Metabolic Balance Study of FE203799 in Patients With SBS With Intestinal Insufficiency

Study Overview
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Brief Summary
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This is a repeated dose, open label trial investigating safety, efficacy, PD and PK of FE 203799 in 8 patients with SBS. The patients will receive a subcutaneous (SC) dose of 5 mg FE 203799 once weekly for 4 consecutive weeks, and efficacy parameters and PK will be assessed after the fourth dose. Safety follow up assessments will be performed 4-6 weeks after the last dose.

Detailed Description
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This is a repeated dose, open label trial investigating safety, efficacy, PD and PK of FE 203799 in 8 patients with SBS . The patients will receive a subcutaneous (SC) dose of 5 mg FE 203799 once weekly for 4 consecutive weeks, and efficacy parameters and PK will be assessed after the fourth dose. Safety follow-up assessments will be performed 4-6 weeks after the last dose. The first two administrations of trial drug will be performed at the clinic, while the third dose can be either self-administered by the patient or administered at the clinic if the patient prefers to travel to the site or other considerations make a site visit preferable. The fourth administration of trial drug will be performed at the clinic just prior to assessment of efficacy parameters in the treatment balance study. Prior to each administration of trial drug, liver function parameters will be analysed and assessed. During the entire trial, patients who develop extremely high or persistently elevated liver enzymes following trial drug administration will be discontinued from the trial. The patients will complete a diary with data on trial drug administration performed at home, local tolerability and adverse events (AEs).

Official Title
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A Phase Ib/IIa Open-label, Repeated Dose, Metabolic Balance Study of FE 203799 in Patients With Short Bowel Syndrome and Intestinal Insufficiency

Conditions
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SBS - Short Bowel Syndrome

Intervention / Treatment
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* Drug: FE203799


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with SBS secondary to surgical resection of the small intestine, with or without an intact colon. 18-80 years of age Average faecal wet weight excretion of ≥1500 g/day during the baseline balance study Average urine production <2000 mL/day during the baseline balance study Body Mass Index (BMI) between 16.0 and 32.0 (both inclusive) At least 6 months since last surgical bowel resection 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) 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 and confirmed with follicle-stimulating hormone [FSH] test) Exclusion Criteria: Pregnancy or lactation Positive results on the human immunodeficiency virus (HIV), hepatitis B and/or C tests A history of clinically significant intestinal adhesions and/or chronic abdominal pain Require chronic systemic narcotics for treatment of pain that exceeds an amount corresponding to 80 mg of morphine per day History of cancer or clinically significant lymphoproliferative disease within ≤5 years, except for adequately treated basal cell skin cancer History of gallstone within the past 3 years. Gallstone with subsequent cholecystectomy to resolve the issues is acceptable. Inflammatory bowel disease patients (IBD) who have NOT been on a stable drug treatment regimen for at least the past 4 weeks Evidence of active IBD in the past 12 weeks Visible blood in the stool within the last 3 months 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 Radiation enteritis, scleroderma or other condition of intestinal dysmotility, coeliac disease, refractory or tropical sprue History of alcohol and/or drug abuse within the last 12 months 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 Inadequate renal function as defined by serum creatinine or blood urea nitrogen >2.5 x ULN Unplanned hospitalisation of >24 hours duration within 1 month before the screening visit Systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, infliximab, or other biologic therapy/immune modifiers within 30 days of screening Any use of growth hormone, glutamine or growth factors such as native GLP-2 or GLP-2 analogue within the last 3 months Any use of antibiotics within the last 30 days Participation in another clinical trial within the last 3 months and during this trial Previously been treated in this trial Loss of blood or donation of blood or plasma >500 mL within 3 months prior to screening Patient not capable of understanding or not willing to adhere to the trial visit schedules and other protocol requirements For any other reason judged not eligible by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FE203799 5 mg<br>FE203799 5 mg subcutaneous injection | Drug: FE203799<br>* FE203799 5 mg subcutaneous once weekly<br>* Other names: GLP 2 analogue;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Adverse events as assessed by CTCAE v4.03 | Day -28 to Day 26 plus 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of intestinal insufficiency and gut absorption | Changes in the wet weight (g) of faecal excretion | Day -28 to day 26 | 
| Assessment of intestinal insufficiency and gut absorption | Changes from baseline in lean body mass by DEXA scan. | Day -28 and day 26 | 
| Assessment of intestinal insufficiency and gut absorption | Changes from baseline in bone mineral content by DEXA scan. | Day -28 and day 26 | 
| Assessment of intestinal insufficiency and gut absorption | Changes from baseline in fat mass by DEXA scan. | Day -28 and day 26 | 
| Assessment of intestinal insufficiency and gut absorption | Measure of body weight (kg) | Day -28 to day 26 plus 6 weeks | 
| Assessment of intestinal insufficiency and gut absorption | Measurement of urinary output (ml) | Baseline (Day -6) to end of treatment (Day 26) | 
| Assessment of intestinal insufficiency and gut absorption | Measurement of urinary electrolytes (sodium, potassium, calcium, magnesium) (mmol/d) | Baseline (Day -6) to end of treatment (Day 26) | 
| Assessment of gut regeneration | Measurements of the plasma Citrulline (ng/ml) | Baseline (Day -7) to end of treatment period (Day 26) plus 6 weeks | 
| Maximum observed plasma concentration (Cmax) | Cmax (ng/ml) | Day 1 to end of treatment period (Day 26) | 
| Cumulative area under the plasma concentration (AUC) of FE 203799 from time 0 to 168 | AUC0-168 (ng*hr/ml) | Day 1 to end of treatment period (Day 26) | 
| Terminal elimination half-life (T1/2) of FE 203799 | T1/2 (h) | Day 1 to end of treatment period (Day 26) | 
| Apparent total body clearance (CL) of FE 203799 from plasma | CL (ml/hr) | Day 1 to end of treatment period (Day 26) | 
| Apparent volume of distribution (Vd) of FE 203799 during terminal phase | Vd (ml) | Day 1 to end of treatment period (Day 26) |