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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (N=10)<br>Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active) | Drug: PF-04634817<br>* Oral solution of PF-04634817 at 3 mg will be given once daily for 14 days.<br>|
| Experimental: Cohort 2 (N=10)<br>Placebo-controlled, multiple doses of PF-04634817 at 3 mg per day for 14 days. (2 placebo: 8 active) | Drug: PF-04634817<br>* Oral solution of PF-04634817 at 3 mg will be given once daily for 14 days.<br>|
| Experimental: Cohort 3 (N=10)<br>Placebo-controlled, multiple doses of PF-04634817 at 30 mg per day for 14 days. (2 placebo: 8 active) | Drug: PF-04634817<br>* Oral solution of PF-04634817 at 30 mg will be given once daily for 14 days.<br>|
| Experimental: Cohort 4 (N=10)<br>Placebo-controlled, multiple doses of PF-04634817 at 100 mg per day for 14 days. (2 placebo: 8 active) | Drug: PF-04634817<br>* Oral solution of PF-04634817 at 100 mg will be given once daily for 14 days.<br>|
| Experimental: Cohort 5 (N=10)<br>Placebo-controlled, multiple doses of PF-04634817 at 300 mg per day for 14 days. (2 placebo: 8 active) | Drug: PF-04634817<br>* Oral solution of PF-04634817 at 300 mg will be given once daily for 14 days.<br>|
| Experimental: Cohort 6 (N=10) Optional cohort<br>Placebo-controlled, multiple doses of PF-04634817 up to 300 mg per day for 14 days. (2 placebo: 8 active) | Drug: PF-04634817<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers, pharmacokinetics, safety, tolerability, multiple dosing, Diabetic Nephropathies