A Study To Evaluate The Safety, Tolerability And Plasma Drug Levels Following A Single Dose Of PF-04995274 In Healthy Adult Volunteers

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-04995274 after administration of a single dose to healthy volunteers, and to evaluate the plasma drug concentrations after single dose in healthy volunteers.

Detailed Description
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The purpose is to evaluate the safety and pharmacokinetics of a single dose of PF-04995274 in healthy adult volunteers.

Official Title
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A Phase 1, First-Into-Human, Escalating Dose Trial To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of PF-04995274 After Administration Of Single Oral Doses To Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-04995274
* Drug: PF-04995274
* Drug: PF-04995274
* Drug: PF-04995274


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all cohorts, healthy male and/or female subjects of nonchildbearing potential between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and heart rate measurement, 12 lead ECG and clinical laboratory tests). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Pregnant or nursing women; women of childbearing potential. Female subjects must be of non childbearing potential defined by a history of surgical sterilization (eg, hysterectomy or bilateral oophorectomy) or post menopausal status (complete absence of menses for at least two consecutive years) and elevated FSH concentration in women between 45 and 55.

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Single dose 3 period interleaved cross-over with placebo substitution | Drug: PF-04995274<br>* Planned single PO 0.15mg, 1.5mg, 15mg doses of PF-04995274 interleaved with cohort 2 such that doses escalate from 0.15 mg to 50 mg.<br>|
| Experimental: Cohort 2<br>Single dose 4 period interleaved cross-over, placebo substitution, with food effect | Drug: PF-04995274<br>* Planned single PO 0.5mg, 5mg, 50mg doses of PF-04995274, interleaved with cohort 2 such that doses escalate from 0.15 mg to 50 mg interleaved with cohort 2 such that doses escalate from 0.15 mg to 50 mg.<br>|
| Experimental: Cohort 3<br>Single dose 4 period cross-over, placebo insertion, with food effect | Drug: PF-04995274<br>* Planned single PO 120mg and 210mg doses of PF-04995274<br>|
| Experimental: Optional Cohort 4<br>Single dose 3 period cross-over with placebo substitution | Drug: PF-04995274<br>* single PO dose of PF-04995274; dosage to be determined by safety and pharmacokinetic data<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoints (AE's, Vital signs (supine & standing BP, PR), Triplicate ECG, 8 hours of cardiac telemetry postdose, Clinical safety laboratory endpoints, Digit Symbol Substitution Test (DSST), Drug Effect Questionnaire (DEQ), Clinical |  | up to 21 days post dose | 
| examinations) |  | up to 21 days post dose | 
| Cmax, Tmax, AUClast, AUCinf, and t1/2 of PF 04995274, as the data permit. |  | up to 7 days post dose | 
| Cmax, Tmax, AUClast, AUCinf, and t1/2 of PF 05082547, as the data permit. |  | up to 7 days post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma aldosterone concentrations |  | through 1 day post dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteer, safety, pharmacokinetic