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

Official Title: “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.

Intervention(s) in this Clinical Trial

• 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)
• 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
• 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)
• Drug: Maraviroc
  • Maraviroc 150 mg tablet once daily for 6 days (Days 1-6)
• Drug: Maraviroc +PF-03716539
  • Maraviroc 150 mg tablet, single dose plus PF-03716539 100 mg oral solution, single dose (Day 7)
• Drug: Maraviroc
  • Maraviroc 225 mg tablet once daily for 6 days (Days 1-6)
• Drug: Maraviroc +PF-03716539
  • Maraviroc 225 mg tablet, single dose plus PF-03716539 200 mg oral solution, single dose (Day 7)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Cohort 1
  • PF-03716539 crossover, single dose escalation (doses subject to change).
• Experimental: Cohort 2
  • PF-03716539 crossover, single dose escalation (doses subject to change).
• Experimental: Cohort 3
  • Midazolam-PF-03716539 drug-drug interaction (PF-03716539 doses subject to change).
• Experimental: Cohort 4
  • Darunavir-PF-03716539 drug-drug interaction (PF-03716539 doses subject to change).
• Experimental: Cohort 5
  • Maraviroc-PF-03716539 drug-drug interaction (PF-03716539 doses subject to change).
• Experimental: Cohort 6
  • Maraviroc-PF-03716539 drug-drug interaction (PF-03716539 200 mg).

Primary Measures

• 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.
  • Time Frame: 27 days
    Safety Issue?: Yes
• To explore the pharmacokinetics of escalating single oral doses of PF 03716539 in healthy adult subjects.
  • Time Frame: 6 days
    Safety Issue?: No

Secondary Measures

• To assess the potency of PF 03716539 for CYP3A4 inhibition utilizing single dose IV midazolam as a probe substrate for CYP3A4/5.
  • Time Frame: 6 days
    Safety Issue?: No
• To evaluate the potential of PF 03716539 to enhance or "boost" the pharmacokinetics of both darunavir and maraviroc.
  • Time Frame: 8 days
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Pfizer Industry

Overall Clinical Trial Officials and Contacts

Pfizer CT.gov Call Center Study Director Pfizer  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00783484

Study ID Number: B0831001

ClinicalTrials.gov Identifier: NCT00783484

Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

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