Clinical Trials Register

Summary
EudraCT Number:	2012-004109-28
Sponsor's Protocol Code Number:	GA1211
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-12-18
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-004109-28

A.3

Full title of the trial

A randomised, 4 way crossover, double blind, placebo controlled pilot study in patients with reflux symptoms, to assess suppression of gastro-oesophageal reflux by ‘Gaviscon Double Action Mint ’ using the Bravo system

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

In this study, Bravo capsules are being used to measure oesophageal pH in order to assess reflux suppression by Gaviscon Double Action Mint

A.4.1

Sponsor's protocol code number

GA1211

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Reckitt Benckiser Healthcare (UK) Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Reckitt Benckiser Healthcare (UK) Ltd
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Gaviscon Double Action Mint
D.2.1.1.2	Name of the Marketing Authorisation holder	Reckitt Benckiser Healthcare (UK) Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Gaviscon Double Action Mint
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	9005-38-3
D.3.9.3	Other descriptive name	SODIUM ALGINATE
D.3.9.4	EV Substance Code	SUB15270MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	144-55-8
D.3.9.3	Other descriptive name	SODIUM BICARBONATE
D.3.9.4	EV Substance Code	SUB12643MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	426
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	471-34-1
D.3.9.3	Other descriptive name	CALCIUM CARBONATE
D.3.9.4	EV Substance Code	SUB13166MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	650
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral suspension
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

This study assesses suppression of gastro-oesophageal reflux of Gaviscon in patients with gastro-oesophageal reflux disease.

E.1.1.1

Medical condition in easily understood language

This study assesses suppression of reflux symptoms (heartburn and acid regurgitation) of Gaviscon in patients with gastro-oesophageal reflux disease.

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

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to compare the effectiveness of Gaviscon Double Action with a matched placebo liquid on the suppression of acid reflux events in patients with reflux symptoms

E.2.2

Secondary objectives of the trial

Secondary objectives are to compare the effectiveness of Gaviscon Double Action Mint versus matched placebo liquid on suppression of acidic and weakly acidic events, oesophageal acid exposure, and clinical benefit in terms of patient reports of reflux symptoms in patients with typical reflux symptoms.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Age: ≥ 18 years ≤ 70 years.
2.Sex: male and female patients.
3.Patients referred to secondary care for further investigation of typical reflux symptoms (heartburn and/or acid regurgitation). Patients must have been referred to secondary care within 2 years of the start of the study. 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. Patients must be symptomatic when withholding prescribed medication for reflux disease.
*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
4.No major esophageal dysmotility (i.e. achalasia, esophageal spasm / hypertensive dysmotility, aperistalsis) or presence of hiatus hernia >3 cm on Oesophageal Manometry or High Resolution Manometry (HiRM)
5.Agreement to withhold acid suppressant PPI and H2 receptor blocking medications and other medications that affect gastro-intestinal function (e.g macrolide antibiotics such as erythromycin and azithromycin, and 5HT agonists such as sumatriptan) for 2 weeks prior to the start of the study and throughout the treatment periods.
6.Agreement to withhold antacids or alginate preparations, except those administered as part of study procedures for 1 day prior to the start of the study and throughout the treatment periods.
7.Patients who give written informed consent.

E.4

Principal exclusion criteria

1.Those with prominent gastrointestinal symptoms or disease other than reflux (including atypical symptoms e.g. cough, sore throat, belching, nausea)
2.Those with difficulty swallowing (dysphagia), gastrointestinal bleeding, weight loss (>5% body weight) or other symptoms suggestive of neoplastic or severe inflammatory disease within the last 12 months.
3.Those with a history or symptoms suggestive of Zollinger-Ellison syndrome, gastric carcinoma, previous or current peptic ulcer disease, pernicious anaemia, Barrett’s oesophagus or systemic sclerosis.
4.Those with a history of upper Gastrointestinal (GI) surgery or endoscopic interventions such as oesophageal dilatations or mucosal resection.
5.Those with known hypophosphataemia.
6.Those with severe constipation or history of colonic stenosis.
7.Those with major oesophageal dysmotility e.g. achalasia, or with hiatus hernia >3 cm on manometry.
8.Those with haematological disorders, bleeding tendency, recurrent nose bleeds or treatment with anti-coagulants (including anti-platelet drugs).
9.Those with physical, neurological or psychiatric conditions preventing repeated visits to hospital or compliance with study procedures (e.g. physical impairment / reduced mobility).
10.Those on a highly restricted salt diet.
11.Those with, or a history of, hypercalcaemia, nephrocalcinosis and recurrent calcium containing renal calculi.
12.Those with clinically abnormal laboratory assessments at screening. Repeat laboratory assessments will not be performed.
13.Female patients 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.
14.Pregnancy or lactating mother.
15.Those who have already participated in the study, including the validation phase.
16.Those who are an employee at the study site.
17.Partner or first-degree relative of the Investigator.
18.Any previous history of allergy or known intolerance to any constituents of the IMP, including: sodium alginate, parabens (methyl and propyl), glucose syrup, carbomer and xanthan gum.
19.Failure to accept or to comply with standard requirements for activity and diet during pH testing as set out in the patient diary.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the number of acid reflux events during the first 24 hour period following treatment with Gaviscon Double Action Mint versus matched placebo liquid.

An acid reflux event is defined as a fall in pH to less than pH 4 with a duration of at least 12 seconds duration (i.e. three consecutive measurements since the Bravo capsule logs pH data every 6 seconds and signal detection recognition requires two consecutive pH measurements at pH<4 to register an acid reflux event).

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 3 and Day 5

E.5.2

Secondary end point(s)

•The combined number of acid reflux events and weakly acid reflux events during a 24 hour period. A reflux event is defined as a fall in pH which is maintained for a duration of at least 12 seconds, where acidic is defined as pH<4 and weakly acidic as between pH 4 and 5.
•The combined number of acid and weakly acidic reflux events in the upright position during a 24 hour period.
•The number of acid reflux events in the upright position during a 24 hour period.
•The number of weakly acidic reflux events in the upright position during a 24 hour period.
•The combined number of acid and weakly acidic reflux events in the supine position during a 24 hour period.
•The number of acid reflux events in the supine position during a 24 hour period.
•The number of weakly acidic reflux events in the supine position during a 24 hour period.
•Oesophageal acid exposure (percentage of time with pH less than pH 4) during a 24 hour period.
•Oesophageal weakly acidic exposure (percentage of time with pH less than pH 5) during a 24 hour period.
•The number, severity and duration of typical reflux symptoms (heartburn, acid regurgitation) documented by study participants in the patient diary card during a 24 hour period.
•The number of typical reflux symptoms (heartburn, acid regurgitation) in the postprandial and night-time periods in the 2hr period after self-administration of the test product.

E.5.2.1

Timepoint(s) of evaluation of this end point

As detailed above

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LVLS

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

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

No other additional care of study subjects will take place following the end of the study. The treatment of the subject's condition will follow normal clinical practice. AEs starting after the end of the study will not be followed up. All suspected adverse reactions reported post-study will be processed in accordance with RB's pharmacovigilance procedures.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-01-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-07-02

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