E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent acute pancreatitis |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent acute inflammation of the pancreas |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033647 |
E.1.2 | Term | Pancreatitis acute |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
In outpatients with recurrent acute pancreatitis it will be investigated whether 12 months treatment with oral naldemedine will significantly reduce the number of pancreatitis attacks as compared to placebo. |
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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 |
• Signed informed consent before any study specific procedures • Able to read and understand Danish or Swedish (depending on site) • Male or female age between 18 and 74 years • At least one attack of non-biliary AP (as defined by the revised Atlanta criteria ) within the last 12 months and at least two attacks within 5 years • The researcher believes that the participant understands what the study entails, is capable of following instructions, can attend when needed, and is expected to complete the study • The investigator will ensure that fertile female participants have a negative pregnancy test before treatment initiation and use contraception during the study period. The following methods of contraception, if properly used, are generally considered reliable: oral contraceptives, patch contraceptives, injection contraceptives, vaginal contraceptive ring, intrauterine device, surgical sterilization (bilateral tubal ligation), vasectomized partner, double barrier (condom and pessary), or sexual abstinence. Methods of contraception will be documented in the source documents • Clinically stable at time of inclusion |
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E.4 | Principal exclusion criteria |
• Known allergy towards study medication • Known or suspected major stenosis or perforation of the intestines • Known or suspected abdominal cancer (incl. intestine, pancreas and the biliary tree) • Pre-existing renal insufficiency (defined as habitual eGFR below 45) • Female participants that are lactating • Severe pre-existing comorbidities (assessed by investigator upon inclusion) • Attack of AP requiring admission within four weeks prior to inclusion • Gallstone etiology of RAP (MRCP or endoscopic ultrasound excluding biliary etiology of AP must be available prior to enrolment as part of the protocol) • Treatment with potent CYP3A4-inhibitors (ketoconazol, itraconzol, ritonavir) or P-gp inhibitors such (e.g. cyclosporine). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Individual difference in number of AP attacks verified by the Atlanta criteria between the naldemedine group and the placebo group during the 12-month treatment period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monthly telephone interviews (Month 1-12) and end of study visit after 12 months |
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E.5.2 | Secondary end point(s) |
1b. Difference in number and severity (assessed by questionnaires) of pain attacks (without fulfilling AP criteria) between subgroups during the 12-month treatment period 2b Difference in gut function assessed with the Bristol Stool Form Scale and Gastrointestinal Symptom Rating Scale between subgroups from baseline to 12 months follow-up 3b. Difference in pancreatic morphology (pancreas volume/size, fibrosis, fatty infiltration, and ductal pathology) between subgroups, measured by MRI, from baseline to 12 months follow-up 4b. Difference in exocrine and endocrine pancreas function between subgroups, assessed by fecal-elastase test and hemoglobinA1c (HbA1c), from baseline to 12 months follow-up 5b. Difference between subgroups in quality of life and patient’s global impression of change, assessed by questionnaires, from baseline to 12 months follow-up 6b. Difference between subgroups in health resource utilization (i.e. admission rate and duration) during the 12-months treatment period and 12-months following end of treatment |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1b. Monthly telephone interviews (Month 1-12) and end of study visit month 12 2b. At baseline and after 12 months 3b. At baseline and after 12 months 4b. At baseline and after 12 months 5b. At baseline and after 12 months 6b. Monthly telephone interviews (Month 1-12) and end of study visit month 12 |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | Yes |
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) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | Yes |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |