Study Of Celecoxib Or Diclofenac And Omeprazole For Gastrointestinal (GI) Safety In High GI Risk Patients With Arthritis

Study Overview
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Brief Summary
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To determine whether celecoxib is superior to combined therapy with diclofenac and omeprazole in the incidence of clinically significant upper and/or lower gastrointestinal (GI) events in high GI risk subjects with osteoarthritis and/or rheumatoid arthritis.

Official Title
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Double-Blind, Triple Dummy, Parallel-Group, Randomized, Six-Month Study To Compare Celecoxib (200 Mg BID) With Diclofenac Sr (75 Mg BID) Plus Omeprazole (20 Mg QD) For Gastrointestinal Events In Subjects With Osteoarthritis And Rheumatoid Arthritis At High-Risk Of Gastrointestinal Adverse Events

Conditions
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Osteoarthritis, Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Celecoxib
* Drug: Diclofenac + Omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a clinical diagnosis of OA or RA and who are expected to require regular anti-inflammatory therapy for arthritis symptom management Subjects must be aged 60 years or older with or without a history of gastroduodenal (GD) ulceration; or be of any age 18 years or older and have had documented evidence of GD ulceration 90 days or more prior to the screening visit Exclusion Criteria: Active GD ulceration or GD ulceration within 90 days of the screening visit. Concomitant use of low dose aspirin Previous MI, stroke or significant vascular disease.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Celecoxib<br>* Participants are assigned to one of two groups in parallel for the duration of the study<br>|
| Active Comparator: B<br> | Drug: Diclofenac + Omeprazole<br>* Participants are assigned to one of two groups in parallel for the duration of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Clinically Significant Upper and/or Lower Gastrointestinal Events (CSULGIEs) | CSULGIE=any of the following: gastroduodenal (GD) hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects were assessed by an independent GI Events Adjudication Committee, who were blinded to study treatment assignments. | 6 month treatment duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With CSULGIES or Symptomatic Ulcers (SUs) | CSULGIE=any of the following: GD hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects with evaluation at an event visit and found to have an ulcer on endoscopy, but did not meet any criteria considered for the primary endpoint by the GI committee were designated as having an SU. | 6 month treatment duration | 
| Change From Baseline in Patient's Global Arthritis Assessment at Month 6/Early Termination (ET) | Subjects rated response to question: Considering all the ways the osteoarthritis or rheumatoid arthritis affects you, how are you doing today? using a 1 to 5 grading scale where 1=very good and 5=very poor. | Month 6/Early Termination (ET) | 
| Number of Subjects With SUs | Subjects with evaluation at an event visit and found to have an ulcer on endoscopy, but did not meet any criteria considered for the primary endpoint by the GI committee were designated as having an SU. | 6 month treatment duration | 
| Number of Subjects With CSULGIEs by History of GD Ulceration | CSULGIE=any of the following: gastroduodenal (GD) hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects were assessed by an independent GI Events Adjudication Committee, who were blinded to study treatment assignments. | 6 month treatment duration | 
| Number of Subjects With Moderate to Severe Abdominal Symptoms | Abdominal symptoms were defined by the Medical Dictionary for Regulatory Activities MedDRA System Organ Class (SOC) 'Gastrointestinal Disorders' and keeping high level group term (HLGT) equal to Gastrointestinal Signs and Symptoms. | 6 month treatment duration | 
| Number of Subjects Withdrawn Due to GI Adverse Events (AEs) | GI AEs were defined using MedDRA SOC Gastrointestinal Disorders but excluding the following HLGTs: Benign Neoplasms Gastrointestinal; Dental and Gingival Conditions; Oral Soft Tissue Conditions; Salivary Gland Conditions; and Tongue Conditions. | 6 month treatment duration | 
| Change From Baseline in Hemoglobin at Month 6/ET |  | Month 6/ET | 
| Change From Baseline in Hematocrit at Month 6/ET |  | Month 6/ET | 
| Number of Subjects With a Clinically Significant Decrease From Baseline in Hematocrit and/or Hemoglobin | A clinically significant decrease from baseline was defined as a fall in hematocrit > = 10 percentage points and/or hemoglobin > = 2 g/dL. | 6 month treatment duration | 
| Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | GGT ULN was 49 international units (IU)/liter (L) for females and 61 IU/L for males, AST ULN was 37 IU/L for females and 39 IU/L for males, and ALT ULN was 43 IU/L for females and 45 IU/L for males. | 6 month treatment duration | 
| Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET |  | Month 6/ET | 
| Change From Baseline in Iron Binding Capacity to Month 6/ET |  | Month 6/ET | 
| Change From Baseline in Ferretin to Month 6/ET |  | Month 6/ET | 
| Change From Baseline in C-Reactive Protein to Month 6/ET |  | Month 6/ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GI events in high risk GI arthritis patients