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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 September 16, 2014