A Single Dose Escalation Study In Healthy Volunteers To Determine The Pharmacokinetics, Safety And Tolerability Of PF-05089771 In Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01259882
First received: November 30, 2010
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

This is a two part study. The purpose of the first part is primarily to determine the safety and toleration and pharmacokinetics of PF-05089771 following single escalating doses. Secondary objectives will be to investigate the PK of an alternative formulation of PF-05089771 and the effect of food on the PK of PF-05089771. The second part of the study will focus on investigation of the exploratory pharmacodynamics of PF-05089771 using novel biomarkers in healthy volunteers. The doses selected in Part B will have been administered previously in Part A of the study.


Condition Intervention Phase
Pain
Drug: PF-05089771
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double Blind (3rd Party Open) Randomized, Placebo Controlled, Crossover Dose Escalation Study To Investigate The Safety, Toleration, Pharmacokinetics And Exploratory Pharmacodynamics Of PF-05089771 In Healthy Volunteers

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of participants with adverse events as a measure of safety and tolerability of PF-05089771. [ Time Frame: Days 1-3 ] [ Designated as safety issue: Yes ]
  • Maximum concentration (Cmax) for PF-05089771 in plasma (measured in ng/mL) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Tmax = Time of maximum concentration of PF-05089771 in plasma (hr) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • AUClast = Area under the curve from the time of dosing to the last data point taken (ng.hr/mL) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • MRT = Mean residence time of PF-05089771 in the body (hr) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Heat Pain Perception Threshold (HPPT). Measured by applying a heat thermode to the thigh for 1 minute at 47oC. HPPT will be measured at 3 separate doses plus placebo in 12 healthy volunteers. [ Time Frame: Hours 1-6 post dose. ] [ Designated as safety issue: No ]
  • Long Thermal Stimulation (LTS). Measured by applying a heat thermode to the thigh at 48oC for 5 seconds. will be measured at 3 separate doses plus placebo in 12 healthy volunteers [ Time Frame: Hours 1-6 post dose. ] [ Designated as safety issue: No ]
  • Odor threshold (Sniffin' Sticks). Measured with Sniffin Sticks. Will be measured at 3 separate doses plus placebo in 12 healthy volunteers [ Time Frame: Hours 1-6 post dose. ] [ Designated as safety issue: No ]
  • Urine: Aet (amount excreted in urine), Aet% and CLr for selected doses dependent on the emerging pharmacokinetics of PF-05089771 where t = 24 hours. [ Time Frame: Up to 24 hours ] [ Designated as safety issue: No ]
  • AUCinf = Area under the curve from the time of dosing extrapolated to infinity (ng.hr/mL) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • AUC24 = Area under the curve from the time of dosing to 24 hours post dose (ng.hr/mL) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • CI/F = Clearance of PF-05089771 from plasma corrected for systemic compound availability (L/hr) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • t½ = Elimination half life of PF-05089771 (hr) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • C8 hour = concentration of PF-05089771 in the plasma 8 hours post dose (ng/mL) [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: December 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Experimental intervention: PF-05089771 or placebo
Cohort 1
Drug: PF-05089771
Subjects will receive single ascending doses of PF-05089771 or placebo to investigate the safety/tolerability and PK of PF-05089771. The PK of alternative formulations of PF-05089771 and the effect of food on PK may also be investigated.
Experimental: Cohort 2: Experimental intervention: PF-05089771 or placebo
Cohort 2
Drug: PF-05089771
Subjects will receive single ascending doses of PF-05089771 or placebo to investigate the safety/tolerability and PK of PF-05089771. The PK of alternative formulations of PF-05089771 and the effect of food on PK may also be investigated.
Experimental: Cohort 3: Experimental intervention: PF-05089771 or placebo
Cohort 3
Drug: PF-05089771
Subjects will receive single doses of PF-05089771 or placebo in a fully randomized crossover design. The investigation of the safety/tolerability and PK of PF-05089771 will occur. In addition the exploratory pharmacodynamics of PF-05089771 will be investigated using novel biomarkers.
Experimental: Cohort 4: Experimental intervention: PF-05089771 or placebo
Cohort 4
Drug: PF-05089771
Subjects will receive single doses of PF-05089771 or placebo in a fully randomized crossover design. The investigation of the safety/tolerability and PK of PF-05089771 will occur.
Experimental: Cohort 5: Experimental intervention: PF-05089771 or placebo
Cohort 5
Drug: PF-05089771
Subjects will receive single doses of PF-05089771 or placebo in a fully randomized crossover design. The investigation of the safety/tolerability and PK of PF-05089771 will occur.
Experimental: Cohort 6: Experimental intervention: PF-05089771 or placebo
Cohort 6
Drug: PF-05089771
Subjects will receive single doses of PF-05089771 or placebo in a fully randomized crossover design. The investigation of the safety/tolerability and PK of PF-05089771 will occur.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male subjects or female subjects of non-child bearing potential between the ages of 18 and 55 years, inclusive.
  • 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
  • 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, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
  • Any condition possibly affecting drug absorption (e.g., gastrectomy).
  • A positive urine drug screen.
  • History of regular alcohol consumption exceeding 21 drinks/week (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.
  • Treatment with an investigational drug within 60 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.
  • 12-lead ECG demonstrating QTc >450 msec at screening. If QTc exceeds 450 msec, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the subject's eligibility.
  • Females of child bearing potential.
  • Use of prescription or non-prescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal supplements must be discontinued 28 days prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of 1 g/day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.
  • Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing. History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Unwilling or unable to comply with the Lifestyle guidelines described in this protocol.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01259882

Locations
Belgium
Pfizer Investigational Site
Bruxelles, Belgium, B-1070
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01259882     History of Changes
Other Study ID Numbers: B3291001
Study First Received: November 30, 2010
Last Updated: January 31, 2012
Health Authority: Belgium: Ethics Committee

Keywords provided by Pfizer:
Pharmacokinetics Safety Tolerability Pharmacodynamics

ClinicalTrials.gov processed this record on August 18, 2014