E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The purpose of this trial is to evaluate the clinical efficacy and safety of an enteric-coated pancreatin tablet in comparison to placebo in the treatment of pancreatic exocrine insufficiency due to chronic pancreatitis. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033628 |
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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 difference between 13C-exhalation (in terms of cumulative percentage of 13C-dose exhaled per hour after 6 hours starting with the end of the test meal) as a marker of lipid digestion and absorption during treatment with verum and placebo. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the difference between the maximum percentage of 13C-dose exhaled per hour within 8 hours during treatment with verum and placebo.
To evaluate the difference between 13C-exhalation (in terms of cumulative percentage of 13C-dose exhaled per hour in 1h-intervals, for 8 hours) during treatment with verum and placebo.
To assess the safety and tolerability of trial medication versus placebo using the following safety parameters: vital signs (blood pressure, pulse rate and body weight measure-ments), number of patients inside and outside the normal ranges of laboratory parameters, physical examinations, ECG and incidence and type of Adverse Events.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients must meet ALL of the following criteria:
1. Male or female, Caucasian, aged 18-75 years. A female of childbearing potential may be enrolled, pro-vided she has a negative pregnancy test at Screening and is routinely using adequate contraception prior to and dur-ing the trial and agrees not to attempt to become pregnant during the trial. A female of non-childbearing potential will be defined as one who has been postmenopausal for at least one year or has been surgically sterilised at least three months prior to the start of the trial or had a hysterectomy.
2. Chronic pancreatitis documented by a score of 4 or more added-up using the following scoring system (modified ac-cording to Layer et al. (1994)): - 4, pancreatic calcification documented by any imaging procedure; - 4, typical histological changes; - 3, characteristic findings on endoscopic retrograde cholangiopancreatography (ERCP) or endosonography; - 2, pancreatic exocrine insufficiency (steatorrhoea by abnormal qualitative or quantitative faecal fat excretion > 7 g/day or abnormal direct function test result (secre-tin-pancreozymin or cholecystokinin test) or pancreo-lauryltest ≤ 20% or faecal elastase 1 test result < 100 µg/g; the result of the latter two tests may be ob-tained during the Screening Phase); - 2, attacks of acute pancreatitis in the anamnesis and/or upper abdominal pain; - 1, diabetes mellitus (disturbed glucose tolerance re-quiring continuous control by diet alone or with the ad-dition of oral agents or insulin).
3. Faecal elastase 1 test result < 100 µg/g faeces at Screen-ing. In case performance of a valid elastase 1 test is not possible due to diarrhoea (defined as more than three doughy faeces per day or watery faeces) a pancreolauryl test will be performed. The result of the pancreolauryl test must be ≤ 20%.
4. Patients with chronic pancreatitis due to alcohol abuse may be included provided they show no clinical symptoms of re-cent alcohol consumption and no alcohol withdrawal symptoms.
5. Patients who, after the nature of the trial and the disclosure of their data has been explained to them, have freely given their Informed Consent in writing.
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E.4 | Principal exclusion criteria |
Patients will be excluded for ANY ONE of the following reasons:
1. Patients with acute pancreatitis or with an acute attack of chronic pancreatitis at Screening or within the last two weeks before Screening.
2. Resection of the head of the pancreas or gastric resection or any operation which destroyed the physiological gastrointestinal junction, e.g. operation according to Y-Roux, Billroth II, Whipple.
3. Any obstructive disease of the biliary tract (e.g. obstructive icterus).
4. Any malignant tumour, e.g. pancreatic carcinoma or recurrence of a malignant tumour within the last 5 years.
5. Other causes for exocrine pancreatic insufficiency than chronic pancreatitis, e.g. cystic fibrosis, primary sclerosing cholangitis, haemochromatosis, isolated enzyme deficiency, deficiency in activation of enzymes in the small intestine.
6. Inflammatory disease of the intestine.
7. History of strictures in the gastrointestinal tract.
8. Peptic ulcer or gastrointestinal bleeding within the last 12 months.
9. Patients with ASAT/SGOT and/or ALAT/SGPT greater than three times the upper limit of the laboratory reference range or any clinically significant laboratory abnormality that in the opinion of the investigator would interfere with the conduct of the study.
10. Bilirubin ≥ 34 µmol/l
11. Albumin ≤ 35 g/l
12. INR ≥ 1.7
13. Patients with a history or clinical evidence of any relevant cardiac, cardio- or cerebrovascular, renal, pulmonary, endocrine, neurologic, infectious, other gastrointestinal, haematological, oncological or psychiatric disease or emotional problems, which, in the opinion of the investigator, would pose a significant risk for the patient, invalidate the giving of Informed Consent or limit the ability of the patients to comply with study requirements or interfere otherwise with the conduct of the study. The same applies for immunocompromised patients and/or neutropenic patients.
14. Patients with a known hypersensitivity and/or contraindication to pork or porcine pancreatin or other components of the study medication or other cross-allergies.
15. Patients unwilling or unable to tolerate discontinuation of their previous pancreatic enzyme substitution (see "Other restrictions").
16. Patients who have donated 450 mL or more blood during the last three months before Screening.
17. Patients who have received an investigational drug within 30 days prior to entering the active treatment phase.
18. Patients who are unwilling or unable to provide Informed Consent or to participate satisfactorily for the entire trial period.
19. Patients taken into custody by court or authorities.
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference between 13C-exhalation (cumulative percentage of 13C-dose exhaled per hour after 6 hours starting with the end of the test meal) as a marker of lipid digestion and absorption during treatment with verum and placebo. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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
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Please refer to the trial protocol, final version 1.0, section 9.3.4. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |