Clinical trial NCT01529671: A Safety And Tolerability Study Of PF-05089771 In Healthy Subjects And In Subjects With Otseoarthritis Of The Knee
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pain
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-02-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events as a measure of safety and tolerability of PF-05089771
timeFrame: Days 1-16
measure: Maximum concentration (Cmax) for PF-05089771 in plasma (measured in ng/mL)
timeFrame: Days 1, 4 and 14
measure: Tmax = Time of maximum concentration of PF-05089771 in plasma (hr)
timeFrame: Days 1, 6 and 14
measure: AUCtau= Area under the curve from the time of dosing to the next dose (ng.hr/mL)
timeFrame: Days 1, 6 and 14
measure: Elimination half life (hr) = rate of elimination of PF-05089771 after the final dose
timeFrame: day 14 PK samples collected only for 48 hours
Secondary outcomes:
measure: AUCinf = Area under the curve from the time of dosing extrapolated to infinity (ng.hr/mL)
timeFrame: Days 14, over 48 hours of PK samples collection
measure: Daily pain score throughout the treatment period using an 11-point Numeric Rating Scale (NRS).
timeFrame: Days 14, every day over 24 hours
measure: Daily time to ascend and descend stairs.
timeFrame: Days 14, every day over 24 hours
measure: Daily pain following stair climbing and descending
timeFrame: Days 14, every day over 24 hours
measure: Daily time for self paced walk
timeFrame: Days 14, every day over 24 hours
measure: Daily pain following self paced walk.
timeFrame: Days 14, every day over 24 hours
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: