Effects of Dual Cyclooxygenase-2 and Carbonic Anhydrase Inhibition
Summary
Cyclooxygenase-2 (COX-2) inhibitors have become a common analgesic treatment option for patients with arthritis. However, long-term treatment has been associated with increased cardiovascular risk. With the past withdrawals and rejections of approval for COX-2 inhibitors the treatment options are now very limited.
This translates for example to about 10 million osteoarthritis patients in the US who cannot receive COX-2 inhibitors because of concomitant hypertension. And this exemplifies the unmet medical need to develop and offer safe treatment options for this particular patient population.
This trial investigates pharmacodynamic aspects of CG100649 which is being developed as a novel COX-2 inhibitor. Preclinical data show a dual mechanism of action, which consists of the inhibition of the two enzymes COX-2 and carbonic anhydrase-I/-II (CA-I/II) and through which the cardiovascular risk of COX-2 inhibition might be attenuated.
Description
Part 1 and 2 (staged analysis): Single dose of study drugs [celecoxib, placebo] followed by 3 days of blood draws as Period I; then after a wash-out phase, single dose of study drugs [CG100649 2mg and 8mg, celecoxib 200mg, placebo], followed by blood draws on 6 days and bi-weekly urine collections for 8 weeks.
Part 3: Five-way cross-over of single doses of study drugs with a CG100649 single dose level as determined by part 1 and 2, celecoxib 200mg, naproxen 500mg, acetazolamide 250mg and placebo.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Conditions
Healthy Volunteers
Intervention
CG100649 (2 mg), Celecoxib, Placebo capsules, Naproxen, Acetazolamide, CG100649 (8 mg)
Location
Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine
Philadelphia
Pennsylvania
United States
19104
Status
Active, not recruiting
Source
University of Pennsylvania
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00780325
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Bacterial Capsules
An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides.
Therapeutic Misconception
Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.
Naproxen
An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout.
Placebo Effect
An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.
Capsules
Hard or soft soluble containers used for the oral administration of medicine.
Clinical Trials
Trial for Studying Pharmacokinetic Effects of Ketoconazole on CG100649
This is a Phase I, open-labeled, randomization and 2x2 Cross trial to compare the pharmacokinetic effects between ketoconazole and CG100649 for healthy male volunteers.
Phase II Study of CG100649 for Primary Osteoarthritis in Male Subjects
The primary objective of this study is to evaluate the safety and efficacy of 3 loading and maintenance dose levels of CG100649 administered for 21 days in the treatment of osteoarthritis...
To study Celebrex versus naproxen to see if it decreases symptoms of juvenile arthritis such as pain and swelling.
Celecoxib Versus Naproxen for Prevention of Recurrent Ulcer Bleeding in Arthritis Patients
The aim of this study is to compare a PPI (esomeprazole) plus a COX-2 inhibitor (celecoxib) with a PPI plus a nonselective NSAID (naproxen) in preventing recurrent ulcer bleeding in arthri...
To compare the efficacy and safety of celecoxib versus placebo for the treatment of knee osteoarthritis (OA) in patients who were unresponsive to prescription strength naproxen and ibuprof...
PubMed Articles
Abstract Objective: To demonstrate that a fixed-dose combination of enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg has comparable efficacy to celecoxib for knee...
OBJECTIVES:: To test the superiority of naproxcinod over placebo in relieving hip osteoarthritis signs and symptoms, and assess its safety and effects on blood pressure (BP). METHODS:: A 13-week rando...
Objective: Further understand the safety profile of celecoxib and provide safety information for important adverse events (AEs). Methods: Analysis of randomized controlled trials from the Pfizer clini...
Abstract Background: Gastrointestinal (GI) tolerability is an important treatment consideration for physicians when choosing a nonselective nonsteroidal anti-inflammatory drug (NSAID) for their elderl...
OBJECTIVE: We explored effects of nonselective cyclooxygenase and selective cyclooxygenase 2 inhibition on collateral development in a model of chronic myocardial ischemia. We hypothesized that cycloo...
