A Safety And Tolerability Study Of PF-05089771 In Healthy Subjects And In Subjects With Otseoarthritis Of The Knee

An Investigator And Subject Blinded, Sponsor Open, Randomized, Placebo Controlled, Multiple Dose Study To Investigate The Safety, Toleration And Pharmacokinetics Of Multiple Oral Doses Of Pf-05089771 In Healthy Subjects And In Subjects With Osteoarthritis Of The Knee

The purpose of the study is primarily to determine the safety and toleration and pharmacokinetics of PF-05089771 following escalating multiple doses lasting for 14 days.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: PF-05089771; Drug: PF-05089771

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male subjects or female subjects of non-child bearing potential between the ages of 18 and 55 years, inclusive.
• elderly cohort : healthy male and/or female subjects of 65 and 74 years,
• cohort 3: subjects with osteoarthritis of the knee: Male or female subjects not of child bearing potential between the ages of 18 and 75 years inclusive at the time of entering the study.

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 (eg, gastrectomy).
• A positive urine drug screen.
• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (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 or a QRS interval >120 msec at Screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.
• 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.
• 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) or more 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.

for cohort 3: Evidence of relapse or recurrence of clinically significant endocrine, metabolic, pulmonary, hepatic, osteo-mio-artricular, gastrointestinal, cardiovascular, renal, , psychiatric or neurological disease, or neurological disease less than 28 days prior to screening.

Symptomatic OA of the hip ipsilateral to index knee which the patient considers more painful than the knee. History of diseases other than OA that may involve the index knee in the last 12 months prior to screening, including but not limited to: inflammatory joint diseases (i.e rehumatoid arthritis and gout), calcium crystal diseases, bursitis, tendinitis, tumors and cysts, ligament injuries, bone fractures, post-infective pathologies; widespread chronic pain conditions (ie, fibromyalgia) and neuropathic disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Experimental intervention: PF-05089771 or placebo; Subjects will receive multiple doses of PF-05089771 or placebo twice daily to investigate the safety/tolerability and Pharmacokinetics (PK) of PF-05089771.	Drug: PF-05089771; PF-05089771 will be dosed as a suspension twice daily (BID); Drug: PF-05089771; PF-05089771 will be dosed as a suspension BID
Experimental: Cohort 2: Experimental intervention: PF-05089771 or placebo; Subjects will receive multiple doses of PF-05089771 or placebo twice daily to investigate the safety/tolerability and PK of PF-05089771.	Drug: PF-05089771; PF-05089771 will be dosed as a suspension twice daily (BID); Drug: PF-05089771; PF-05089771 will be dosed as a suspension BID
Experimental: Cohort 3: Experimental intervention: PF-05089771 or placebo; Subjects with osteoarthritis of the knee will receive multiple doses of PF-05089771 or placebo twice daily to investigate the safety/tolerability and Pharmacokinetic (PK) of PF-05089771.	Drug: PF-05089771; PF-05089771 will be dosed as a suspension twice daily (BID); Drug: PF-05089771; PF-05089771 will be dosed as a suspension BID
Experimental: Cohort 4: Experimental intervention: PF-05089771 or placebo; Elderly Subjects will receive multiple doses of PF-05089771 or placebo twice daily to investigate the safety/tolerability and Pharmacokinetic (PK) of PF-05089771.	Drug: PF-05089771; PF-05089771 will be dosed as a suspension twice daily (BID); Drug: PF-05089771; PF-05089771 will be dosed as a suspension BID
Experimental: Cohort 5: Experimental intervention: PF-05089771 or placebo; Subjects will receive multiple doses of PF-05089771 or placebo twice daily to investigate the safety/tolerability and PK of PF-05089771.	Drug: PF-05089771; PF-05089771 will be dosed as a suspension twice daily (BID); Drug: PF-05089771; PF-05089771 will be dosed as a suspension BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability of PF-05089771	Days 1-16
Maximum concentration (Cmax) for PF-05089771 in plasma (measured in ng/mL)	Days 1, 4 and 14
Tmax = Time of maximum concentration of PF-05089771 in plasma (hr)	Days 1, 6 and 14
AUCtau= Area under the curve from the time of dosing to the next dose (ng.hr/mL)	Days 1, 6 and 14
Elimination half life (hr) = rate of elimination of PF-05089771 after the final dose	day 14 PK samples collected only for 48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
AUCinf = Area under the curve from the time of dosing extrapolated to infinity (ng.hr/mL)	Days 14, over 48 hours of PK samples collection
Daily pain score throughout the treatment period using an 11-point Numeric Rating Scale (NRS).	Days 14, every day over 24 hours
Daily time to ascend and descend stairs.	Days 14, every day over 24 hours
Daily pain following stair climbing and descending	Days 14, every day over 24 hours
Daily time for self paced walk	Days 14, every day over 24 hours
Daily pain following self paced walk.	Days 14, every day over 24 hours

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: February 6, 2012
• First Submitted That Met QC Criteria: February 6, 2012
• First Posted (Estimate): February 9, 2012

Study Record Updates

• Last Update Posted (Estimate): December 12, 2012
• Last Update Submitted That Met QC Criteria: December 10, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Other Study ID Numbers: B3291011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No