Efficacy and Safety Study of HZT-501 in Subjects Requiring Nonsteroidal Anti-Inflammatory Drug (NSAID) Treatment

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether HZT-501 is effective in reducing the rate of development of ibuprofen-associated ulcers in patients who require long-term daily use of ibuprofen.

Detailed Description
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HZT-501 is a combination product including ibuprofen and the acid reducing agent famotidine. The study is designed to determine whether the combination product reduces the rate of ulcer development in subjects who require long-term daily use of ibuprofen. Subjects will be assigned randomly, in approximately a 2:1 ratio, to treatment with either HZT-501 (ibuprofen 800 mg/famotidine 26.6 mg) or ibuprofen (800 mg) three times daily for a 24 week treatment period or until they develop either an endoscopically-diagnosed upper gastrointestinal ulcer and/or prohibitive toxicity. Subjects will visit the study center for Screening and at Weeks 4, 8, 16, and 24. Physical exams will be performed, and clinical laboratory measurements made, at selected times during the study. Endoscopic exams will be performed during Screening and at Weeks 8, 16, and 24. Subjects will be contacted four weeks following study completion.

Official Title
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A Randomized, Double-Blind, Phase 3 Study of the Efficacy and Safety of HZT-501 in Subjects Requiring NSAID Treatment

Conditions
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Ulcer

Intervention / Treatment
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* Drug: Ibuprofen/famotidine
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Expected to require daily administration of an NSAID for at least the coming six months for conditions such as osteoarthritis, rheumatoid arthritis, chronic low back pain, chronic regional pain syndrome, and chronic soft tissue pain. Did not use a NSAID within the 30 days prior to study entry Exclusion Criteria: History of erosive esophagitis History of any of the following serious gastrointestinal complications: perforation of ulcers, gastric outlet obstruction due to ulcers, or gastrointestinal bleeding. Active cardiac, renal, and/or hepatic disease Current Helicobacter pylori (H. pylori) infection Use of an acid suppressant agent, misoprostol, or more than 325 mg/day of aspirin within the 14 days prior to study entry. Uncontrolled diabetes Uncontrolled hypertension Positive pregnancy test at screening Positive test at Screening for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Currently participating, or participation within 30 days prior to study entry, in an investigational drug study Please note that there are other additional criteria. The study center will determine if patients meet all of the criteria.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>HZT-501: Ibuprofen 800mg/famotidine 26.6mg | Drug: Ibuprofen/famotidine<br>* HZT-501: Ibuprofen800mg/famotidine 26.6mg administered orally 3 times daily for 24 weeks<br>|
| Active Comparator: 2<br>Ibuprofen 800mg | Drug: Ibuprofen<br>* Ibuprofen 800mg administered orally 3 times daily for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Develop Endoscopically-diagnosed Gastric Ulcers | The primary efficacy endpoint was the number of participants with gastric ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Develop Endoscopically-diagnosed Upper Gastrointestinal (UGI) Ulcers During the 24-week Treatment Period. | The secondary efficacy endpoint was the number of participants with UGI (i.e., gastric and/or duodenal) ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. | 24 weeks | 
| Number of Participants Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period. | The secondary efficacy endpoint was the number of participants with duodenal ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. | 24 weeks | 
| The Number of Participants Developing Non-steroidal Anti-inflammatory (NSAID)Associated Serious Gastrointestinal Complications (Perforation of Ulcers, Gastric Outlet Obstruction Due to Ulcers, Gastrointestinal Bleeding) | The secondary efficacy endpoint was the number of participants developing a NSAID-associated serious gastrointestinal complication at any time throughout 24 weeks of treatment. A NSAID-associated serious gastrointestinal complication was defined as a perforation of ulcers, gastric outlet obstruction due to ulcers, and/or gastrointestinal bleeding. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ibuprofen, famotidine, ulcers, NSAIDS, pain, arthritis, chronic regional pain syndrome, chronic soft tissue pain, osteoarthritis, rheumatoid arthritis, chronic low back pain