A Two-Part 26-Week Study of Etoricoxib as Treatment for Ankylosing Spondylitis (AS) (MK-0663-108)
Condition: Spondylitis, Ankylosing
MeSH terms: Spondylitis; Spondylarthritis; Spondylitis, Ankylosing
Intervention: Part I - etoricoxib 60 mg; Part I - etoricoxib 90 mg; Part I- naproxen 1000 mg; Part I - Placebo to naproxen 500 mg; Part II- etoricoxib 60 mg; Part II- etoricoxib 90 mg; Part II- naproxen 1000 mg; Part I - Placebo to etoricoxib 60 mg; Part I - Placebo to etoricoxib 90 mg; Part II- Placebo to etoricoxib 60 mg; Part II - Placebo to etoricoxib 90 mg; Part II- Placebo to naproxen 500 mg
Intervention description: etoricoxib 60 mg oral tablet once daily for 6 weeks; etoricoxib 90 mg oral tablet once daily for 6 weeks; naproxen 500 mg oral tablet twice daily for 6 weeks; Placebo to naproxen 500 mg oral tablet twice daily for 6 weeks; etoricoxib 60 mg oral tablet once daily for 20 weeks; etoricoxib 90 mg oral tablet once daily for 20 weeks; naproxen 500 mg oral tablet twice daily for 20 weeks; Placebo to etoricoxib 60 mg oral tablet once daily for 6 weeks.; Placebo to etoricoxib 90 mg oral tablet once daily for 6 weeks.; Placebo to etoricoxib 60 mg oral tablet once daily for 20 weeks.; Placebo to etoricoxib 90 mg oral tablet once daily for 20 weeks.; Placebo to naproxen 500 mg orally twice daily for 20 weeks.
Intervention MeSH terms: Naproxen; Etoricoxib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 1015.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to evaluate the efficacy and tolerability of two doses of
      etoricoxib compared to naproxen in the treatment of ankylosing spondylitis (AS). The primary
      objectives are to evaluate the improvement in Spinal Pain Intensity over 6 weeks of treatment
      with etoricoxib 90 mg or 60 mg compared to naproxen; and to evaluate the improvement in
      Spinal Pain Intensity over 6 weeks of treatment with etoricoxib 90 mg compared with
      etoricoxib 60 mg. Additionally the added benefit of increasing the dose of etoricoxib from 60
      mg to 90 mg will be assessed in the second part of the study. The primary hypothesis is that
      the improvement in Spinal Pain Intensity visual analog scale (VAS) as measured by the
      time-weighted average (TWA) change from baseline over 6 weeks of treatment in Part I for
      etoricoxib 90 mg or 60 mg once daily is not inferior to naproxen 1000 mg.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a definite diagnosis of Ankylosing Spondylitis (AS) per Modified New York Criteria
             made at least 6 months prior to screening

          -  Has a history of positive therapeutic benefit with non-steroidal anti-inflammatory
             drugs (NSAIDs) and regular use of NSAIDS for past 30 days

          -  Has a score on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2
             at screening visit that is <77 mm

          -  Must demonstrate sufficient "flare" or worsening of AS pain

          -  Is in general good health (other than AS)

          -  Has had approved non-study antirheumatic therapy that has been at stable dosing AND is
             not anticipated to undergo a change within the first 6 weeks of the protocol

        Exclusion Criteria:

          -  Has inflammatory arthritis (eg, rheumatoid arthritis, psoriatic arthritis,
             crystal-induced arthritis, spondyloarthropathy, diffuse idiopathic skeletal
             hyperostosis [DISH]), polymyalgia rheumatica, a history of septic arthritis or
             intra-articular fracture of the study joint, Wilson's disease, hemachromatosis,
             ochronosis, or primary osteochondromatosis

          -  Has acute peripheral articular disease (onset within 4 weeks prior to screening) of an
             active (painful or swollen) peripheral arthritis

          -  Has a history of gastric or biliary surgery, or small intestine surgery that causes
             clinical malabsorption

          -  Has had an active peptic (gastric or duodenal) ulcer or history of inflammatory bowel
             disease

          -  Has undergone coronary artery bypass graft surgery (CABG), angioplasty, or has a
             cerebrovascular accident or transient ischemic attack within the past 6 months or has
             active ischemic heart disease, cerebrovascular disease, or peripheral vascular disease

          -  Has Class II-IV congestive heart failure

          -  Has uncontrolled hypertension

          -  Has a history of neoplastic disease, except adequately treated basal cell carcinoma or
             carcinoma in situ of the cervix, or malignancies that have been successfully treated ≥
             5 years prior to screening

          -  Has history of leukemia, lymphoma, malignant melanoma, and myeloproliferative disease

          -  Allergy to etoricoxib or naproxen, or history of a significant clinical or laboratory
             adverse experience associated with etoricoxib or naproxen

          -  Has a history or family history of an inherited or acquired bleeding disorder

          -  Is considered morbidly obese and demonstrates significant health problems stemming
             from obesity, which would confound study participation or interpretation of study
             results

          -  Is pregnant, breast-feeding, or expecting to conceive during the study

          -  Has a clinical diagnosis of hepatic insufficiency defined as Child-Pugh score ≥ 5