E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pancreatic enzyme replacement therapy is the cornerstone of nutritional management of pancreatic exocrine insufficiency (PEI) due to e.g. cystic fibrosis, chronic pancreatitis, partial or complete pancreatectomy or gastrectomy. Without pancreatic enzyme replacement the patients suffer from severe symptoms of maldigestion as manifested by steatorrhea, abdominal pain, body weight loss etc.
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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 | 10009093 |
E.1.2 | Term | Chronic pancreatitis |
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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 | 10033596 |
E.1.2 | Term | Pancreatectomy |
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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 is to compare the change in CFA of the placebo and pancrelipase groups from baseline (during the single-blind, placebo run-in period) to the end of the randomized, double blind treatment period. |
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of pancrelipase delayed release capsules on CNA (coefficient of nitrogen absorption), stool fat, stool weight, nutritional parameters (triglycerides, LDL cholesterol, HDL cholesterol, retinol-binding proteins, pre-albumin, cholesterol), clinical symptomatology (stool frequency, stool consistency, abdominal pain, flatulence, appetite), Quality of life (QoL) using the SF-36, Body Mass Index (BMI). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Signed Informed Consent
•Age ≥ 18 years
•Chronic pancreatitis or pancreatectomy (total or partial) - Chronic Pancreatitis must be proven (in medical history) by at least one of the following criteria: - Imaging techniques (ultrasound, CT, MRI, or endoscopic ultrasound) - ERCP (endoscopic retrograde cholangiopancreatography) - Plain film of the abdomen with pancreatic calcification - Histology - Pancreatectomy must have occurred more than 180 days prior to enrollment
•Pancreatic exocrine insufficiency has to be proven (in medical history) by either: - pathological direct or indirect pancreatic function tests or - clinical signs of severe steatorrhea, e.g. loose bulky stools or visible stool fat, that resolved upon administration of pancreatic enzyme supplementation or - total pancreatectomy
•Females of child-bearing potential must agree to continue using a medically acceptable method of birth control or agree to abstain from sexual intercourse (abstinence option only with agreement from the local IRB) throughout the study and for thirty days immediately after the last dose of study drug. Medically acceptable methods of birth control are defined as either a bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection (Depo-Provera), an intrauterine device (IUD), or an oral contraceptive that has been taken for at least three months, which the subject agrees to continue using during the study, or a double-barrier method which must consist of a combination of any two of following: diaphragm, cervical cap, condom, or spermicide.
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E.4 | Principal exclusion criteria |
•Evidence of severe cardiovascular, respiratory, urogenital, gastrointestinal/hepatic (except underlying disease), hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatologic/ connective tissue, musculoskeletal, metabolic/nutritional (except underlying disease), endocrine (except diabetes mellitus), neurologic / psychiatric, allergy, recent major surgery (excluding appendectomy and pancreatectomy for CP or abdominal surgery due to underlying disease or gall bladder removal), or other relevant diseases as revealed by history, physical examination and/or laboratory assessments which, might limit participation in or completion of the study.
- Ileus or acute abdomen - Pregnant or lactating females. - Any type of malignancy involving the digestive tract in the last 5 years except pancreatic cancer - Any type of malignancy not in remission - Celiac disease, isolated gastrectomy, Crohn´s disease and small bowel surgery - Presence of pseudo-pancreatic cyst ≥ 4 cm - Continued excessive intake of alcohol or drug abuse - Known allergy to pancreatin or inactive ingredients of Creon - Suspected non-compliance or non-cooperation - Intake of experimental drug within 4 weeks prior to study start - Mental disability or any other lack of fitness, in the investigator's opinion, to preclude subject’s participation in or to complete the study. - Known infection with HIV.
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: The primary efficacy parameter will be the change in CFA from baseline to the end of double blind treatment.
Safety: The safety and tolerability data collected during this study include vital signs, safety laboratory values and adverse events.
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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 | 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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
7 days double-blind, placebo-controlled treatment followed by 6 months of open-label treatment |
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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.8.5.1 | 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 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |