A Two-Part 26-Week Study of Etoricoxib as Treatment for Ankylosing Spondylitis (AS) (MK-0663-108)

Organon

Status and phase: Completed; Phase 3

Conditions: Spondylitis, Ankylosing

Treatments: Drug: Part I - etoricoxib 90 mg; Drug: Part II- Placebo to etoricoxib 60 mg; Drug: Part II- etoricoxib 90 mg; Drug: Part II- naproxen 1000 mg; Drug: Part I - Placebo to etoricoxib 90 mg; Drug: Part II- etoricoxib 60 mg; Drug: Part I - Placebo to naproxen 500 mg; Drug: Part I - etoricoxib 60 mg; Drug: Part II - Placebo to etoricoxib 90 mg; Drug: Part I- naproxen 1000 mg; Drug: Part I - Placebo to etoricoxib 60 mg; Drug: Part II- Placebo to naproxen 500 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01208207

0663-108

Details and patient eligibility

About

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.

Enrollment: 1,015 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,015 participants in 4 patient groups

etoricoxib 60 mg/etoricoxib 60 mg

Experimental group

Description:

The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II

Treatment:

Drug: Part II- Placebo to naproxen 500 mg

Drug: Part II - Placebo to etoricoxib 90 mg

Drug: Part I - etoricoxib 60 mg

Drug: Part I - Placebo to naproxen 500 mg

Drug: Part I - Placebo to etoricoxib 90 mg

Drug: Part II- etoricoxib 60 mg

etoricoxib 60 mg/etoricoxib 90 mg

Experimental group

Description:

The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II

Treatment:

Drug: Part II- Placebo to naproxen 500 mg

Drug: Part II- etoricoxib 90 mg

Drug: Part I - etoricoxib 60 mg

Drug: Part II- Placebo to etoricoxib 60 mg

Drug: Part I - Placebo to naproxen 500 mg

Drug: Part I - Placebo to etoricoxib 90 mg

etoricoxib 90 mg/etoricoxib 90 mg

Experimental group

Description:

The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II

Treatment:

Drug: Part II- Placebo to naproxen 500 mg

Drug: Part I - Placebo to etoricoxib 60 mg

Drug: Part II- etoricoxib 90 mg

Drug: Part II- Placebo to etoricoxib 60 mg

Drug: Part I - Placebo to naproxen 500 mg

Drug: Part I - etoricoxib 90 mg

naproxen 1000 mg/naproxen 1000 mg

Active Comparator group

Description:

The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II

Treatment:

Drug: Part I - Placebo to etoricoxib 60 mg

Drug: Part I- naproxen 1000 mg

Drug: Part II- naproxen 1000 mg

Drug: Part II - Placebo to etoricoxib 90 mg

Drug: Part II- Placebo to etoricoxib 60 mg

Drug: Part I - Placebo to etoricoxib 90 mg