Effect of a Combination Oral Formulation of Hyaluronic Acid, Chondroitin Sulphate and Magnesium Trisilicate in Patients With Gastro-Esophageal Reflux Disease Not Fully Satisfied With Their Treatment

Study Overview
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Brief Summary
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This is a post-market, multi-center, double-blind, placebo-controlled, randomized, cross-over study with GERDOff Plus added on top of the current PPI treatment in patients with GERD. The aim of the study is to evaluate the performance of GERDOff Plus, a class III medical device, consisting in a hyaluronic acid, chondroitin sulphate and magnesium trisilicate, in addition to the PPIs, in patients with GERD not fully satisfied with their current treatment with PPIs. Patients will receive either GERDOff Plus or placebo q.i.d. for 21 days followed by a wash-out period of 3 weeks. After the wash-out period, the patients will receive either placebo or GERDOff Plus respectively

Official Title
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Evaluation of the Performance and Safety of an Oral Formulation of Hyaluronic Acid With Chondroitin Sulphate and Magnesium Trisilicate (GERDOff® Plus) in Patients With Gastro-Esophageal Reflux Disease: A Double-blind, Placebo-controlled, Randomized, Cross-over Study

Conditions
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Gastro Esophageal Reflux

Intervention / Treatment
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* Device: Hyaluronic acid with chondroitin sulphate and magnesium trisilicate, 1100 mg melt in mouth tablet
* Device: Placebo 1100 mg, identically-looking melt in mouth tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent (ICF): a written informed consent must be obtained prior to any study related procedure being performed Male and female out-patients aged 18 to 80 years GERD diagnosis confirmed through a validated questionnaire (GERDQ score ≥ 8). EGD endoscopy performed within 1 year before screening Patients in continuous or intermittent treatment with PPI for at least 1 year and continuously for at least 4 weeks prior to study entry Patients not fully satisfied with current PPI treatment (1-3 score on 5-points Likert scale) Exclusion Criteria: Dyspeptic patients or patients with overlapping symptoms with GI diseases other than GERD Histological evidence of Barrett's oesophagus > 1 cm in EGD endoscopy Peptic stricture in EGD endoscopy Concurrent findings in the EGD endoscopy that might interfere with the participation to the study (e.g cancer, peptic ulcer) as judged by the investigator Known impaired kidney or liver function at screening Presence of any relevant severe condition or clinically relevant abnormal parameters that in the opinion of the investigator may interfere with the participation to the study Medication use (including H2 antagonists, alginates, baclofen, NSAIDS, prokinetics, antidepressants) that may interfere with GERD symptom assessment within 2 weeks before the start of the study or during the study Pregnancy or breast-feeding Females of childbearing potential not employing adequate contraceptive methods Active malignancy of any type, or history of a malignancy (patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before study enrolment are also acceptable) History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements Treatment with any investigational drug within the previous 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GERDOff Plus<br>Hyaluronic acid + chondroitin sulphate + magnesium trisilicate melt in mouth tablets (1100 mg). 1 tablet q.i.d. (three after meals, one before resting) for 3 consecutive weeks. After three weeks of wash-out period,patients will take either placebo or GERDOff Plus q.i.d. (three after meals, one before resting) for another three weeks. | Device: Hyaluronic acid with chondroitin sulphate and magnesium trisilicate, 1100 mg melt in mouth tablet<br>* 1 tablet q.i.d. (three after meals, one before resting) for 3 consecutive weeks<br>* Other names: GERDOff Plus;Device: Placebo 1100 mg, identically-looking melt in mouth tablet<br>* 1 tablet q.i.d. (three after meals, one before resting) for 3 consecutive weeks<br>* Other names: GERDOff Plus placebo;|
| Placebo Comparator: Placebo<br>Placebo melt in mouth tablets (1100 mg). 1 tablet q.i.d. (three after meals, one before resting) for three consecutive weeks. After three weeks of wash-out period, patients will take either placebo or GERDOff Plus q.i.d. (three after meals, one before resting) for another three weeks. | Device: Hyaluronic acid with chondroitin sulphate and magnesium trisilicate, 1100 mg melt in mouth tablet<br>* 1 tablet q.i.d. (three after meals, one before resting) for 3 consecutive weeks<br>* Other names: GERDOff Plus;Device: Placebo 1100 mg, identically-looking melt in mouth tablet<br>* 1 tablet q.i.d. (three after meals, one before resting) for 3 consecutive weeks<br>* Other names: GERDOff Plus placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall patient satisfaction | The percentage of patients with an improvement of at least 2 points in the patient satisfaction measured with a 1 to 5 Likert scale (1 worst satisfaction, 5 best satisfaction) | From baseline to the end of the respective 3-week treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of weekly frequency of each symptom using the Gastro Esophageal Reflux Disease Questionnaire (GERDQ) questionnaire | The reduction of weekly frequency score (points) for each symptom (score from 0 to 3, where higher scores mean a worse outcome) assessed by GERDQ questionnaire. Frequency score (points) for symptom: 0=0 day, 1=1 day, 2=2-3 days, 3=4-7 days; How often did you have a burning feeling behind your breastbone (heartburn)? 0 1 2 3 How often did you have stomach contents (liquid or food) moving upwards to your throat or mouth (regurgitation)? 0 1 2 3 How often did you have a pain in the centre of the upper stomach? 3 2 1 0 How often did you have nausea? 3 2 1 0 How often did you have difficulty getting a good night's sleep because of your heartburn and ⁄ or regurgitation? 0 1 2 3 How often did you take additional medication for your heartburn and ⁄ or regurgitation, other than what the physician told you to take? (such as Tums, Rolaids, Maalox?) 0 1 2 3 | From baseline to the end of the respective 3-week treatment period | 
| Change of weekly global score of symptoms using the Gastro Esophageal Reflux Disease Questionnaire (GERDQ) questionnaire | The reduction of global score of GERQ questionnaire (score from 0 to 18, where higher scores mean a worse outcome). Global score is obtained as sum score of the 6 items detailed in Outcome 2. | From baseline to the end of the respective 3-week treatment period | 
| Change of the intensity of each symptom using the Reflux Symptom Index (RSI) questionnaire | The reduction of score of each symptom (from 0 to 5, where 0 = No problem and 5 = Severe Problem) assessed by RSI questionnaire Hoarseness or a problem with voice Cleaning throat Excess throat mucus or postnasal drip Difficulty swallowing food, liquids, or pills Coughing after eating or after lying down Breathing difficulties or chocking episodes Troublesome or annoying cough Sensations of something sticking or a lump in the throat Heartburn, chest pain, indigestion or stomach acid coming up | From baseline to the end of the respective 3-week treatment period | 
| Change of the global score using the Reflux Symptom Index (RSI) questionnaire | The reduction of global score of RSI questionnaire (from 0 to 45, where higher scores mean a worse outcome). Global score is obtained as sum score of the 9 items detailed in Outcome 4. | From baseline to the end of the respective 3-week treatment period | 
| Assessment of palatability | The score of taste through a 4-point qualitative scale (where 1 - taste as bad as possible, and 4 - taste as good as possible) | At the end of 3-week treatment period | 
| Evaluation of the intake of rescue medications | The amount of rescue medications taken | From V1 (randomization) to V4 (Day 63 +/- 2 days) |