E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Erosive gastro-oesophageal reflux disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017885 |
E.1.2 | Term | Gastrooesophageal reflux disease |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare efficacy (i.e. healing and symptom relief) of Rabeprazole (RAB) Extended-Release (ER) 50 mg versus Esomeprazole (ESO) 40 mg after 4-8 weeks of treatment among subjects with erosive GERD (eGERD), endoscopically confirmed to be Los Angeles (LA) grades C and D at baseline.
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E.2.2 | Secondary objectives of the trial |
To evaluate safety of RAB ER 50 mg associated with 4 to 8 weeks of treatment among subjects with eGERD, endoscopically confirmed to be Los Angeles (LA) grades C and D at baseline. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male or female, ages 18 to 75 years. •History of GERD symptoms (such as acid regurgitation, dyspepsia, chest or epigastric pain) for at least 3 months immediately before screening •Heartburn for at least 2 days a week for at least 1 month before screening •Esophageal erosions of LA grades C or D based on EGD taken within 14 days prior to enrollment •Subjects who are H. Pylori negative based on Urea Breath Test (UBT) •Females should be either of nonchildbearing potential (defined as having undergone surgical sterilization, or postmenopausal [age 50 and amenorrheic for 12 months]) or of childbearing potential. For females of childbearing potential, they must have a negative serum ß-human chorionic gonadotropin (ß-hCG) at Visit 1 and negative urine pregnancy test prior to randomization at Visit 3. Female subjects of childbearing potential must agree to use medically acceptable methods of contraception (e.g., abstinence, or a double-barrier method [e.g., condom + spermicide, condom + diaphragm with spermicide], or intrauterine device, or have a vasectomized partner) starting at Visit 1 and throughout the entire study period and for 1 month after the last dose of study drug. Those women using hormonal contraceptives must also be using an additional approved method of contraception (as described previously) starting at Visit 1 and continuing throughout the entire study period and for 1 month after the last dose of study drug. Pregnant and/or lactating females are excluded. •Subjects must be able to read, write, and understand the language of the symptom diary.
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E.4 | Principal exclusion criteria |
•Subjects who are known to be HIV-positive •Subjects who experience drastic weight loss (>10% total weight) during the 2-month period prior to screening •Use of prescription or non-prescription PPIs or histamine (H2) receptor antagonists within 2 weeks before the screening EGD. •Use of antimicrobials, PPIs or bismuth preparations within 2 weeks before the UBT for H. pylori screening •Use of antacids during the study, except for study-supplied antacid •Current or a history of oesophageal motility disorders (achalasia, scleroderma, or oesophageal spasm) •Current or a history of Barrett's esophagus current oesophageal strictures. Oesophagitis (known or suspected to be due to aetiology other than GERD such as infection, medications). •Current or a history of Zollinger-Ellison syndrome and other acid hyper-secretory conditions, or current gastric or duodenal ulcer. •Current or a history of cancer with the exception of fully excised skin basal cell carcinoma •Inflammatory bowel disease •Unstable diabetes mellitus •History of oesophageal, gastric and duodenal- surgery except simple suturing of an ulcer •Subjects with clinically relevant abnormal laboratory tests at the screening visit, including liver enzymes greater than 2 times the upper limit of normal •Evidence of significant hepatic, renal, respiratory, endocrine, haematologic, neurologic, psychiatric, or cardiovascular system abnormalities, unless the sponsor and investigator agreed that the nature and severity of any abnormality is unlikely to interfere with the conduct of the study, the interpretation of study results, or the health of the subject during the study •Females who are pregnant or lactating •Any condition that would make the subject, in the opinion of the investigator or sponsor, unsuitable for the study •Subjects who have participated in another investigational drug study within 30 days prior to screening or were expected to receive an investigational drug during this trial •Subjects with a history of allergy or sensitivity to any component of Aciphex®, Nexium®, or antacid •Active alcohol and substance abuse •Subjects who were unable or unwilling to give informed consent. •Subjects who were unable or unwilling to complete a daily diary. •Subjects who were unable or unwilling to return for all required study visits. •Subjects who are unable or unwilling to abide by requirements of the study or violate the restrictions of the study as related to prohibited medications (defined in Section 10.6.3) •Subjects with difficulty in swallowing the study medication •Subjects who require daily use of non-steroidal anti-inflammatory drugs (NSAIDs), oral steroids (≥20 mg/day prednisone or equivalent), or aspirin (>325 mg/day).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint #1: the percentage of subjects who achieve endoscopically confirmed healing by 4 weeks after initiation of treatment with RAB ER 50 mg versus ESO 40 mg among subjects with eGERD and with LA grades C and D at baseline.
Superiority will be claimed if the 2-sided p-value is less than 0.05.
If the criteria for superiority are met at week 4, primary endpoint #2 will subsequently be tested.
Primary efficacy endpoint #2: the percentage of subjects who achieve endoscopically confirmed healing by 8 weeks after initiation of treatment with RAB ER 50 mg versus ESO 40 mg among subjects with eGERD and with LA grades C and D at baseline.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study will be date of the last visit of the last patient(s) participating in the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |