Clinical Trials Register

Summary
EudraCT Number:	2014-003174-17
Sponsor's Protocol Code Number:	GA1405
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-28
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

2014-003174-17

A.3

Full title of the trial

A multicentre, randomised, double-blind, two arm, parallel group, placebo controlled pivotal study to assess the effect of a sodium alginate liquid suspension as add-on therapy in GORD patients with inadequate response to once daily proton pump inhibitor treatment.

A.3.1

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

Sodium alginate liquid suspension as add-on therapy in GORD patients with inadequate response to PPI treatment – a pivotal study.

A.3.2

Name or abbreviated title of the trial where available

Sodium alginate liquid suspension as add-on therapy in GORD patients with inadequate response to PPI

A.4.1

Sponsor's protocol code number

GA1405

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) Limited
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) Limited
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	Reckitt Benckiser Healthcare (UK) Limited
B.5.2	Functional name of contact point	Study Specific Mailbox
B.5.3	Address:
B.5.3.1	Street Address	Dansom Lane
B.5.3.2	Town/ city	Hull
B.5.3.3	Post code	HU87DS
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	GA1405@rb.com

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 Liquid Sachets
D.2.1.1.2	Name of the Marketing Authorisation holder	Reckitt Benckiser Healthcare (UK) Limited
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 Liquid Sachets
D.3.4	Pharmaceutical form	Oral suspension in sachet
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.3.8	INN - Proposed INN	SODIUM ALGINATE
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/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIUM HYDROGEN CARBONATE
D.3.9.1	CAS number	144-55-8
D.3.9.3	Other descriptive name	SODIUM HYDROGEN CARBONATE
D.3.9.4	EV Substance Code	SUB12290MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	21.3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CALCIUM CARBONATE
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/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	32.5
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 in sachet
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

Gastro-Oesophageal Reflux Disease (GORD)

E.1.1.1

Medical condition in easily understood language

Gastro-Oesophageal Reflux Disease (GORD)

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 assess the efficacy of sodium alginate liquid suspension 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 are to assess the efficacy of sodium alginate liquid suspension compared with matched placebo liquid in change in duration, frequency, severity 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 a comparison of the treatments with respect to patient satisfaction and safety.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent has been obtained.
2. Age: Minimum 18 years
3. Sex: male or female.
4. Current evidence of symptomatic GORD in accordance with the Montreal definition(5) following treatment with a proton pump inhibitor (as specified in inclusion criteria #6). This evidence can be based solely on symptom characteristics but in the opinion of the Investigator the symptoms are not related to conditions such as irritable bowel syndrome, gall bladder disease or other such conditions that may present themselves as heartburn or regurgitation.
5. Patients must have had troublesome heartburn or regurgitation of at least mild or moderate intensity* on at least 3 days a week during the 2 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:
a. Mild: Awareness of symptom but easily tolerated.
b. Moderate: Discomforting symptom sufficient to cause interference with normal activities including sleep.
c. Severe: Incapacitating symptom with inability to perform normal activities, including sleep.
6. Prescribed treatment with once-daily (before breakfast) PPI for at least the previous 4 weeks at stable standard approved doses, e.g. lansoprazole 30 mg per day, omeprazole 10 to 40 mg per day, pantoprazole 20 to 40 mg per day, 40 mg esomeprazole per day.
7. Compliance regarding use of prescribed once-daily PPI over 4 weeks, as determined by the Investigator.

Following the 7-day run-in period, patients will be assessed against the following inclusion criteria before randomisation.
8.Completion of the run-in diary card and questionnaires on each of the 7 days of the run-in period.
9.At least 3 days during the 7-day run-in period with a HRDQ score [Heartburn and Regurgitation] >0.7.
10.Compliance with PPI treatment (once daily in the morning) on all 7 days of the run-in period.

