A Study Of PF-05190457 In Healthy Volunteers And Type-2 Diabetic Patients

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and tolerability of PF-05190457 after administration of multiple doses to healthy volunteers and Type 2 diabetic patients and to evaluate the plasma drug concentrations after multiple doses.

Official Title
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A Phase 1 Placebo-Controlled Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Ascending Doses Of PF-05190457 In Healthy And Type 2 Diabetic Adults

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: PF-05190457 or Placebo
* Drug: PF-05190457 or Placebo
* Drug: PF-05190457 or Placebo
* Drug: PF-05190457 or Placebo
* Drug: PF-05190457 or Placebo
* Drug: PF-05190457 or Placebo
* Drug: PF-05190457 or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females of non-childbearing potential between ages of 18 and 55 years, BMI of 18.5 to 30.5 kg/m^2, and weight between 50 and 100 kg, inclusive. Type 2 diabetic males and females of non-childbearing potential between ages of 18 and 55 years, BMI of 18.5 to 40.0 kg/m^2, weight between 50 and 150 kg, and HbA1c of 7.0-10.0%, inclusive. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease. Additionally, type 2 diabetic patients who have history of diabetic complications with significant end-organ damage or pharmacologic treatment for diabetes in addition to metformin.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 mg PF-05190457 or Placebo BID<br> | Drug: PF-05190457 or Placebo<br>* Twice daily oral doses of PF-05190457 or placebo is administered as a suspension for 14 days immediately before breakfast and dinner in healthy volunteers.<br>|
| Experimental: 10 mg PF-05190457 or Placebo BID<br> | Drug: PF-05190457 or Placebo<br>* Twice daily oral doses of PF-05190457 or placebo is administered as a suspension for 14 days immediately before breakfast and dinner in healthy volunteers.<br>|
| Experimental: 40 mg PF-05190457 or Placebo BID<br>Dose and dose frequency may be adjusted based on emerging safety and PK data. | Drug: PF-05190457 or Placebo<br>* Twice daily oral doses of PF-05190457 or placebo is administered as a suspension for 14 days immediately before breakfast and dinner in healthy volunteers.<br>|
| Experimental: 150 mg PF-05190457 or Placebo BID<br>Dose and dose frequency may be adjusted based on emerging safety and PK data. | Drug: PF-05190457 or Placebo<br>* Twice daily oral doses of PF-05190457 or placebo is administered as a suspension for 14 days immediately before breakfast and dinner in healthy volunteers.<br>|
| Experimental: 5 mg PF-05190457 or Placebo QD<br>Dose and dose frequency may be adjusted based on emerging safety and PK data. | Drug: PF-05190457 or Placebo<br>* Once daily oral doses of PF-05190457 or placebo is administered as a suspension for 14 days immediately before breakfast in healthy volunteers.<br>|
| Experimental: 50 mg PF-05190457 or Placebo QD<br>Dose and dose frequency may be adjusted based on emerging safety and PK data. | Drug: PF-05190457 or Placebo<br>* Once daily oral doses of PF-05190457 or placebo is administered as a suspension for 14 days immediately before breakfast in healthy volunteers.<br>|
| Experimental: xxx mg PF-05190457 or Placebo<br>Dose and dose frequency to be determined based on emerging safety and PK data. | Drug: PF-05190457 or Placebo<br>* Once (or twice) daily oral doses of PF-05190457 or placebo is administered as a suspension for 14 days immediately before breakfast (and dinner if twice) in Type 2 Diabetic patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events as a measure of safety and tolerability. |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The single and multiple dose pharmacokinetics of PF-05190457 will be described by estimating parameters of Area Under the Curve (AUC) and its accumulation ratio on days 1, 13, and 14, as appropriate and the data permit. |  | 2 weeks | 
| The single and multiple dose pharmacokinetics of PF-05190457 will be described by estimating parameters of Maximum Concentration (Cmax) on days 1, 13, and 14, as appropriate and the data permit. |  | 2 weeks | 
| The single and multiple dose pharmacokinetics of PF-05190457 will be described by estimating parameters of Time of Maximum concentration (Tmax) on days 1, 13, and 14, as appropriate and the data permit. |  | 2 weeks | 
| The single and multiple dose pharmacokinetics of PF-05190457 will be described by estimating parameters of the Minimum Amount of concentration (Cmin) on days 13 and 14, as appropriate and the data permit. |  | 2 weeks | 
| The single and multiple dose pharmacokinetics of PF-05190457 will be described by estimating parameters of Elimination of half-life (t ½ ) on day 14, as the data permit. |  | 2 weeks | 
| The single and multiple dose pharmacokinetics of PF-05190457 will be described by estimating parameters of apparent total clearance of the drug from plasma after oral administration (CL/F) on days 13 and 14, as the data permit. |  | 2 weeks | 
| The single and multiple dose pharmacokinetics of PF-05190457 will be described by estimating parameters of apparent volume of distribution during terminal phase after non-intravenous administration (Vz/F) on days 13 and 14, as the data permit. |  | 2 weeks | 
| Urinary recovery and renal clearance of PF-05190457 will be estimated via comparison of the plasma AUC and urinary excretion to provide AE0-τ, AE0-τ%, and CLR as the data permit. |  | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Multiple Ascending Doses, Safety, Pharmacokinetics, Healthy Volunteers, Type 2 Diabetic Patients