A Study to Evaluate the Clinical Benefits of Tramadol/Acetaminophen (Ultracet) Versus Diclofenac in the Treatment of Pain in Patients With Ankylosing Spondylitis Receiving Stable Treatment of Disease Modifying Anti-rheumatic Drugs (DMARDs)

The purpose of the study is to investigate the clinical benefit of Tramadol/Acetaminophen (Ultracet) vs. NSAID (Diclofenac 50 mg) in the treatment of pain in patients with ankylosing spondylitis receiving stable treatment of disease modifying anti-rheumatic drugs (DMARDs).

This study is a single center, open labeled, randomized, parallel group trial to compare the effectiveness (pain relief) and safety of tramadol 37.5 mg and acetaminophen 325 mg (Ultracet) with Diclofenac in patients with ankylosing spondylitis receiving stable treatment of disease modifying anti-rheumatic drugs (DMARDs). Patients who meet the entry criteria will be randomized to one of the two treatment groups (Ultracet and Diclofenac). One group will treated with Tramadol 37.5 mg/Acetaminophen 325 mg combination tablet and another group will treated with Diclofenac 50 mg tablet. Patients randomized into this study will be instructed to take the one tablet Ultracet or Diclofenac 50 mg by mouth twice a day for 8 weeks. Evaluations will be performed as outlined: at screening, at baseline, and at weeks 2, 4, and 8. Non-steroidal anti-inflammatory drugs (NSAID) therapy with drugs such as indomethacin or more recently COX-2 inhibitors, are used to control the inflammation and pain in patients with ankylosing spondylitis. However, long-term usage of NSAIDs, including COX-2 inhibitors, are known to have gastrointestinal and possible cardiovascular toxic effects, which could restrict their use. Tramadol is a centrally acting analgesic compound. Acetaminophen is another centrally acting analgesic. The primary endpoint is to compare the mean change from baseline in VAS pain score between the two treatment groups (Ultracet vs Diclofenac). Other endpoints include (1) to compare the Bath AS Functional Index (BASFI) and its independent components, (2) to compare the Bath AS Disease Activity Index (BASDAI) and its independent components, and (3) to evaluate the quality of life by SF-36 and its components. The safety of Ultracet and Diclofenac in this patient population by analyzing safety data in terms of adverse events and laboratory values. Experimental Group will treated with Ultracet (Tramadol 37.5 mg/Acetaminophen 325 mg combination tablet). Control Group will treated with Diclofenac 50 mg tablet. Patients randomized into this study will be instructed to take the one tablet Ultracet or Diclofenac 50 mg twice a day for 8 weeks.

• Ankylosing Spondylitis
• Pain

Inclusion Criteria:

• Diagnosis of AS, as defined by Modified New York Criteria for Ankylosing Spondylitis
• Low-back pain of at least 3 months duration improved by exercise and not relieved by rest
• Limitation of lumbar spine in sagittal and frontal planes
• Chest expansion decreased relative to normal values for age and sex
• Bilateral sacroiliitis, grade 2-4 or Unilateral sacroiliitis, grade 3-4 (Stoke)
• Patients are suffering from pain, with VAS pain score >=40 mm
• Patients Between 18 and 70 years of age
• Patients are receiving disease modifying anti-rheumatic drugs (DMARDs), which have reached to the stable dosage within 4 weeks prior to the randomization visit
• Serum creatinine <=1.2 mg/dl
• Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) <= 3 times the laboratory's upper limit of normal
• ESR (Erythrocyte Sedimentation Rate) <= 28mm/hour and CRP (C- Reactive Protein) <=0.8mg/L
• Willingness and capability to give written informed consent, written consent for data protection, willingness to participate, and to comply with the study.

Exclusion Criteria:

• Had an inadequate response to Tramadol HCl therapy, or have discontinued Tramadol HCl therapy due to adverse events
• Have taken Tramadol HCl within 4 weeks prior to the entry of the study
• Have taken other medications for pain relief within 4 weeks prior to the entry of the study, except rescue medications
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease (e.g. heart failure class III/IV NYHA, cardiac infarct within last 6 month), nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders
• Patients with a history of a severe psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study
• Other major medical situations not suitable for the study judged by investigator's evaluation
• Women with pregnancy or breast-feeding
• Hepatitis B or C.