E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with pancreatic exocrine insufficiency (PEI) secondary to type 1 diabetes mellitus (DM) |
Pacientes con insuficiencia pancreática exocrina (IPE) secundaria a diabetes mellitus (DM) tipo 1 |
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E.1.1.1 | Medical condition in easily understood language |
Patients with type 1 diabetes mellitus and maldigestion |
Pacientes con diabetes mellitus tipo 1 y maldigestión |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
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 |
To demonstrate the superior efficacy of pancreatic enzymes over placebo in improving digestion in subjects suffering from PEI secondary to type 1 DM. The primary efficacy parameter will be the change in the 13C-cumulative recovery rate (CRR) from baseline to treatment as evaluated by the 13C-MTG breath test |
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E.2.2 | Secondary objectives of the trial |
1. To investigate the prevalence of PEI in patients with type 1 DM and the potential factors associated with PEI, among them age, gender, years of disease, alcohol intake, smoking, BMI, presence of glutamic acid decarboxylase antibody (GAD) or insulinoma-associated protein 2 (IA2), diabetic control as evaluated by the circulating levels of HbA1C, frequency of ketoacidosis and hypoglycemic events, daily insulin dose requirements, and presence of neuropathy and vascular disease (retinopathy, nephropathy). 2. To evaluate the effect of PERT compared to placebo on glycemic control (HbA1C), abdominal symptoms (abdominal pain, distention and discomfort, postprandial fullness, early satiety, meteorism, bloating, stool frequency and consistency, flatulence), quality of life (QoL SF-36) and nutritional status (hematologic and biochemical nutritional parameters). 3. To evaluate the safety and tolerability of PERT in type 1 DM, including vital signs, safety laboratory values and adverse events. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients older than 18 with type 1 DM as defined according to the ADA guidelines (see below). • Written informed consent. • After visit 1: Presence of two or more abnormal hematological and/or biochemical nutritional parameters. • After visit 2: PEI diagnosed by the 13C-MTG breath test and defined as a 13C-CCR <29%. |
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E.4 | Principal exclusion criteria |
• Age < 18 years. • Pregnancy or lactancy. • Unwillingness or inability to understand the study and sign the consent, or to accomplish with the visits and procedures of the study. • Diagnosis of chronic pancreatitis, pancreatic cancer or any other disease or condition potentially associated with PEI. • Previous gastrointestinal surgery other than appendectomy and cholecystectomy. • Any kind of uncured malignant disease. • Known allergy to products of porcine origin. • Need of any therapy known to influence pancreatic secretion (e.g. somatostatin and somatostatin analogues). • Severe gastroparesia leading to frequent vomiting and malnourishment. • Intake of any experimental drug within 4 weeks before entry into the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in fat digestion as measured by the 13C-MTG breath test (13C-CCR) from basal to therapy (PERT or placebo). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Prevalence of PEI in patients with DM type 1, difference in glycemic control, symptoms, QoL and nutritional status between PERT and placebo at month 1 (symptoms), 3 and 6 after randomization. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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Severe adverse events cosidered to be related to the study drug. Major protocol violation |
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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 | |