E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10064536 |
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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 |
To evaluate the efficacy and safety of two doses of Z-338 in subjects with functional dyspepsia (FD) in order to determine the optimal dosage for Phase III clinical trials |
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E.2.2 | Secondary objectives of the trial |
·To evaluate and identify appropriate primary and secondary efficacy parameters for use in Phase III clinical trials ·To evaluate and identify appropriate inclusion and exclusion criteria for use in Phase III clinical trials ·To assess the safety profile of Z-338 in patients with FD ·To assess relapse rate on weekly basis during 4weeks follow-up period
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects presenting diagnosis of FD as defined by the Rome II Criteria (Gut 1999; 45 [Suppl. 2]: II 37-II 42) - “At least 12 weeks, which need not be consecutive, within the preceding 12 months of: (1) Persistent or recurrent dyspepsia; and (2) No evidence of organic disease (including at upper endoscopy) that is likely to explain the symptoms; and (3) No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool frequency or stool form (i.e. not irritable bowel) (Visit 0 or 1).” 2. Subjects must have consulted for FD problems at least once during the last 12 months prior to study entry (Visit 0 or 1). 3. It should be confirmed that Postprandial fullness and/or Early satiety should be the most bothersome symptom (primary complaint) during the last 14 days prior to eligibility period (Visit 1) by review of the Screening questionniare. 4. Severity of Postprandial fullness, Early satiety, Upper abdominal bloating, Nausea, and Epigastric pain should be at least moderate for at least 2 symptoms including the most bothersome and for 2 days or more per week during the past 14 days prior to eligibility period (Visit 1) by review of the screening questionnaire. 5. Subjects must provide witnessed written informed consent prior to any study procedures being performed (Visit 0 or 1). 6. Subjects must be aged between 18 and 70 years inclusive on the day the Informed Consent is signed (Visit 0 or 1). 7. Male or female subjects. Female subjects of childbearing potential must provide a negative pregnancy test (urine dipstick) at Visit 2, unless surgically sterilised, and must also be using acceptable birth control methods (e.g. contraceptive implant, injectable or patch hormone therapy, oral contraceptives in combination with barrier methods [e.g. condoms], intrauterine device, sexual abstinence, or surgical sterilisation of the subject or the subject’s sexual partner). 8. Subjects must be able to understand the study, comply with the study requirements and return to the investigational site for assessments at specified times. 9. Subjects with a normal upper endoscopy (no ulcers or erosions) within 6 months prior to study entry (Visit 0 or 1) or between Visit 0 and 7 days after Visit 1 (in case a subject has not had an upper endoscopy within 6 months).
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E.4 | Principal exclusion criteria |
1. Subjects who have received treatment with an investigational drug within 28 days prior to study entry (Visit 0 or 1). 2. Subjects with any condition which, in the opinion of the investigator, makes the subject unsuitable for entry into the study (Visit 0 or 1). 3. Females who are pregnant or lactating (Visit 0 or 1). 4. Subjects who have taken proton pump inhibitors (PPIs) within 28 days prior to the eligibility period (Visit 1). Subjects taking PPIs will be asked to discontinue medication and return in 4 weeks for Visit 1 (Visit 0). However, subjects who have taken PPIs for equal to or less than 3 days during the period from 28 days to 15 days prior to eligibility period (Visit 1) may be included in the study. 5. Subjects who have taken drugs that affect gut motility, perception and/or acid secretion: H2- Antagonists, antacids, cisapride, domperidone, metoclopramide, and any other kind of drug, including psychiotrophic or antidepressant agents for treatment, that modify meal accommodation, sensitivity to distension, and/or gastric emptying within 14 days prior to eligibility period (see list of prohibited medications, Appendix X). Subjects taking medications for dyspepsia related symptoms will be asked to discontinue medication and return in 2 weeks for Visit 1 (Visit 0). However subjects who have taken these medications for equal to or less than 3 days during the last 14 days prior to eligibility period (Visit 1) may be includde in the study. Subjects may take one low dose antidepressant but must be stabilised for at least 6 months (see Section 10.6). 6. Subjects with active uncontrolled psychiatric disorders (including those with a major psychosomatic element to their gastrointestinal disease), depression (except at least 6 months stable condition by using one form of medication of standard dose antidepressant, (see above exclusion criteria number 6 and Section 10.6), alcohol or substance abuse in the last 2 years. The antidepressants Amytriptillin and Nortriptillin are always forbidden even if prescribed alone. Subjects taking one and the same medication of anxiolytics, sedatives or hypnotics only once a day for sleep problems are not excluded (Visit 0 or 1). 7. Subjects with known hypersensitivity to gastroprokinetic drugs/agents (Visit 0 or 1). 8. Subjects taking non-steroidal anti-inflammatory drugs (NSAIDs), with the exception of subjects taking prophylactic doses of aspirin for cardiovascular disease (not exceeding 500 mg per day, See Section 10.6) (Visit 0 or 1) 9. Subjects with confirmed organic gastrointestinal disease (Visit 0 or 1). 10. Subjects with former digestive surgery possibly affecting the gastrointestinal motility including endoscopic procedure for gastroesophageal reflux disease [GERD] and obesity. However, subjects with former appendectomy and / or laparoscopic surgery may be included in the study (Visit 0 or 1). 11. Subjects with a significant renal (serum creatinine >2 x upper limit of normal [ULN]), hepatic (alanine transaminase [ALT], aspartate transaminase [AST], gamma glutamyltransferase [GGT], bilirubin >2 x ULN), cardiovascular, pulmonary, endocrine, metabolic or haematological condition (Visit 1). Subjects identified as suffering from serious hepatic dysfunction. 12. Subjects with any evidence of, or treatment for, malignancy (with the exception of basal cell carcinoma) within the last 5 years (Visit 0 or 1). 13. Subjects presenting with primary complaints relieved by stool movements (irritable bowel syndrome [IBS]) (Visit 0 or 1). 14. Subjects who have received Helicobacter pylori (H. pylori) eradication therapy in the 3 months prior to study entry (Visit 0 or 1). 15. Subjects with diabetes (cut off of fasting glucose 120 mg/dL) (Visit 1). 16. Subjects with cardiovascular problems or a history of arrhythmias, or any clinically significant electrocardiogram (ECGs) abnormalities and/or Subjects with any kind of clinical risk of QT-time prolongation. However, subjects who suffer from controlled and non-complicated hypertension may be included (Visit 1). 17. Subjects taking QT-time prolonging drugs such as macrolide antibiotics as well as CYP3A4-inhibiting azole-type antimycotics (see list of prohibited medications, Appendix- X) (Visit 0 or 1) 18. Subjects with body mass index (BMI) over 30 (Visit 1).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of responders to the Global Subject Outcome Assessment at Visit 5 (Week 12).
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 71 |
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 | 2 |
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 | 2 |