634817
Oral solution of PF-04634817 at 100 mg will be given once daily for 14 days.
Experimental: Cohort 5 (N=10)
Placebo-controlled, multiple doses of PF-04634817 at 300 mg per day for 14 days. (2 placebo: 8 active)
Drug: PF-04634817
Oral solution of PF-04634817 at 300 mg will be given once daily for 14 days.
Experimental: Cohort 6 (N=10) Optional cohort
Placebo-controlled, multiple doses of PF-04634817 up to 300 mg per day for 14 days. (2 placebo: 8 active)
Drug: PF-04634817
Cohort will only be dosed if necessary. Dose selected for this cohort may be a repeat of a previous cohort or intermediate dose not to exceed 300 mg.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01140672

Locations
United States, Connecticut
Pfizer Investigational Site
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT01140672     History of Changes
Other Study ID Numbers: B1261003
Study First Received: June 8, 2010
Last Updated: June 7, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Healthy volunteers
pharmacokinetics
safety
tolerability
multiple dosing
Diabetic Nephropathies

ClinicalTrials.gov processed this record on April 16, 2014