E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Gastro Oesophageal Reflux Disease (GORD) with inadequate response to PPI treatment |
|
E.1.1.1 | Medical condition in easily understood language |
Gastro Oesophageal Reflux Disease (GORD) patients with inadequate response to PPI treatment |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
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 |
The primary objective of this pilot study is to assess the efficacy of Gaviscon® Double Action Mint compared with Matched Placebo Liquid in the suppression of GORD symptoms in patients whose symptoms are inadequately controlled by once daily PPI therapy alone. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this pilot study are to assess the efficacy of Gaviscon® Double Action Mint compared with Matched Placebo Liquid in change in duration, frequency and timing of the symptoms of heartburn, acid regurgitation and dyspepsia in patients with GORD whose symptoms are inadequately controlled by once daily PPI therapy alone. Other secondary objectives include the efficacy of Gaviscon® Double Action Mint compared with Matched Placebo Liquid in subject satisfaction. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent has been obtained.
2. Age: ≥ 18 years.
3. Sex: male or female.
4. Current evidence of symptomatic GORD in accord with the Montreal definition following treatment with a proton pump inhibitor. This evidence can be based solely on symptom characteristics.
5. Patients must have had troublesome heartburn or regurgitation of at least mild or moderate intensity* on at least three days a week during the two weeks before the start of screening. If the patient also has other symptoms, the heartburn or regurgitation must be the predominant symptoms.
*Symptom intensity should be assessed using the following scale;
• Mild: awareness of symptom but easily tolerated
• Moderate: discomforting symptom sufficient to cause interference with normal activities including sleep
• Severe: incapacitating symptom with inability to perform normal activities, including sleep
6. Treatment with once daily PPI for at least the previous 4 weeks at standard doses, eg, lansoprazole 30 mg per day, omeprazole 10 to 40 mg per day, pantoprazole 20 to 40 mg per day.
7. Compliance regarding use of prescribed once-daily PPI over 4 weeks, as determined by the investigator.
8. Status: subjects will be members of the public who respond to an advertisement or letter from the site.
Following the 7-day run in period, patients will be assessed against the following inclusion criteria before randomisation.
1. Completion of the run-in diary card and questionnaires on each of the seven days of the run-in period.
2. At least one reflux symptom (heartburn or regurgitation) of at least mild or moderate intensity measured during the 7-day run-in period (from the HRDQ questionnaire) and a summarised 7-day score of at least 18 (e.g. corresponding to 3 days with moderate heartburn on three occasions per day). (The daily score will be calculated as intensity x frequency, where intensity is scored as 0 = none, 1 = mild, 2 = moderate and 3 = severe and frequency is scored as 0 = none, 1 = once, 2 = twice, 3 = thrice, 4 = 4 or 5 times, 5 = 6 – 10 times and 6 = more than 10 times or constant).
3. Compliance with PPI treatment (once daily in the morning) on all seven days of the run-in period.
|
|
E.4 | Principal exclusion criteria |
1. Oesophageal stricture (diagnostically confirmed), peptic ulcer disease, Zollinger-Ellison syndrome, systemic sclerosis, hiatus hernia (diagnostically confirmed), recent (with last year) upper gastrointestinal endoscopy examination that has shown LA grade C or D oesophagitis.
2. A recent history of drug, solvent or alcohol abuse (weekly alcohol intake ≥ 140g or 17.5 units).
3. Recent cardiac chest pain.
4. Recent, significant unexplained weight loss of greater than 6 kg in the last 6 months.
5. Gastro-intestinal bleeding (hematochezia or hematemesis) within the last 3 months.
6. Non-steroidal anti-inflammatory drugs or other analgesics in doses that might compromise symptom recording.
7. Patients who have taken any of the following treatments in the week prior to the screening visit (Visit 1) and who may require any of these during the study (as they are also excluded throughout the study):
H2-receptor antagonists
Mucous membrane protection drugs
Anti-cholinesterase drugs, sucralfate or misoprostol preparations
Antacids (including Gaviscon)
8. Current enrolment in another study or involvement in a previous symptom relief Gaviscon study in the past year.
9. Previous surgery of the oesophagus, stomach or duodenum.
10. Potential language problems in understanding information and recording symptoms.
11. Any co-existing condition which, in the opinion of the investigator, would be likely to compromise patient safety or interfere with the assessment of efficacy.
12. Female subjects of childbearing potential who, for the duration of the study, are either unwilling or unable to take adequate contraceptive precautions or are unwilling to be sexually abstinent (as defined in Section 10.44).
13. Pregnancy or lactating mother.
14. Subjects with known hypophosphataemia, phenylketonuria or hypercalcaemia
15. Subjects with severe/impaired renal function or insufficiency
16. Any previous history of allergy or known intolerance to any of the Investigational medicinal product’s (IMP) or following formulation constituents: e.g. sodium alginate, parabens (methyl and propyl), glucose syrup, carbomer and xanthan gum.
17. Previously randomised into the study.
18. Employee at study site.
19. Partner or first-degree relative of the Investigator.
20. Participation in a clinical study in the previous 3 months
21. Unable in the opinion of the Investigator to comply fully with the study requirements.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change in HRDQ scores [heartburn and regurgitation only] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The following will be compared between treatments:
• Change in HRDQ scores [dyspepsia only] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
• Change in number of days with night-time symptoms (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
• Change in whether the patient has any night-time symptoms (over the 7 days of treatment) from baseline (over the 7 days of run-in).
• Change in duration of symptoms [taken from HRDQ] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
• Change in frequency of individual symptoms (heartburn, regurgitation, dyspepsia [taken from HRDQ]) (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
• Change in ReQuest™ GI Scores [short version only] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
• Change from baseline in patient satisfaction scores at the end of the study.
• The number of symptom-free days (using both HRDQ and ReQuest™ individually) following one week of treatment with study medication, beginning on day 1.
• Change in number of symptom-free days (using both HRDQ and ReQuest™ individually) (mean over 7 days of treatment) from baseline (mean over 7 days of run-in).
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |