Gastro-protective Effect and Pain Relief Effect of Naxozol Compared to Celecoxib in Patients With Osteoarthritis

Study Overview
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Brief Summary
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Naxozol is a combination product of naproxen, a non-steroidal anti-inflammatory drug (NSAID) and esomeprazole, a proton pump inhibitor which is designed to improve symptoms and reduce risk of gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers in the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The purpose of this study is to investigate whether naxozol protects the gastrointestinal tract effectively compared to celecoxib, a COX-2 inhibitor.

Detailed Description
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A total of 10 orthopedic investigators will participate in this study. The effectiveness in gastro-protection of study drug will be assessed by Leeds Dyspepsia Questionnaire (LDQ). The orthopedic investigators will be trained with this questionnaire administration by an expert gastroenterologist prior to starting this study.

Official Title
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A Prospective, Randomized, Double-blinded, Double-dummy, Active-controlled, Multi-center, Interventional Study to Compare Gastro-protective Effect and Pain Relief Effect of Naxozol Compared to Celecoxib in Patients With Osteoarthritis

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Naproxen/Esomeprazol 500/20mg
* Drug: Celecoxib 200mg
* Drug: Naxozol-Placebo
* Drug: Comparator-Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Koreans given informed consent Patients who have ability of reading comprehension and completing questionnaires (EQ-5D and VAS)and have willingness to follow-up 12 weeks Patients with osteoarthritis symptoms confirmed by his/her medical history and with pain-VAS of 40 and more Exclusion Criteria: Patients who participate into other interventional study or had participated within 30 days before screening Alcohol or drug abuse within 6 months or alcohol consumption of 21 units and more in a week Peptic ulcers accompanied with a complication such as bleeding, perforation, penetration or gastric outlet obstruction within 5 years, or a history of active peptic ulcer or peptic ulcer without a complication within 6 months at screening Patients who are known with Helicobacter pylori infection but have not received any bacteriostatic treatment Known gastroesophageal reflux disease (GERD) Any following joint diseases which may significant effect to the efficacy and safety assessments: septic arthritis, inflammatory joint arthritis such as rheumatoid arthritis, gout, recurrent pseudo-pain, Paget's disease, joint fracture, joint ochronosis, acromegaly, hematochromatosis, Wilson's disease, primary osteochondrosis, Ehlers Danlos Syndrome, or other collagen genetic disorder Patients who are scheduled admissions to hospital for elective surgery during this study History of gastrointestinal cancer Gastrointestinal disorders related to drug malabsorption Gastrointestinal bleeding, cerebral bleeding, other bleeding disorders, or severe hematological disorders Clinically significant diseases such as moderate or severe liver diseases (Child Pough Class II or more), severe heart failure or a history of coronary artery bypass graft (CABG), severe kidney diseases (CrCl<30ml/min) Know allergy experiences with any ingredient of study drugs or with other NASIDs or protocol pump inhibitors (PPIs) Patients who had had a joint surgery for osteoarthritis within 1 year Women of childbearing potential who do not agree with clinically appropriate contraception during this study

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Group<br>Naproxen/Esomeprazol 500/20mg and Comparator-Placebo for 12 weeks | Drug: Naproxen/Esomeprazol 500/20mg<br>* Tablet, b.i.d.<br>* Other names: Naxozol;Drug: Comparator-Placebo<br>* Capsule (which is identical to Celebrex), o.d.<br>|
| Active Comparator: Comparator Group<br>Celecoxib 200mg and Naxozol-Placebo for 12 weeks | Drug: Celecoxib 200mg<br>* Capsule, o.d.<br>* Other names: Celebrex;Drug: Naxozol-Placebo<br>* Tablet (which is identical to Naxozol), b.i.d.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leads Dyspepsia Questionnaire (LDQ) Change | Mean change from baseline of Leads Dyspepsia Questionnaire | Baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean LDQ | Mean value of Leads Dyspepsia Questionnaire at 12 weeks | Baseline, 12 weeks | 
| Gastrointestinal Symptom Rating Scale (GSRS) Change | Mean change from baseline of Gastrointestinal Symptom Rating Scale | Baseline, 12 weeks | 
| Gastrointestinal Adverse Events Rate | Dyspepsia, Diarrhoea, Nausea, Abdominal Pain, Heartburn | Baseline, 12 weeks | 
| Drug Discontinuation Rate Due to Gastrointestinal Adverse Events |  | Baseline, 12 weeks | 
| Pain Relief Effect, mean change from baseline of Pain Visual Analogue Scale (VAS) | Mean change from baseline of Pain Visual Analogue Scale (VAS) | Baseline, 12 weeks | 
| Quality of Life Change, mean change from baseline of EQ-5D | Mean change from baseline of EQ-5D | Baseline, 12 weeks | 
| Treatment Compliance | Non-compliance is defined less than 80% | Baseline, 12 weeks | 
| Rescue Drugs Usage | Acetaminophen ER 650mg and/or Almagate 500mg will be administrated for control of severe pain events and/or of severe gastrointestinal events. | Baseline, 12 weeks | 
| Adverse Events | Adverse Events and Abnormalities from Vital Signs, Physical Exam, and Clinical Laboratories | Baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Naxozol, LDQ, GSRS, Osteoarthritis, Gastroprotective