Etoricoxib with naproxen in ankylosing spondylitis

Conditions: Ankylosing Spondylitis (AS)
MedDRA version: 17.0Level: PTClassification code 10002556Term: Ankylosing spondylitisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2010-019872-65-DE

Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 900

Inclusion Criteria

1. Patient is male or female, =18 years of age on the day of signing informed consent.
2. Female patients of reproductive potential must demonstrate a serum ß-hCG level consistent with a nongravid state at the screening visit (Visit 1) and agree to remain abstinent, use oral, barrier, intramuscular, or implanted contraceptives from Visit 1 until 28 days after the last dose of study medication. Women who are postmenopausal or have had a hysterectomy or bilateral tubal ligation or bilateral oophorectomy are exempt from this requirement. Postmenopausal is defined as no menses for the previous 1 year prior to Visit 1; women with cessation of menses within the previous 1 year prior to Visit 1 must have FSH tested at Visit 1.
Note: If a patient’s Visit 1 FSH result is not within the postmenopausal range (as defined by the central laboratory), serum ß-hCG must be tested based on the blood sample from Visit 1 and urine ß-hCG must be tested at Visits 2, 5, 8, and 9 (or discontinuation).
3. Patient has a definite diagnosis of AS per Modified New York Criteria at Visit 1, including at least 1 of the following clinical criteria documented as being present for >=6 months prior to visit 1:
a) low back pain and stiffness which improves with exercise, but is not relieved by rest.
b) limitation of motion of the lumbar spine in both the sagittal and frontal planes.
c) limitation of chest expansion relative to normal values corrected for age and sex.
4. Patient has a history of positive therapeutic benefit with NSAIDs and has taken an
NSAID on a regular basis and at a therapeutic dose level for at least 30 days prior to study enrollment (regular basis is defined as greater than 20 of the previous 30 days, including 7 of the last 10 days).
5. If patient is currently using a non-study AS therapy other than NSAIDs, patient's approved non-study AS therapy has been at stable dosing relative to Visit 2 for the required time periods listed below AND is not anticipated to undergo a change within the first 6 weeks of the protocol. Similarly, patients must not have discontinued such therapy within the timeframe given below:
Adalimumab 3 months
Azathioprine 3 months
Bucillamine 8 weeks
Cyclosporin A 3 months
Etanercept 3 months
Golimumab 3 months
Hydroxychloroquine 8 weeks
Infliximab 3 months
Leflunomide 3 months
Methotrexate 2 months
Pamidronate 3 months
d-Penicillamine 3 months
Sulfasalazine 6 weeks
Thalidomide 3 months
Note: The use of other locally approved AS therapies will be considered on a case-by-case basis and require prior discussion with the SPONSOR (or its delegates) before the patient is enrolled in the study.
6. Patient has a score on BASDAI Question 2 at Visit 1 that is <77mm
7. Patient meets Flare Criteria at Visit 2. Patients are assessed after washout of prestudy NSAID and must satisfy flare criteria before randomization. The minimum and maximum washout duration depends upon the particular prestudy NSAID
Flare Criteria: Patients must demonstrate sufficient flare or worsening of AS pain defined as a score on BASDAI Question 2 at Visit 2 that is:
a) >=40 mm, AND
b) >=30% higher than the BASDAI Question 2 score at Visit 1, AND
c) >=12 mm higher than the BASDAI Question 2 score at Visit 1.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 450
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this

Exclusion Criteria

1. Patient is legally incompetent (e.g., a minor or mentally incapacitated), or has active psychosis, or significant emotional problems at the time of the study which in the view of the investigator are sufficient to interfere with the conduct of the study.
2. Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient/subject to participate.
3. Patient has a concurrent medical/arthritic disease that could confound or interfere with evaluation of efficacy including, but not limited to: Inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis, crystalinduced arthritis, spondyloarthropathy other than AS, DISH (Diffuse idiopathic skeletal hyperostosis)), polymyalgia rheumatica, a history of septic arthritis or intra-articular fracture of the study joint, Wilson’s disease, hemachromomatosis, ochronosis, or primary osteochondromatosis.
4. Patient has acute peripheral articular disease (defined as onset within 4 weeks prior to study) of an active (painful or swollen) peripheral arthritis (note: hip and shoulder are not considered to be peripheral joints).
Note: Patients with a history of chronic peripheral arthritis are permitted to enroll into the study provided that spine pain is the primary source of pain.
5. Patient has a history of gastric or biliary surgery (including gastric bypass surgery), or small intestine surgery that causes clinical malabsorption. Note: Patients who have had gastric banding or patients with cholecystectomy not resulting in malabsorption are allowed to participate.
6. Patient has an active peptic (gastric or duodenal) ulcer or a history of inflammatory bowel disease.
7. Patient has confirmed medical diagnosis of ischemic heart disease, cerebrovascular disease, or peripheral artery occlusive disease. In countries in which the use of COX-2 inhibitors has not been contraindicated in patients with these conditions, patients can otherwise participate (with the exception of those patients who have undergone coronary artery bypass graft surgery, angioplasty, or had a cerebrovascular accident or transient ischemic attack within the past 6 months).
8. Patient has Class II-IV congestive heart failure
9. Patient has uncontrolled hypertension (systolic >160 mm Hg or diastolic > 90 mm Hg) at Visit 1 or Visit 2. Investigators are encouraged to maximize blood pressure control according to local guidelines. Note: Local product labeling should be followed. In countries where the use of etoricoxib is contraindicated in patients with blood pressure values that are persistently elevated above 140/90 mm Hg, this definition of uncontrolled hypertension should be used. Note: Patients may be rescreened one time if blood pressure at Visit 1 is outside of the ranges listed above. Patients must be excluded if blood pressure at Visit 2 is outside of the ranges listed above.
10. Patient has a history of neoplastic disease; Exceptions: (1) patients with adequately treated basal cell carcinoma or carcinoma in situ of the cervix may participate; (2) patients with other malignancies which have been successfully treated = 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