Gastrointestinal esophageal reflux disease (GERD) refractory to proton pump inhibitor therapy MedDRA version: 12.1 Level: LLT Classification code 10017885 Term: Gastrooesophageal reflux disease
Conditions
Interventions
Product Name: M0003
Product Code: M0003
Pharmaceutical Form: Tablet
CAS Number: 219984-49-3
Current Sponsor code: M0003
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numb
Sponsors
Shire-Movetis NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria are eligible for this trial: 1. Written ICF signed voluntarily before the first trial-related activity. 2. Aged between 18 and 70 years, extremes included. 3. Subjects with a history of GERD symptoms (i.e., heartburn and/or regurgitation) during the last 6 months (as assessed by anamnesis/medical history). 4. Subjects on a stable dose of PPIs, compliant for at least 6 weeks prior to screening. 5. Subjects with heartburn and/or regurgitation, with at least one of these symptoms of moderate severity or worse, and at a minimum average frequency of three days a week during the two-week run-in period (determined by completion of a daily diary). 6. A minimum of 25 liquid-containing reflux events over 24 h (pH/MII monitoring). 7. BMI =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting one or more of the following criteria cannot be selected: 1. History of cardiac arrhythmias, uncontrolled bronchospastic disease, cardiovascular disease (e.g., ischemic heart disease or cerebrovascular accident), thyrotoxicosis. 2. Subjects with a family history of sudden death or a congenital QT syndrome. 3. Presence of prolonged QTc (Bazett and Fridericia) on ECG at screening (QTc = 450 msec for males and QTc = 470 msec for females). 4. Subjects with a documented history of long segment (>3 cm) Barrett’s oesophagus. 5. Subjects with documented or suspected large (> 3 cm) hiatus hernia. 6. Subjects with fundoplication, endoscopic anti-reflux procedure or major prior GI surgery. 7. Subjects with clinically significant abnormalities as judged by the investigator at screening physical examination, or in blood haematology and biochemistry tests performed at screening. 8. Subjects with a structural abnormality or structural disease condition of the GI tract. 9. Severe oesophageal motility disorders (e.g., scleroderma, achalasia, nutcracker oesophagus). 10. Subjects who suffer from frequent vomiting (>1/week, as assessed during anamnesis). 11. Current diagnosis of co-existing psychiatric disease (including alcohol or drug abuse); controlled depression and anxiety are allowed, when treated with at most one drug, at a stable dose. 12. Subjects suffering from severe and/or uncontrolled endocrine (e.g., insulindependent diabetes mellitus, hypopituitarism, hypothyroidism, hypercalcaemia, pseudohypopara-thyroidism), metabolic (e.g., porphyria, hypokalaemia, amyloidal neuropathy) and neurologic diseases (e.g., Parkinson’s disease, multiple sclerosis, meningocele, aganglionosis, hypoganglionosis, hyperganglionosis, autonomic neuropathy, spinal cord injury, Chagas’ disease, major depression). Endocrine and metabolic disorders controlled by appropriate medical therapy will not be excluded, except for insulin-dependent diabetes mellitus. 13. Presence of severe and clinically uncontrolled cardiovascular, liver or lung disease, neurologic, cancer or AIDS. 14. Alarm symptoms suggestive of malignancies or organic disease such as: obstructive dysphagia, odynophagia, GI bleeding, blood in stool or anaemia, weight loss; unless investigated and found to be negative. 15. Impaired renal function, i.e., serum creatinine concentration >2 mg/dl (>180 µmol/l). 16. Use of prohibited co-medication less than 7 days before the start of the 2-week runin period (baseline symptom assessment). 17. Any condition that, in the opinion of the Investigator(s), would complicate or compromise the trial (e.g., human immunodeficiency virus [HIV] infection, gastroduodenal ulcer) or the well-being of the subject, or evidence of any clinically relevant pathology that could interfere with trial results or put subject safety at risk. 18. Participation in an investigational drug trial in 30 days prior to enrolment. 19. Breast-feeding subjects.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is an exploratory trial : 1. To measure the pharmacodynamic (PD) effect on parameters derived from 24-h pH/impedance (MII) monitoring, 2. To explore the effect on symptoms, 3. To evaluate the safety and tolerability of treatment with 0.5 mg M0003 (on top of PPI treatment), t.i.d. for 4 weeks, in subjects with GERD and with persistent symptoms despite taking a stable dose of proton pump inhibitors ;Secondary Objective: ;Primary end point(s): This is an exploratory trial. • the number of liquid-containing reflux events per 24-h period; • the average proximal extent of all liquid-containing reflux events in the 24-h period; • average bolus clearance times of all liquid-containing reflux events in the 24-h period; | — |
Countries
Belgium, France, Germany, Netherlands, United Kingdom
Outcome results
None listed