E.4

Principal exclusion criteria

Patients to whom any of the following conditions apply must be excluded:
1.Oesophageal stricture (diagnostically confirmed), peptic ulcer disease, Zollinger-Ellison syndrome, systemic sclerosis, recent (within the last year) upper gastrointestinal endoscopy examination that has shown LA grade C or D oesophagitis.
2.A recent (previous 3 months) history of drug, solvent or alcohol abuse (weekly alcohol intake ≥140 g or 17.5 units).
3.Recent (previous 3 months) cardiac chest pain.
4.Recent (previous 6 months) significant unexplained weight loss of >6 kg in the last 6 months
5.Gastrointestinal bleeding (lower GI bleeding or haematemesis) within the last 3 months.
6.Patients who have taken non-steroidal anti-inflammatory drugs (NSAIDs, except for low dose aspirin which can be given for cardioprotection) for more than 3 consecutive days in the 28 days prior to screening
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):
a.H2-receptor antagonists
b.Anti-cholinesterase drugs, sucralfate or misoprostol preparations
c.Antacids (including Gaviscon).
8.Patients taking or needing to take macrolide antibiotics, such as erythromycin, azithromycin, from the day before screening.
9.Current enrolment in another study or involvement in a previous study assessing symptom relief with sodium alginate in the past year.
10.Previous surgery of the oesophagus, stomach or duodenum.
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 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 (as defined in Section 10.4).
13.Pregnancy or lactating mother.
14.Patients with known hypophosphataemia, phenylketonuria or hypercalcaemia.
15.Patients with severe/impaired renal function or insufficiency.
16.Any previous history of allergy or known intolerance to any of the Investigational Medicinal Product (IMP) or following formulation constituents: e.g. sodium alginate, parabens (methyl and propyl), hydrogenated glucose syrup (maltitol), 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 whether the patient achieves a reduction of at least 3 days in the number of days with a HRDQ score [Heartburn and Regurgitation]>0.7 during the 7-day treatment period compared to the 7-day run-in period.
The results between the two groups (sodium alginate liquid suspension vs. matched placebo liquid) will be compared.

E.5.1.1

Timepoint(s) of evaluation of this end point

7-day treatment period vs 7-day run-in period

E.5.2

Secondary end point(s)

The following secondary endpoints will be compared between the sodium alginate liquid suspension and matched placebo liquid:

•Change in the mean daily HRDQ score [Heartburn and Regurgitation] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
• •Change in the mean daily frequency/severity of individual symptoms [heartburn and regurgitation taken from HRDQ] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
•The number of nights with symptoms (taken from HRDQ) during the 7-day treatment period.
•Whether the patient has any night-time symptoms (taken from HRDQ) during the 7-day treatment period.
•Change in the mean daily duration of symptoms [taken from HRDQ] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
•The number of symptom-free days (taken from HRDQ) during the 7-day treatment period where patients are free from Heartburn and Regurgitation symptoms.
•Change from baseline in patient satisfaction scores at the end of the study.
•Change from baseline in RDQ symptom scores for the GORD dimension (heartburn and regurgitation) after a 7-day treatment period
•Change in the mean daily score of heartburn and regurgitation [taken from HRDQ] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in) separately.
•Change from baseline in RDQ scores for the heartburn and regurgitation dimensions separately after a 7-day treatment period.
•Change from baseline in frequency/severity scores for the heartburn and regurgitation dimensions [taken from RDQ] separately after a 7-day treatment period.

The daily patient satisfaction score will be assessed against the daily entries in the HRDQ.

Safety will be assessed in terms of the overall proportion of subjects with adverse events (AEs).

Exploratory Endpoints

•Change in the mean daily score of dyspepsia [taken from HRDQ] (mean over the 7 days of treatment) from baseline (mean over the 7 days of run-in).
•Change from baseline in the dyspepsia dimension score [taken from RDQ] after a 7-day treatment period.
•Change from baseline in frequency/severity scores for the dyspepsia dimension [taken from RDQ] after a 7-day treatment period.
•The number of symptom free days (taken from HRDQ) during the 7-day treatment period where patients are free from Heartburn, Regurgitation and Dyspepsia symptoms.

E.5.2.1

Timepoint(s) of evaluation of this end point

7-day treatment period vs 7-day run-in period

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.6

Cross over

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

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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:

272

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

272

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

136

F.4.2

For a multinational trial

F.4.2.1

In the EEA

272

F.4.2.2

In the whole clinical trial

272

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)

Patients who experience AEs at the end of the study, or experience the onset of an AE after the end of the study, will be followed up as described in Sections 13.1.7 and 13.1.8.
No other additional care of study patients will take place following the end of the study. The treatment of the patient’s condition will follow normal clinical practice

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

2014-11-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-12-24

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