Single Dose Study Of The Effect Of Cyclosporine On The Pharmacokinetics Of PF-04991532 In Health Volunteers

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the pharmacokinetics, safety and tolerability of a single dose of PF-04991532 in healthy adult subjects with and without co-administration of cyclosporine.

Official Title
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A Phase 1, Single-Dose, Open-Label, Crossover Study To Assess The Effect Of Cyclosporine On The Pharmacokinetics Of PF-04991532 In Healthy Adult Subjects

Conditions
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Healthy, Drug Interaction

Intervention / Treatment
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* Drug: PF-04991532 alone
* Drug: PF-04991532 + cyclosporine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female (non-childbearing potential) subjects 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 pulse rate measurement, 12-lead ECG and clinical laboratory tests. Women must be of non childbearing potential as defined in Lifestyle Guidelines. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). An informed consent document signed and dated by the subject or a legally acceptable representative. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, sychiatric, neurologic, or allergic (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) disease or clinical findings at Screening. Subjects with clinically significant infections within the past 3 months (for example, those requiring hospitalization, or as judged by the Investigator), or evidence of any infection within the past 7 days. Screening supine blood pressure >=140 mm Hg (systolic) or >=90 mm Hg (diastolic), on a single measurement [confirmed by a single repeat, if necessary] following at least 5 minutes of rest.

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-04991532 alone<br> | Drug: PF-04991532 alone<br>* a single dose of 150 mg PF-04991532, fasted<br>|
| Experimental: PF-04991532 + cyclosporine<br> | Drug: PF-04991532 + cyclosporine<br>* a single dose of 150 mg PF-04991532 + a single dose of 600 mg cyclosporine, fasted<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time profile (AUC) |  | predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 36, 48, 72 hrs postdose | 
| Max observed plasma concentration (Cmax) |  | predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 36, 48, 72 hrs postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Cmax (Tmax) |  | predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 36, 48, 72 hrs postdose | 
| Terminal elimination half-life (t1/2) |  | predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 36, 48, 72 hrs postdose | 
| Total amount of unchanged drug excreted in the urine over 24 hours (Ae24) |  | 0-8, and 8-24hr postdose | 
| Renal clearance (CLR) |  | 0-24hr | 
| Total amount of unchanged drug excreted in the urine over 24 hours, expressed as percent of dose (Ae24(% excreted)) |  | 0-24hr |