E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Short bowel syndrome (SBS) |
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E.1.1.1 | Medical condition in easily understood language |
Patients with SBS with intestinal failure have a reduced absorption in the intestines. Shortened intestines also lead to a changed hormone production. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049416 |
E.1.2 | Term | Short-bowel syndrome |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
To assess the safety and tolerability of FE 203799 in patients with SBS |
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E.2.2 | Secondary objectives of the trial |
•To assess the PD of FE 203799 in patients with SBS
•To assess the PK of FE 203799 in patients with SBS with
•To compare the PD and PK between SBS patients with intestinal insufficiency (SBS-II) and SBS patients with intestinal failure (SBS-IF)
•To evaluate markers indicative of a pharmacological effect of FE 203799
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Males and females with SBS-II secondary to surgical resection of the small intestine, with or without an intact colon
2.18-80 years of age
3.Average faecal wet weight excretion of ≥1500 g/day during the baseline balance study
4.Average urine production <2000 mL/day during the baseline balance study
5.Body Mass Index (BMI) between 16.0 and 32.0 (both inclusive)
6.At least 6 months since last surgical bowel resection
7.Willing to adhere to a defined oral intake of fluids on certain days as required by the protocol (and based on the individual’s routine daily consumption)
8.Women of childbearing potential must agree to use an adequate method of contraception during the trial and for 60 days after the end-of-trial visit. Adequate methods of contraception include intrauterine device or hormonal contraception (oral contraceptive pill, depot injections or implant, transdermal depot patch or vaginal ring). To be considered sterilised or infertile, females must have undergone surgical sterilisation (bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhoea may be confirmed with follicle-stimulating hormone [FSH] test if there is doubt)
9. Male subjects must commit to use barrier contraception (e.g. condom) during the trial and for 2-weeks after the end-of-trial visit |
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E.4 | Principal exclusion criteria |
1.Pregnancy or lactation
2.Positive results on the human immunodeficiency virus (HIV), hepatitis B and/or C tests
3.A history of clinically significant intestinal adhesions and/or chronic abdominal pain
4.Require chronic systemic narcotics for treatment of pain that exceeds an amount corresponding to 80 mg of morphine per day
5.History of cancer or clinically significant lymphoproliferative disease within ≤5 years, except for adequately treated basal cell skin cancer
6.History of gallstone within the past 3 years. Gallstone with subsequent cholecystectomy to resolve the issues is acceptable.
7.Inflammatory bowel disease patients (IBD) who have NOT been on a stable drug treatment regimen for at least the past 4 weeks
8.Evidence of active IBD in the past 12 weeks
9.Visible blood in the stool within the last 3 months
10.Decompensated heart failure (New York Heart Association [NYHA] class III-IV, see Appendix 12.2) and/or known coronary heart disease defined as unstable angina pectoris and/or myocardial infarction within the last 6 months prior to screening
11.Radiation enteritis, scleroderma or other condition of intestinal dysmotility, coeliac disease, refractory or tropical sprue
12.History of alcohol and/or drug abuse within the last 12 months
13.Inadequate hepatic function as defined by: bilirubin >upper limit of normal (ULN), alanine transaminase (ALT) or aspartate transaminase (AST) >2.0 × ULN; alkaline phosphatase (ALP) >2.5 × ULN; or international normalised ratio (INR) >1.5 × ULN
14.Inadequate renal function as defined by serum creatinine or blood urea nitrogen >2.5 x ULN
15.Unplanned hospitalisation of >24 hours duration within 1 month before the screening visit
16.Changes in systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, infliximab, or other biologic therapy/immune modifiers within 3 months of screening
17.Any use of growth hormone, glutamine or growth factors such as native GLP-2 or GLP-2 analogue within the last 3 months
18.Any use of antibiotics within the last 30 days
19.Participation in another clinical trial (except studies with catheter locks) within the last 3 months and during this trial
20.Previously been treated in this trial
21.Loss of blood or donation of blood or plasma >500 mL within 3 months prior to screening
22.Patient not capable of understanding or not willing to adhere to the trial visit schedules and other protocol requirements
23.For any other reason judged not eligible by the investigator
24. Catheter sepsis experienced within the last 3 months |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Adverse events (AEs; type, frequency and intensity), vital signs (systolic and diastolic blood pressure, heart rate), electrocardiogram (ECG; intervals, rhythm and morphology), clinical chemistry, haematology, haemostasis and urinalysis |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From screening visit to end of study, in total during approximately 14 weeks per patients.
An AE having onset after the first administration of trial drug is considered treatment emergent. |
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E.5.2 | Secondary end point(s) |
•Changes in faecal excretion of wet weight, energy, macronutrients (carbohydrate, nitrogen as a marker for protein and lipids) and electrolytes (sodium, potassium, calcium and magnesium) over 72 hours from baseline to end of treatment
•Changes in urine output and urinary electrolytes (sodium, potassium, calcium and magnesium) over 72 hours from baseline to end of treatment
•Changes in dietary intake of wet weight, energy, macronutrients (carbohydrate, nitrogen as a marker for protein and lipids) and electrolytes (sodium, potassium, calcium and magnesium) over 72 hours from baseline to end of treatment
•Changes in absolute and relative absorption of wet weight, energy, macronutrients (carbohydrate, nitrogen as a marker for protein and lipids) and electrolytes (sodium, potassium, calcium and magnesium) over 72 hours from baseline to end of treatment
•Change in body weight from baseline to end of treatment
•Changes from baseline in lean body mass, bone mineral content and fat mass by dual-energy X-ray absorptiometry (DEXA) scan from baseline to end of treatment
•Change in plasma citrulline level from baseline to end of treatment
•FE 203799 PK parameters: Cmax, Tmax, AUCτ, AUCτ/dose, λZ, terminal T½, CL/F, V/F, Fluctuation index
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary efficacy endpoints are all concerned with the change from baseline to the end of treatment for the following parameters: |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Metabolic balance, changes in urine output, citrulline blood analyse, and local tolerability. |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |