E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Randomized multicenter double blind, placebo controlled trial, for the evaluation of the efficacy and tolerability of UDCA on the dissolution of cholesterol gallstones (<15mm) after 18 months of therapy. |
|
MedDRA Classification |
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 |
Evaluation of UDCA efficacy (versus placebo) after 18 months of therapy, in the complete dissolution of radio-lucent cholesterol gallstones with <15mm of greater diameter, occupying less than half the gallbladder area. |
|
E.2.2 | Secondary objectives of the trial |
Evaluation of the incidence of biliary colic episodes, hospitalization and surgery due to acute cholecystitis or acute episode of chronical cholecystitis, biliary lithiasis, choledocho-lithiasis or biliary pancreatitis, in each group Evaluation of maintenance of response (complete stone dissolution) after a 6-month open trial period without therapy. Evaluation of UDCA treatment safety and tolerability, versus placebo.
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Patients from both sexes, in ambulatory, with age equal or greater than 18 years old. 2.Biliary lithiasis diagnosed, with radio-lucent cholesterol gallstones <15mm. 3.At least one previous episode of biliary cholic. 4.Functional gallbladder documented by abdominal echography with Boyden Testing. 5.Patient able to follow the study protocol, according to the investigator’s criteria; 6.Informed consent dated and signed by the patient and the investigator. |
|
E.4 | Principal exclusion criteria |
1.Patient preference for a surgical treatment 2.Planned surgery within the trial duration period 3.More than half the gallbladder area occupied by gallstones. 4.Presence of non-floating gallstones (bilirubin stones). 5.Presence of stones in the main biliary duct 6.Previous treatment with biliary acids 7.Body Mass Index equal or superior to 35 kg/m2 8.Presence of ascitis 9.Total serum bilirubin >2 mg/ dL 10.Aminotransferases or GGT with values greater than 2.5 times the normal value, for periods lasting longer than 1 month (chronic situation) 11.Impaired kidney function (blood creatinin >2 mg/dL) 12.Patients with heart failure grade III or IV (NYHA) 13.Acute heart infarction in the last year, unstable angina pectoris, de novo angina, Prinzemetal angina or severe bradycardia (according to the investigator’s criteria) 14.Patients with progressive degenerative diseases or life-threatening diseases 15.Patients with life expectancy less than 2 years 16.History of intolerance or allergic reaction to the drug being studied, excipients or analogous drugs. 17.Pregnant or breast-feeding women 18.Women of childbearing potential, not using a contraceptive method of recognized efficacy. 19.History of alcohol abuse or drug addiction 20.Any serious clinical or laboratorial modification that according to the investigator may interfere with the evaluation of efficacy or safety or with any of the study procedures.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Complete dissolution of gallstones, incidence of biliary colic, hospitalization and surgery due to acute cholecystitis or acute episode of chronical cholecystitis, biliary lithiasis, choledocho-lithiasis or biliary pancreatitis, in each group. Maintenance of complete stone dissolution after a 6-month open trial period without therapy. Evaluation of UDCA treatment safety and tolerability, versus placebo.
|
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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
|
During the study, patients will be re-evaluated, during the treatment period at 3, 6, 12, and 18 months. After this period, a period of 6 months in open-study will follow, without therapy, for evaluation of the obtained efficacy maintenance. |
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |