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The primary objective of this study is to compare, the number of patients with heartburn and regurgitation symptom resolution after treatment with either rabeprazole 20 mg, esomeprazole 20 mg or esomeprazole 40 mg.
The study is designed to be conducted in a realistic General Practice (GP) setting, enrolling typical Gastro-oesophageal Reflux Disease (GORD) patients that present for treatment, and for whom a Proton Pump Inhibitor (PPI) would normally be prescribed. The study will be conducted over a 4-week period on the basis that current GP standard practice is to treat the GORD patient for a period of 4-weeks prior to reassessment and further follow-up if required. This study is conducted in patients with GORD - associated heartburn (with or without regurgitation) at multiple GP centers, treatment is assigned based on chance (randomized), similar to the toss of a coin and neither doctor or patient knows which treatment they will receive (double-blinded). Following screening to determine eligibility, patients will be randomized to receive oral treatment with either, 20 mg rabeprazole, 20 mg esomeprazole or 40 mg esomeprazole once daily for 4 weeks. This 4-week study encompasses 2 protocol-mandated visits (baseline on day 0 and final visit on day 28). It is hypothesized that rabeprazole 20 mg will be no less effective than (non-inferior) esomeprazole 40 mg for the degree of GORD symptom resolution. Patients will take one tablet (rabeprazole 20 mg or placebo) and one capsule (esomeprazole 20 mg, esomeprazole 40 mg or placebo) each day for 28 days. The study medication will be taken once daily in the morning before breakfast, except the first dose, which will be taken during Visit 1.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 001 | Active Comparator | Esomeprazole 40mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily |
|
| 002 | Active Comparator | Esomeprazole 20mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily |
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| 003 | Active Comparator | Rabeprazole 20mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Esomeprazole | Drug | 20mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily |
| |
| Measure | Description | Time Frame |
|---|---|---|
| The Number of Patients With Complete Resolution of Heartburn by Week 4 | Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe. | week 4 of treatment |
| The Number of Patients Achieving Complete Resolution of Regurgitation Symptoms at Week 4 | Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe. | 4 weeks |
| The Number of Patients Achieving Satisfactory Resolution of Heartburn by Week 4 | Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild) assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe. | 4 weeks |
| The Number of Patients Achieving Satisfactory Resolution of Regurgitation Symptoms by Week 4 | Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild)assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe. | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| The Median Time to Complete Resolution of Heartburn Symptoms. | week 4 of treatment | |
| The Median Time to Complete Relief of Regurgitation Symptoms | 4 weeks | |
| The Mean Percentage of Participants With 24-hour Heartburn Symptom Free Periods |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen-Cilag Pty Ltd Clinical Trial | Janssen-Cilag Pty Ltd | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Belconnen | Australia | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21317257 | Derived | Biscola FT, Abe CM, Guth BE. Determination of adhesin gene sequences in, and biofilm formation by, O157 and non-O157 Shiga toxin-producing Escherichia coli strains isolated from different sources. Appl Environ Microbiol. 2011 Apr;77(7):2201-8. doi: 10.1128/AEM.01920-10. Epub 2011 Feb 11. | |
| 19210493 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rabeprazole 20 mg/Day | Rabeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily |
| FG001 | Esomeprazole 40 mg/Day | Esomeprazole 40 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Rabeprazole |
| Drug |
20mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily |
|
| Esomeprazole | Drug | 40mg once daily for 28days - 1 placebo tab/cap & 1 active tab/cap daily |
|
| 4 weeks |
| Bondi Junction |
| Australia |
| Brookvale | Australia |
| Browns Plains | Australia |
| Campbelltown | Australia |
| Campsie | Australia |
| Caringbah | Australia |
| Castle Hill | Australia |
| Charlestown | Australia |
| Dapto | Australia |
| Darlinghurst | Australia |
| Dubbo | Australia |
| Elizabeth | Australia |
| Fairfield | Australia |
| Hoppers Crossing | Australia |
| Ingleburn | Australia |
| Leichhardt | Australia |
| Maroubra | Australia |
| Melton | Australia |
| Mount Druitt | Australia |
| Oaklands Park | Australia |
| Royal Park | Australia |
| Sydney | Australia |
| Wentworthville | Australia |
| Wyoming | Australia |
| Eggleston A, Katelaris PH, Nandurkar S, Thorpe P, Holtmann G; Treat Study Group. Clinical trial: the treatment of gastro-oesophageal reflux disease in primary care--prospective randomized comparison of rabeprazole 20 mg with esomeprazole 20 and 40 mg. Aliment Pharmacol Ther. 2009 May 1;29(9):967-78. doi: 10.1111/j.1365-2036.2009.03948.x. Epub 2009 Feb 3. |
| FG002 | Esomeprazole 20 mg/Day | Esomeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Rabeprazole 20 mg/Day | Rabeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily |
| BG001 | Esomeprazole 40 mg/Day | Esomeprazole 40 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily |
| BG002 | Esomeprazole 20 mg/Day | Esomeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Number of Patients With Complete Resolution of Heartburn by Week 4 | Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe. | The intent-to-treat (ITT) population was used for all efficacy analyses. The data were reanalysed using the compliance population (defined as all subjects who consumed at least 80% of study medication and who completed at least 80% of data recording). | Posted | Number | participants | week 4 of treatment |
