E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastroesophageal Reflux Disease (GERD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017924 |
E.1.2 | Term | Gastroesophageal reflux |
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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 |
The primary objective of this study is to assess the effect of repeated oral administration of AZD3355, 65 mg bid, measured as reduction in the number of transient lower esophageal sphincter relaxations (TLESRs), compared to placebo during 4 hours post third dose. |
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E.2.2 | Secondary objectives of the trial |
· to assess the number of acid-, weakly acidic- and weakly alkaline reflux episodes and time with esophageal pH<4 by ambulatory impedance-pH measurements · to assess the number of TLESRs, acid-, weakly acidic- and weakly alkaline reflux episodes and time with esophageal pH<4 by combined impedance-pH and manometric measurements · to assess the number of concurrent TLESRs and acid-, weakly acidic- and weakly alkaline reflux episodes · to assess the lower esophageal sphincter (LES) pressure · to assess the effect of AZD3355 on the number of swallows · to study the relationship between total reflux, acid- and non acid (weakly acidic- and weakly alkaline) reflux episodes and GERD symptoms · to assess the pharmacokinetic profile of AZD3355 in GERD patients · to assess the safety and tolerability of AZD3355 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent 2. Male or female (females must be postmenopausal (ie, >12 months without a menstrual period and >50 years of age) or be bilaterally oophorectomized or hysterectomized) 3. Age 18-70 years 4. Weight 60-100 kg 5. At least 6 months history of GERD symptoms (need not to be consecutive) and a history of an incomplete response to PPI treatment 6. Continuously treated with an approved dose of any PPI during at least 6 weeks before enrolment 7. Ability to read and write and to use the e-diary 8. Screening questionnaire (RDQ) indicating a burning feeling behind the breastbone with a frequency of at least 3 days over the past 7 days and with at least mild intensity and/or unpleasant movement of material upwards from the stomach with a frequency of at least 3 days over the past 7 days and with at least mild intensity
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E.4 | Principal exclusion criteria |
1. Screening questionnaire (RDQ) indicating an equal or higher intensity of pain in the centre of the upper stomach than for a burning feeling behind the breastbone, if not fulfilling the inclusion criteria regarding unpleasant movement of material upwards from the stomach 2. History of clinically significant cardiovascular, respiratory, renal, hepatic, neurological, mental or gastrointestinal (excluding GERD) disease. Patients with uncomplicated and well controlled Diabetes Mellitus and patients with uncomplicated and well controlled hypertension (SBP ≤160 mmHg and DBP ≤90 mmHg) can be included 3. S-creatinine >1.2 times upper limit of normal (based on laboratory results from pre-entry visit) 4. History of clinically significant orthostatic reactions 5. Systolic blood pressure below 110 mmHg 6. History of heart disease (eg, ischemic heart disease, congestive heart failure, cardiac arrhythmias) or signs or symptoms of heart disease including QTc >480 ms or other ECG abnormalities 7. Prior surgery of the upper GI tract (open, endoscopic and laparoscopic surgery on the esophagus, the stomach and the duodenum with the exception of over-sewing or endoscopic treatment of a bleeding ulcer). 8. History of severe allergy/hypersensitivity or symptoms/signs of ongoing allergy/hypersensivity 9. Need for concomitant medication with: Drugs that may interfere with the pharmacodynamic effect of Investigational Product (eg, baclofen). Drugs that may influence gastrointestinal symptoms, (eg, H2 receptor antagonists, sucralphate, alginates, tegaserod, metoclopamid, drugs with significant anticholinergic effect, non-steroid anti-inflammatory drugs (NSAIDs), cyclo-oxygenase-2 (COX-2) inhibitors, acetylsalicylic acid (ASA) >160 mg, biphosphonates, antineoplastic drugs) with exception of the PPI and used in the study and antacids Drugs that have a narrow therapeutic window (eg warfarin, digoxin, phenytoin, karbamazepin). Drugs that may prolong the QT interval (see CPSP supplement C for common examples) 10. History of drug addiction, alcohol abuse or other circumstances which in the investigators judgement may compromise the patient’s ability to comply with the study requirements 11. Any other condition which in the opinion of the investigator would render the patient unsuitable for inclusion in the study 12. Blood donation within 4 weeks prior to administration of the first dose of the investigational product 13. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) 14. Administration of any investigational product or participation in any clinical study within 8 weeks prior to administration of the first dose of the investigational product 15. Previous participation in a study with this compound or previous enrolment or randomization of treatment in the present study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to assess the effect of repeated oral administration of AZD3355, 65 mg bid, measured as reduction in the number of transient lower esophageal sphincter relaxations (TLESRs), compared to placebo during 4 hours post third dose. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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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 | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |