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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: October 30, 2008
• First Submitted That Met QC Criteria: October 30, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Estimate): June 2, 2009
• Last Update Submitted That Met QC Criteria: May 28, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: First in Human (FIH), PF-03716539, PK enhancer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Protease Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Midazolam; Maraviroc; Darunavir
• Other Study ID Numbers: B0831001