Status:
TERMINATED
Effects of Dual Cyclooxygenase-2 and Carbonic Anhydrase Inhibition
Lead Sponsor:
University of Pennsylvania
Collaborating Sponsors:
CrystalGenomics, Inc.
Conditions:
Healthy Volunteers
Eligibility:
All Genders
18-60 years
Phase:
PHASE1
Brief 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. Wi...
Detailed 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 ...
Eligibility Criteria
Inclusion
- Age 18-60 years old, able and willing to provide written informed consent to participate in the study;
- Subjects must be in generally good health as determined by pre-study medical history, physical examination, clinical laboratory tests and 12-lead electrocardiogram (ECG);
- Body mass index (BMI) 19-32 kg/m2;
- Normal blood pressure (BP) \[systolic BP 90-140 mmHg, diastolic BP 50-90 mmHg\] and heart rate (HR) \[resting HR 45-90 bpm\] without medication;
- Clinical chemistry profile including electrolytes, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), creatinine, and urea must be within the normal range without medication; screening liver enzymes may be up to 1.5x normal range; screening CPK must be within 2x normal range without medication;
- Urinalysis including urinary creatinine must be within normal limits (trace findings and minor deviations are acceptable per the clinical decision of the Principal Investigator);
- Subjects must be non-smokers and non-drinkers or willing to abstain from smoking, alcohol, caffeine and high-fat foods for the duration of study;
- Subjects must be able to read, understand and follow the study instructions;
- Subjects and their sexual partners must agree to use double barrier contraception during the study period and for 2 months afterward or provide proof of surgical sterility. Double barrier contraception may include, but is not limited to, using a male condom with spermicide; having a female sexual partner who agrees to use an IUD with spermicide, a female condom with spermicide, a diaphragm with spermicide, a cervical cap with spermicide; or having a sterile sexual partner. Female subjects must be non-pregnant, non-lactating, and either postmenopausal for at least 1 year, surgically sterile for at least 3 months, or willing to use double barrier contraception from 28 days prior to study enrollment and/or their last confirmed menstrual period (whichever is longer) until 2 months after final clinic visit. For all females, the pregnancy test result must be negative at Screening;
- Subjects must tolerate the insertion of an intravenous line of the size ≥ 20 gauge for the drug administration study days.
Exclusion
- Use of any non-study medication(s) including low dose aspirin for cardiovascular prophylaxis within 2 weeks prior and 2 weeks after receipt of each dose of study drug;
- Use of chemotherapy agents or history of cancer, other than non-metastatic skin cancer that has been completely excised, within five (5) years prior to the screening visit;
- History of bacterial or viral infection requiring treatment with antibiotics or antivirals within 3 months of study;
- Presence or history of peripheral edema within the past 5 years;
- History of congestive heart failure;
- Use of drugs which are P450 3A4 inducers or inhibitors within the past 30 days (e.g. alprazolam, chlorpheniramine, cimetidine, fluoxetine, haloperidol, ketoconazole, itraconazole, erythromycin, clarithromycin, sildenafil, simvastatin, St. John's Wort);
- Use of prescribed systemic or topical medications or any dietary aids or foods that are known to modulate drug metabolizing enzymes (e.g. grapefruit juice) within 14 days of dose administration;
- Difficulty in swallowing oral medications;
- History of seizure disorder;
- Serious psychosocial co-morbidities;
- Cognitive or psychiatric disorders, or any other condition that could interfere with compliance with study procedures and/or confinement in a clinical study unit for 2 days or longer;
- History of drug or alcohol abuse within one year prior to screening;
- Use of any other investigational drug within 1 month prior to enrollment;
- Use of any prescription drugs within 1 month prior to enrollment;
- Use of over the counter medication excluding routine vitamins, but including mega-dose vitamin therapy, within one week of enrollment;
- Donation and/or receipt of any blood or blood products within 3 months prior to enrollment;
- Active gastrointestinal, renal, hepatic, or coagulant disorder within 1 month prior to enrollment;
- Esophageal or gastroduodenal ulceration within 1 month prior to enrollment;
- Hypersensitivity to NSAIDs, sulfonamides, COX-2 inhibitors, or carbonic anhydrase inhibitors;
- Known allergy or hypersensitivity to sulfa drugs;
- Family history of significant cardiac disease (i.e. sudden death in first degree relative; myocardial infarction prior to 50 years old);
- Occult blood in stool (fecal occult blood test).
Key Trial Info
Start Date :
October 1 2008
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2013
Estimated Enrollment :
26 Patients enrolled
Trial Details
Trial ID
NCT00780325
Start Date
October 1 2008
End Date
July 1 2013
Last Update
February 6 2014
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, United States, 19104