A Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Single Oral Doses Of PF-03716539 In Healthy Adult Subjects

Study Overview
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Brief Summary
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First in human study to evaluate the safety, tolerability, and pharmacokinetics of PF-03716539. The potential of PF-03716539 to increase the concentrations of midazolam, darunavir and maraviroc will also be evaluated.

Official Title
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A Double-Blind (3rd Party Open), Placebo-Controlled, Crossover, Dose Escalating Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Single Oral Doses Of PF-03716539, To Assess The Potential Of PF-03716539 To Inhibit CYP3A4 (In Vivo) And To Evaluate The Drug Interaction Potential Between PF-03716539 And Darunavir Or Maraviroc In Healthy Adult Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: PF-03716539
* Drug: PF-03716539
* Drug: PF-03716539
* Other: Placebo
* Drug: PF-03716539
* Drug: PF-03716539
* Drug: PF-03716539
* Other: Placebo
* Drug: Midazolam
* Drug: Midazolam + PF-03716539 (100 mg)
* Drug: Midazolam + PF-03716539 (50 mg)
* Drug: Darunavir
* Drug: Darunavir + PF-03716539
* Drug: Maraviroc
* Drug: Maraviroc +PF-03716539
* Drug: Maraviroc
* Drug: Maraviroc +PF-03716539


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. Body Mass Index (BMI) of approximately 18 to 30 kg/m2. Total body weight >50 kg (110 lbs). Exclusion Criteria: Pregnant or nursing females. females of childbearing potential. Evidence or history of clinically significant hematological, renal (including kidney stones), endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or clinical findings at screening. Treatment with an investigational drug within 30 days (or determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>PF-03716539 crossover, single dose escalation (doses subject to change). | Drug: PF-03716539<br>* PF-03716539 10 mg oral solution, single dose<br>Drug: PF-03716539<br>* PF-03716539 25 mg oral solution, single dose<br>Drug: PF-03716539<br>* PF-03716539 3 mg oral solution, single dose<br>Other: Placebo<br>* Placebo for 3 mg, 10 mg and 25 mg of PF-03716539 (single dose)<br>|
| Experimental: Cohort 2<br>PF-03716539 crossover, single dose escalation (doses subject to change). | Drug: PF-03716539<br>* PF-03716539 100 mg oral solution, single dose<br>Drug: PF-03716539<br>* PF-03716539 200 mg oral solution, single dose<br>Drug: PF-03716539<br>* PF-03716539 50 mg oral solution, single dose<br>Other: Placebo<br>* Placebo for 50 mg, 100 mg and 200 mg of PF-03716539 (single dose)<br>|
| Experimental: Cohort 3<br>Midazolam-PF-03716539 drug-drug interaction (PF-03716539 doses subject to change). | Drug: Midazolam<br>* Midazolam 1 mg IV, single dose<br>Drug: Midazolam + PF-03716539 (100 mg)<br>* Midazolam 1 mg IV, single dose plus PF-03716539 100 mg oral solution, single dose<br>Drug: Midazolam + PF-03716539 (50 mg)<br>* Midazolam 1 mg IV, single dose plus PF-03716539 50 mg oral solution, single dose<br>|
| Experimental: Cohort 4<br>Darunavir-PF-03716539 drug-drug interaction (PF-03716539 doses subject to change). | Drug: Darunavir<br>* Darunavir 600 mg tablet twice daily for 9 days (Days 1-9)<br>Drug: Darunavir + PF-03716539<br>* Darunavir 600 mg tablet, single dose plus PF-03716539 50 mg oral solution, single dose (Day 10)<br>|
| Experimental: Cohort 5<br>Maraviroc-PF-03716539 drug-drug interaction (PF-03716539 doses subject to change). | Drug: Maraviroc<br>* Maraviroc 150 mg tablet once daily for 6 days (Days 1-6)<br>* Other names: Selzentry;Drug: Maraviroc +PF-03716539<br>* Maraviroc 150 mg tablet, single dose plus PF-03716539 100 mg oral solution, single dose (Day 7)<br>* Other names: Selzentry;|
| Experimental: Cohort 6<br>Maraviroc-PF-03716539 drug-drug interaction (PF-03716539 200 mg). | Drug: Maraviroc<br>* Maraviroc 225 mg tablet once daily for 6 days (Days 1-6)<br>* Other names: Selzentry;Drug: Maraviroc +PF-03716539<br>* Maraviroc 225 mg tablet, single dose plus PF-03716539 200 mg oral solution, single dose (Day 7)<br>* Other names: Selzentry;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of escalating single oral doses of PF 03716539 administered as Extemporaneous Powder for Solution (EPS) in healthy adult subjects. |  | 27 days | 
| To explore the pharmacokinetics of escalating single oral doses of PF 03716539 in healthy adult subjects. |  | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the potency of PF 03716539 for CYP3A4 inhibition utilizing single dose IV midazolam as a probe substrate for CYP3A4/5. |  | 6 days | 
| To evaluate the potential of PF 03716539 to enhance or boost the pharmacokinetics of both darunavir and maraviroc. |  | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First in Human (FIH), PF-03716539, PK enhancer