A Phase Ib/IIa Open-label, Repeated Dose, Metabolic Balance Study of FE 203799 in Patients With Short Bowel Syndrome and Intestinal Insufficiency
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
FE203799 5 mg
FE203799 5 mg subcutaneous injection
干预措施: FE203799 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: Day -28 to Day 26 plus 6 weeks
Adverse events as assessed by CTCAE v4.03
次要结局
- Assessment of gut regeneration(Baseline (Day -7) to end of treatment period (Day 26) plus 6 weeks)
- Cumulative area under the plasma concentration (AUC) of FE 203799 from time 0 to 168(Day 1 to end of treatment period (Day 26))
- Terminal elimination half-life (T1/2) of FE 203799(Day 1 to end of treatment period (Day 26))
- Apparent total body clearance (CL) of FE 203799 from plasma(Day 1 to end of treatment period (Day 26))
- Apparent volume of distribution (Vd) of FE 203799 during terminal phase(Day 1 to end of treatment period (Day 26))
- Assessment of intestinal insufficiency and gut absorption(Baseline (Day -6) to end of treatment (Day 26))
- Maximum observed plasma concentration (Cmax)(Day 1 to end of treatment period (Day 26))