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Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen

Sponsor: Pfizer
Study Drug: Celebrex 100 mgm-200mgm BID vs. Motrin 600-800 TID or Naprosyn 375-500 BID
Protocol: A3191172
Phase 4
CRO: Quintiles
Site #:
Central Lab: MDS
IRB: Schulman IRB
Subjects 20,000 / 800 Sites -> 25 Subjects per Site

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more or equals 18
OA or RA x at least 6 months requiring treatment
Requires chronic daily NSAID’s to control arthritis
Carotid Sono more or equals 50 %
Symptomatic PVD
High Risk for ASVD with at least 3 of the following:
1. Age > 55
2. HTN
3. Hyperlipidemia
4. FH CVD or Stroke
5. Current Smoking > 15 per day
6. Microalbuminuria (Urine Protein/Creatinine Ratio > 2)
7. LVH
8. ABI < 0.9

Prednisone > 20 mgm and/or not stable dose
Cardiac event within 3 months
CHF Class III or IV
LFT’s > 2x
ASA > 325 mgm daily
Creatinine Men: > 1.7 Women: > 1.5

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V1 D -14 Lab, Begin single-blind Placebo, ICF, EKG, +/- 3 Days

V2 D 1 Lab, Baseline, Randomize double-blind study drug

V3 D 7 Continue Double-Blind Treatment Period

V4 D 14 Lab for PK

V5 D 28 Lab for PK, Early Termination

V6 D 42 Lab, Follow-up/End of Study

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Study to test safety of painkillers on heart patients
By Steve Sternberg, USA TODAY
A major global study involving thousands of heart patients with arthritis will test the relative safety of three popular painkillers in people with heart disease, doctors said Tuesday.
The study will pit Celebrex, Naproxen and Ibuprofen against one another in 20,000 patients in the USA, Canada, Latin America, Europe and Australia. The study will be the first head-to-head trial of the painkillers' safety and the first such test done in such high-risk patients, says lead investigator Steven Nissen of the Cleveland Clinic.
"Patients come into my office all the time and ask me what drug is safe for them to take," Nissen says. "This will be the definitive test to answer that question."
Nissen says the research also aims to restore the public confidence in painkillers that was shaken in 2001 when he and Cleveland Clinic colleague Eric Topol reported that the blockbuster Vioxx increased patients' heart attack and stroke risk.
After that study, Vioxx and its chemical cousin Bextra were taken off the market, leaving Pfizer's Celebrex as the only Cox-2 inhibitor drug still being sold, but with a strong warning on its label.
Cox-2 inhibitors are members of a class of non-steroidal anti-inflammatory drugs, or NSAIDs. The selling point for Cox-2 inhibitors was that they eased pain with less stomach discomfort than older pain relievers. As a result of the Vioxx controversy, many people who need pain relief switched to over-the-counter NSAIDS. Earlier this year, the Food and Drug Administration warned that these drugs too may pose risks to the heart.
The new study will test Celebrex and two well-known types of NSAIDs: ibuprofen, sold under such brand names as Motrin and Advil, and naproxen, sold as Naprosyn and Alleve.
Pfizer is funding the study, which will cost an estimated $100 million, Nissen says. But the company will play no role in analyzing the data, which will be made publicly available through the National Heart, Lung, and Blood Institute to eliminate the possibility that an investigator could tip the balance toward one drug or another by selectively reporting results, Nissen says.
Thomas Fleming, chairman of the Department of Biostatistics at the University of Washington, Seattle, will head a committee that will independently monitor the trial and have the authority to stop it if safety questions emerge.
"This is an extremely important issue," Fleming says. "This is ... needed to provide insights into the safety and role of Cox-2 inhibitors, in this case Celebrex, vs. naproxen and ibuprofen."
Last week, The New England Journal of Medicine stated that Merck did not include data on three patients suffering heart attacks in a previous study of its drug Vioxx.
Merck responded that the heart attacks were reported to the FDA and to the public.