E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastroesophagal Reflux Disease |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018203 |
E.1.2 | Term | GERD |
|
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 |
To evaluate the efficacy of three different doses of ADX10059 compared with placebo when administered twice daily for 4 consecutive weeks on breakthrough symptoms of GERD (heartburn and / or regurgitation) in patients with GERD who are partial responders to PPI treatment. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effects of three different doses of ADX10059 compared with placebo on: heartburn, regurgitation, sleep disturbance due to GERD, occurrence of nocturnal GERD, occurrence of post-prandial GERD, patient and investigator global assessment of study medication, requirement for antacid medication, Patient Assessment of Upper Gastrointestinal Disorders Symptoms Questionnaire PAGI-SYM and Hospital Anxiety and Depression Score (HADS) • To evaluate the safety and tolerability after repeated administration of ADX10059 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient will be invited to participate if he/she meets the following inclusion criteria: 1. is willing and able to provide written informed consent 2. is male or female and aged 18 to 70 years, inclusive 3. is diagnosed with typical GERD and is a partial responder to a stable “standard clinical symptom control” dose of PPI therapy. A partial responder is defined as a patient who experiences symptom improvement on PPI treatment but who has residual moderate or severe typical symptoms (heartburn or regurgitation) on at least 2 days / week but no more than 5 days / week whilst on their standard PPI dose (defined as the indicated dose for the treatment of clinical symptoms), as confirmed from the eDiary data recorded on Days -8 to -2 inclusive 4. has a body mass index (BMI) of ≤32 kg/m2 5. has an ability to communicate well with the study staff and to comply with the requirements of the entire study including compliance with eDiary completion |
|
E.4 | Principal exclusion criteria |
A patient will be excluded from study participation if he/she meets any of the following criteria: 1. has exclusively atypical symptoms of GERD, such as coughing, sore throat, respiratory symptoms etc. (i.e. atypical symptoms in the absence of heartburn and / or regurgitation) 2. has symptoms that have been shown not to be associated with GERD, acid or non-acid 3. has a history of erosive oesophagitis as demonstrated by endoscopy within the previous 12 months of Grade B or worse (Los Angeles classification grading score) 4. has been treated or is currently treated with a dose of PPI greater than the dose indicated for clinical symptom control of GERD 5. has a documented history of hiatus hernia > 3 cm 6. has a current diagnosis of co-existing psychiatric disease that, according to the investigator, could interfere with the conduct of the study 7. has a known clinically significant allergy or known hypersensitivity to drugs that, in the opinion of the investigator, may affect the patient’s safety 8. has clinically significant abnormal laboratory parameters at Screening, in particular, liver or renal functions tests greater than twice the upper limit of normal (ULN) or any other clinically significant biochemical or haematological abnormality as determined by the investigator 9. has known or suspected human immunodeficiency virus (HIV) or hepatitis B or C 10. is pregnant or breast-feeding. Female patients who are of child-bearing potential must be using adequate contraceptive methods with a low failure rate of less than 1% per year (e.g. oral contraceptive, some intra-uterine devices, intra-muscular hormonal contraceptive), and have a negative pregnancy test at Screening and prior to randomisation on Day -1 11. is an habitual user of recreational drugs (including amphetamine, methamphetamine, cocaine and opiates), and who has used them within 14 days prior to Screening or has a positive test for drugs of abuse at Screening 12. has received sodium valproate or topiramate within 30 days of Screening 13. has a history of a significant medical condition that may affect the safety of the patient or preclude adequate participation in the study, including but not limited to coronary artery disease, chronic obstructive pulmonary disease, arrhythmias, diabetes and epilepsy 14. has received any investigational drug within 30 days of Screening |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: The number of GERD symptom (heartburn and/or regurgitation) free days in week 4 of study medication adjusted for baseline will be evaluated. Baseline is defined as the last 7 days prior to randomisation (Day -8 to -2). |
|
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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
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 | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
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
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
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 | 1 |