| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| A single-centre, randomised, four-way crossover study to investigate the measurement of the acid pocket and subsequent gastro-oesophageal reflux episodes using a novel pH/impedance catheter in subjects receiving Gaviscon® Double Action, Gaviscon® Advance and Placebo Liquid versus no treatment. |
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| E.1.1.1 | Medical condition in easily understood language |
| Study to investigate the effect of Gaviscon Double Action and Gaviscon Advance Suspension on the acid pocket and resulting reflux events. |
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| 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 objectives of this study are to assess the formation of the acid pocket, following a high fat test meal, and associated reflux episodes in subjects receiving no treatment and when dosed with Gaviscon® Advance Liquid, Gaviscon® Double Action Liquid or Placebo Liquid. |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Only subjects to whom all of the following conditions apply will be included:
1)Male or female subjects aged ≥ 18 years, ≤ 50 years
2)Subjects who have used over the counter medication to treat for heartburn, typically at least twice per month for the previous 3 months
3)Those whose cigarette consumption is <6 per day and are willing to abstain from smoking while at the study centre
4)Willingness to consume the refluxogenic meal
5)Otherwise healthy subjects, in the opinion of the Investigator
6)Those who are willing to volunteer and have provided written informed consent
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| E.4 | Principal exclusion criteria |
Subjects to whom any of the following conditions apply must be excluded:
1)Those with a history of gastro-oesophageal reflux disease, or reflux symptoms typically requiring self medication with over the counter or prescription medication more than twice a week on an ongoing basis.
2)Those who have a history of active gastrointestinal disease (gastroduodenal ulcer, gastrointestinal haemorrhage, mechanical obstruction or perforation) within the last year.
3)Those who show clinically significant allergic, pulmonary, neurological, renal, hepatic, cardiovascular, psychiatric, metabolic, endocrine, or haematological disease.
4)Those who are observed at screening to have a hiatus hernia with a diameter which exceeds 3cm.
5)Those who have a history of basal skull facture or who have undergone trans-sphenoidal surgery.
6)Those who have been hospitalised within the previous three months for major surgery or medical illness.
7)Those who have had a clinically significant illness within the previous four weeks.
8)Those who have taken any prescription medication or non-prescription medication (other than hormonal contraceptives) within seven days, prior to the screening visit, which the Principal Investigator considers may interfere with the study.
9)Those who have taken H2 antagonists or motility stimulants in the two weeks prior to enrolment in the study and during the study.
10)Those who have taken proton pump inhibitors 4 weeks prior to enrolment into the study and during the study.
11)Any previous history of allergy or known intolerance to any of the study drugs or the following formulation constituents.
12)Those who have a current or recent (one year) history of alcohol abuse or abuse of any legal or illegal drugs, substances, solvents.
13)Those who consume abnormal quantities of coffee, tea or cola (e.g. more than six cups) according to the Principal Investigator’s judgement.
14)Those who have taken part in any clinical study within the previous three months, or have taken part in a total of four or more studies in the last 12 months.
15)Those who are unable to communicate well with the Investigator (i.e. language problem, poor mental development or impaired cerebral function) in the opinion of the Investigator.
16)Those who have evidence of columnar lined oesophagus, or any other significant abnormality in the opinion of the endoscopist and Investigator (as determined during the endoscopy procedure to place the catheter).
17)Woman of childbearing potential, who are pregnant or lactating, seeking pregnancy or failing to take adequate contraceptive precautions. Adequate contraceptive precautions include oral or injectable contraceptives, approved hormonal implants or topical patches, intrauterine devices; barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; true abstinence (true abstinence: when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception. Should the subject become sexually active while participating in the study, she and her partner must agree to use a double barrier method or condoms/diaphragms with spermicidal foam/gel/film/cream/ suppository). Subjects are to be informed verbally that a female condom and male condom should not be used together as friction between the two can result in either product failing. A woman of childbearing potential is defined as any female who is less than 2 years post-menopausal or who has not undergone a hysterectomy or surgical sterilisation, e.g. bilateral tubal ligation, bilateral ovariectomy (oophorectomy).
18)Those previously randomised into this study or those enrolled in the Validation Phase.
19)Those unable in the opinion of the investigator to comply fully with the study requirements.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage of time that the electrode 5 cm above the SCJ is pH < 4 over a period of two hours following treatment with Gaviscon® Double Action Liquid versus Placebo Liquid. |
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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) |
pH change:
1 Percentage of time that the electrode 5 cm above the SCJ is pH < 4 over a period of two hours following treatment with Gaviscon® Double Action Liquid versus the untreated state.
2 Percentage of time that the electrode 5 cm above the SCJ, is pH < 4 over a period of four hours following treatment with Gaviscon® Double Action Liquid versus Placebo Liquid and the untreated state.
3 Percentage of time that the electrode 5 cm above the SCJ, is pH < 4 over a period of two hours following treatment with Gaviscon® Advance versus Placebo Liquid and the untreated state.
4 Percentage of time that the electrode 5 cm above the SCJ, is pH < 4 over a period of four hours following treatment with Gaviscon® Advance versus Placebo Liquid and the untreated state.
5 Percentage of time at each electrode is pH < 4 at 15, 30, 45, 60, 75 and 90 minutes following ingestion of each test product at electrodes 4-11 inclusive.
6 Mean percentage of time with pH < 4 at electrodes 1 2 and 3 during each of the four, one hour periods for Gaviscon® Double Action Liquid, Gaviscon® Advance Liquid versus Placebo Liquid and the untreated state.
7 Mean percentage of time with pH < 4 at electrodes 1-3 during the four hour period for Gaviscon® Double Action Liquid, Gaviscon® Advance Liquid versus Placebo Liquid and the untreated state.
8 Mean percentage of time with pH < 4 at the electrodes within the cardia (electrodes 4-7) during each of the four, one hour periods for Gaviscon® Double Action Liquid, Gaviscon® Advance Liquid versus Placebo Liquid and the untreated state.
Reflux events as identified with impedance monitoring:
9 Total number of (i) liquid, (ii) gas and (iii) mixed reflux episodes occurring in the 2- and 4-hour period following ingestion of Gaviscon® Double Action Liquid, Gaviscon® Advance Liquid versus Placebo Liquid and the untreated state.
10 Total number of (i) acid and (ii) weakly acidic reflux episodes occurring in the 2- and 4-hour period following ingestion of Gaviscon® Double Action Liquid, Gaviscon® Advance Liquid versus Placebo Liquid and the untreated state.
11 Number of reflux episodes reaching 15 cm above the LOS during the 2- and 4-hour period following ingestion of Gaviscon® Double Action Liquid, Gaviscon® Advance Liquid versus Placebo Liquid and the untreated state.
12 Oesophageal bolus exposure to reflux (% time with liquid or mixed reflux within the oesophageal lumen) for each test product versus the untreated state during the 2- and 4-hour period following ingestion of Gaviscon® Double Action Liquid, Gaviscon® Advance Liquid versus Placebo Liquid and the untreated state.
A post hoc correlation of the two data sets (pH and impedance) may be performed following the study. In addition, as this is a pilot study, further exploratory analysis of the data may also occur to develop other relevant secondary endpoints for future studies.
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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 | 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) | 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 | No |
| 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 | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| 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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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
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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 | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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