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| Secondary | The Median Time to Complete Resolution of Heartburn Symptoms. | ITT population | Posted | Median | 95% Confidence Interval | days | week 4 of treatment |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | The Median Time to Complete Relief of Regurgitation Symptoms | ITT population | Posted | Median | 95% Confidence Interval | days | 4 weeks |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | The Number of Patients Achieving Complete Resolution of Regurgitation Symptoms at Week 4 | Complete resolution is the absence of symptoms for any 7 consecutive days within the 4 week period assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe. | Posted | Number | participants | 4 weeks |
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | The Number of Patients Achieving Satisfactory Resolution of Heartburn by Week 4 | Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild) assessed by the PAGI-SYM scale. This likert scale describes various symptoms as follows: 0-none, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5-Very Severe. | Symptom scores 0=none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe | Posted | Number | participants | 4 weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | The Number of Patients Achieving Satisfactory Resolution of Regurgitation Symptoms by Week 4 | Satisfactory resolution, which is achieved if, on any 7 consecutive days within the 4 week period, the severity of symptoms never exceeds 'mild' (symptoms must be absent, very mild, or mild)assessed by the PAGI-SYM scale. This likert scale describes a series of symptoms as follows: 0-None, 1-Very Mild, 2-Mild, 3-Moderate, 4-Severe, 5 Very Severe. | Posted | Number | participants | 4 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | The Mean Percentage of Participants With 24-hour Heartburn Symptom Free Periods | Posted | Mean | 95% Confidence Interval | percent of participants | 4 weeks |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rabeprazole 20 mg/Day | Rabeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily | 5 | 464 | 151 | 464 | ||
| EG001 | Esomeprazole 40 mg/Day | Esomeprazole 40 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily | 1 | 469 | 155 | 469 | ||
| EG002 | Esomeprazole 20 mg/Day | Esomeprazole 20 mg once daily for 28 days - 1 placebo tablet/capsule plus 1 active tablet/capsule daily | 9 | 459 | 158 | 459 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| meniscal tear of right knee | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
| |
| cholecystitis | Hepatobiliary disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| lower respiratory tract infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
| |
| pneumonia | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
| |
| alleged assault | Social circumstances | MedDRA 11.0 | Non-systematic Assessment |
| |
| chest pain | General disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| myocardial infarction | Cardiac disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| angina unstable | Cardiac disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| fever | General disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| perianal abscess drainage | Surgical and medical procedures | MedDRA 11.0 | Non-systematic Assessment |
| |
| urinary retention | Renal and urinary disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| multiple pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| depression | Psychiatric disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| vomiting | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
| |
| hypotension | Vascular disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal motility and defaecation cond | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastrointestinal signs and symptoms | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Salivary gland conditions | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Infections - pathogen class unspecified | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Viral infectious disorders | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Other | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Joint disorders | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Muscle disorders | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Musculoskeletal and connective tissue disorders NEC | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Other | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Headaches | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Neurological disorders NEC | Nervous system disorders | MedDRA | Systematic Assessment |
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The MCID of 7.5% was amended to 9% to maintain power with smaller sample size.The proportion of patients without heartburn symptoms at baseline was not evenly distributed between treatment arms. This was a significant predictor of symptom resolution.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Executive Director, Medical & Scientific Affairs | Janssen-Cilag Pty Ltd | +61 2 9815 3219 | mhandel@its.jnj.com |
| ID | Term |
|---|---|
| D005764 | Gastroesophageal Reflux |
| D006356 | Heartburn |
| ID | Term |
|---|---|
| D015154 | Esophageal Motility Disorders |
| D003680 | Deglutition Disorders |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D064098 | Esomeprazole |
| D064750 | Rabeprazole |
| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Male |
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A sample size of 450 subjects per arm will give a 90% power (with a one-sided 95% confidence interval and a minimal clinically important difference of 9%) to demonstrate non-inferiority of rabeprazole 20mg to esomeprazole 40mg with respect to the number of patients with complete resolution of heartburn with or without regurgitation at week 4 |
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