E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastro-Esophageal Reflux Disease |
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E.1.1.1 | Medical condition in easily understood language |
Gastro-Esophageal Reflux Disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017885 |
E.1.2 | Term | Gastrooesophageal reflux disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 determine the effect of vonoprazan compared to esomeprazole for preventing heartburn symptoms over a 4-week treatment period in subjects who have a partial response to treatment with esomeprazole |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of vonoprazan treatment on sustained resolution of heartburn symptoms over a 4-week treatment period (at least one 7-day symptom-free period) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenomics research study and long term storage of samples
Subject eligible for randomization to treatment will be asked to partecipate to an optional study.
At visit 4, Subject that agree to partecipate to this optional study will be asked to sign a separate informed consent form in order to store the remaining DNA sample from the CYP2C19 genotyping and to collect additional blood samples for ribonucleic acid (RNA) isolation.
DNA forms the basis for the genes that make the body produce proteins such as enzymes, drug transporters or drug targets, and may be evaluated for the genetic contribution how the drug is broken down, or how the drug affects the body. This is called a “Pharmacogenomics research study.” Specific purposes of this study include:
- Identifying genetic reasons why certain people respond differently to vonoprazan.
-Finding out more information about how vonoprazan works.
-Generating information needed for research, development, and regulatory approval of tests to predict response to vonoprazan.
- Identifying variations in genes related to the biological target of vonoprazan.
This information may be used, for example, to develop a better understanding of the safety and efficacy of vonoprazan and other study medications, understanding of disease/condition being studied and for improving the efficiency, design and study methods of future research studies |
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E.3 | Principal inclusion criteria |
Subjects will be eligible for participation in the study if they:
-have a documented history of symptoms of both heartburn and acid regurgitation prior to entry into the study
- have a history of persistent heartburn and/or regurgitation symptoms that are troublesome despite an adequate course of PPI treatment;
- continue to have symptoms of heartburn (and regurgitation) following 4 weeks treatment with a high dose of esomeprazole 40 mg QD during the Run-in Period;
- have symptoms of heartburn which increases following a 2-week Washout Period in the presence of regurgitation prior to randomization. Patients with mild (LA grade A) esophagitis are permitted to enter the study. |
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E.4 | Principal exclusion criteria |
- Subjects who have hypersensitivity to vonoprazan or related compounds
- a history or any coexisting diseases affecting the esophagus;
-‘alarm features’ in symptomatology pointing to a possible malignant disease of the GI tract;
- current or historical chest pain due to cardiac disease;
-a history of surgical treatment for GERD;
- dilation of an esophageal stricture or gastric or duodenal surgery.
- Subjects who have a documented history of functional dyspepsia or irritable bowel syndrome or other gastrointestinal diseases which are not acid-related, and therefore, are nonresponsive to gastric acid-blocking treatment.
- Subjects who have levels of AST,ALT or total bilirubin > ULN.
- those who have a documented history of familial adenomatous polyposis, active gastric or duodenal ulcers or acute upper gastrointestinal hemorrhage within 30 days prior to screening and any other co-morbidities or any significant results from physical examinations, or clinical laboratory results as deemed by the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of heartburn-free 24 hour periods (day and night) during 4 weeks of randomized double-blind treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Proportion of subjects with ≥1 sustained resolution of heartburn (defined as ≥7 consecutive days without both daytime and nighttime heartburn any time during the 4-week randomized double-blind Treatment Period). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Single blind during the Run in period |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 4 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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Last patient last follow-up call |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |