A Multicenter, Randomized, Parallel-Group, Active- and Placebo-Controlled, Double- Blind Study Conducted Under In-House Blinding Conditions to Determine the Incidence of Gastroduodenal Ulcers in Patients With Rheumatoid Arthritis After 12 Weeks of Treatment With MK-0966, Naproxen, or Placebo
- Conditions
- -M069-K28M069K28
- Registration Number
- PER-045-99
- Lead Sponsor
- MERCK SHARP & DOHME PERÚ S.R.L.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 0
•Patient is male or female >18 years of age.
•If the patient is female, then she must demonstrate a serum b-hCG level consistent with a nongravid state at the prestudy visit and agree to remain abstinent, use oral birth control pills or single-barrier contraception (one
•partner using condom, diaphragm» contraceptive sponge, or IUD) beginning al least 7 days prior to treatment and continuing at least 14 days after Visit 7.0 or a discontinuation visit. If patient is postmenopausal or status posthysterectomy or tubal ligation, then she is exempt from this requirement. (Postmenopausal is defined as no menses for the previous 1 year. If cessation of menses is within 18 months, follicle-stimulating hormone [FSH] must be documented prestudy as elevated into the postmenopausal range.)
•The patient has a confirmed clinical diagnosis of rheumaioid arthritis and can be expected to require NSAID treatment for at least 3 months.
•Diagnosis of rheumatoid arthritis (RA) occurred at least 6 months prior to the prescreening visit and no earlier than 16 years of age.
•Approved nonstudy anti-rheumatic therapy (including: antimalarials, azathioprine, oral or injectable gold salts, leflunomide, methotrexate, sulfasalazine, oral corticosteroids, or a solubilized TNF antagonist or TNF receptor antagonist) has been at stable dosing for 1 month. Patient must not have discontinued such therapy within 1 month prior to the prescreening visit.
•Patient is willing to avoid excess alcohol for the duration of the study [i.e., will consume no more than 2 drinks (beer 8 oz, wine 4 oz, liquor 1 oz) per day].
•Excepting rheumatoid arthritis, patient is judged to be in otherwise general good health based on medical history, physical examination, and routine laboratory tests.
•In the opinion of the study nurse/coordinator and the investigator, the patient is willing and able to comply with the protocol.
•The patient understands the study procedures and agrees to participate in the study by giving written informed consent.
Previous or Concurrent Diseases
a. Patient is mentally or legally incapacitated» has significant emotional problems at the time of the study, has a history of psychosis, or is unable to give informed consent.
b. Patient has a concurrent medical/arthropathic disease that could confound or interfere with the control of the patient´s symptoms of rheumatoid arthritis with study therapy including, but not limited to:
Systemic lupus erythematosus, spondyloarthropathy, polymyalgia
rheumatica, psoriatic arthritis, ochronosis, pseudogout, or Pagets disease. Note: Patients with a history of gout are allowed to enroll in the study; however, additional NSAID therapy will not be allowed for treatment of exacerbations during the course of the study. Patients with rheumatoid arthritis and secondary Sjogrens disease or fibromyalgia are permitted to enter the study.
c. Patient has a history of esophageal, gastric, biliary, or small intestine surgery (except simple ciosure of a perforation greater than 3 months prior to the study). This includes any gastrointestinal surgery that causes clinical malabsorption.
d. Patients estimated creatinine clearance is less than 30 ml/min or serum creatinine is greater than 2.0 mg/dL.
e. Patient has angina or congesiive heart failure, with symptoms that occur at rest or minimal activity, or has a history of myocardial infarction, coronary angioplasty, or coronary arterial bypass grafting within the past 1 year.
f. Patient has uncontrolled hypertension [Note: Patients with medically controlled hypertension (diastolic blood pressure <95 mm Hg, systolic blood pressure <165 mm Hg) may participate.)
g. Patient has a history of stroke or transient ischemic attack within the past
2 years.
h. Patient has a history of hepatitis/hepatic disease that has been active within the previous 2 years.
i. Patient has a history of neoplastia disease and does not meet one of the exceptions listed below. If the patient has a history of leukemia, lymphoma, or myeloproliferative disease, then he/she is ineligible for the study regardless of the time since treatment, and in such cases, no exceptions will apply.
Exceptions
• Patient has adequately treated basal cell carcinoma or carcinoma in situ of the cervix or in a resected colonic polyp.
• Patient has other malignancies which have been successfully treated for over 5 years prior to screening, where in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of screening.
Patients who, in the joint opinion of the Merck Clinical Monitor and Investigator, are highly unlikely to sustain a recurrence during the duration of the study.
j. Patient has evidence of occult GI bleeding as documented by any one of three stool Hemocult screens obtained and read prior to allocation.
k. Patient has a history of any illness that, in the opinion of the investigator, might confound the results of the study, pose additional risk to the patient, or contraindicate treatment with an NSAID such as naproxen. If there is any question, the Merck Clinical Monitor will be consulted.
1. Patient has a history of inflammatory bowel disease.
m. A gastric, esophageal, and/or duodenal ulcer is present at initial endoscopy, or the patient has endoscopically evident pyloric obstruction or erosive esophagitis.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Endoscopy and fecal occult blood<br>Measure:Incidence of duodenal ulcer<br>Timepoints:Endoscopy: visit 2, visit 5 (week 6), visit 7 (week 12)<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:The esophagus will be inspected as the endoscope is inserted. The mucosa will be graded according to a predefined scale<br>Measure:Esophageal Erosión<br>Timepoints:In the corresponding visits<br>