E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009093 |
E.1.2 | Term | Chronic pancreatitis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is designed to estimate the dose-response curve for short term efficacy and safety of recombinant microbial lipase (SLV339) in subjects with maldigestion of lipids due to pancreatic exocrine insufficiency (PEI) suffering from chronic pancreatitis (CP). |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria at Visit 1 1. Signed informed consent. 2. Subject must be ≥ 18 years and be of either sex. 3. Pancreatic exocrine insufficiency confirmed and documented in medical history by either a pathophysiological direct or indirect pancreatic function test or Clinical symptoms of steatorrhea stool fat that resolved or improved substantially upon administration of pancreatic enzyme supplementation. 4. Subjects are on a stable daily dose of pancreatic enzyme supplementation for at least 3 months before the start of the study. 5. Subjects with CP with or without partial pancreatectomy due to underlying CP; CP confirmed and documented in medical history by either computed tomography, endoscope retrograde cholangiopancreaticography, plain film with pancreatic calcifications, ultra-sonography (calcifications, duct dilatation), magnetic resonance pancreatography, endoscope ultrasound, other radiological diagnosis captured by tools such as Cambridge classification3 and /or histology. 6. Females of non-childbearing potential (i.e., sterilized via hysterectomy or bilateral tubal ligation or at least 1 year postmenopausal) or if of childbearing potential must agree to practice effective barrier contraceptive methods, use an intrauterine device or use birth control pills or equivalent injectable contraceptive. The subject must have been practicing the selected method of birth control for at least 3 months prior to Visit 1.
Inclusion Criterion at Visit 3 1. Coefficient of fat absorption during the untreated part of the run-in period confirmed as < 80% at Visit 3.
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E.4 | Principal exclusion criteria |
Exclusion Criteria at Visit 1 1. Evidence of cardiovascular, gastrointestinal/ hepatic (except CP or pancreatectomy), renal, neurological/ psychiatric, respiratory, urogenital, hematological/ immunologic, head, ears, eyes, nose or throat, dermatologic/ connective tissue, musculoskeletal, metabolic/ nutritional, drug hypersensitivity, allergy, endocrine (except diabetes mellitus), major surgery (except gall bladder removal or appendectomy) or other relevant diseases as revealed by history, physical examination, and laboratory assessments which might limit participation or completion of the study. 2. Investigational drug intake within 90 days prior to the pre-assessment visit. 3. Gastrointestinal stricture, ileus or acute abdomen. 4. Current excessive intake of alcohol or drug abuse. 5. Allergic disease such as hypersensitivity pneumonitis, Aspergillus mediated asthma or allergic broncho-pulmonary aspergillosis. 6. Allergic reaction to Aspergillus fumigatus (FastCheckPOC®).4 7. Suspected non-compliance or non-cooperation. 8. Stenosis of the esophagus or stomach. 9. Mental disability or any lack of fitness that in the investigator’s opinion precludes the subject’s participation in the study. 10. Human immunodeficiency virus infection in medical history. 11. Subjects requiring treatment with non-permitted medication or exceeding the treatment limits of permitted medication. 12. Subjects in acute phase of pancreatitis. 13. Subjects with the following abnormalities of liver function tests will be excluded: X3 elevation alanine transaminase (ALT) or aspartate transaminase (AST), X2 elevation of bilirubin or subjects with decompensated liver disease. 14. Subjects with impaired renal function: creatinine ≥ 1.7 mg/dl. 15. Subjects with coeliac disease, total gastrectomy, Crohn’s disease and small bowel surgery. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Criteria for Evaluation: Efficacy: Efficacy parameters will be CFA, CNA, stool fat concentration, stool nitrogen, stool weight, nutritional protein and fat intake and clinical symptomatology (stool frequency, stool consistency, abdominal pain, and flatulence). Safety: Safety parameters will include vital signs, physical examination, laboratory and nutritional examinations (triglycerides, cholesterol, low-density-lipoproteins, high-density-lipoproteins, retinol-binding protein, pre-albumin, albumin, transferrin, vitamin E), ADA measurements and adverse events (AEs). |
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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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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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Last subject visit 4 + 30 days |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |