Clinical Trials

Inclusion Criteria:

• Signed informed consent for this trial prior to any trial specific assessment.
• Male and female subjects with SBS-IF, receiving PS, secondary to surgical resection of the small intestine with < 200 cm from duodeno-jejunal flexure, based on available medical/surgical records and with either:
  • CIC remaining and neither jejunostomy nor ileostomy with the latest intestinal resection being at least 12 months prior to screenin ; OR
  • Jejunostomy or ileostomy with the latest intestinal resection being at least 6 months prior to screening.
• Subject is considered optimized (average drinking volume is ≥ 1.0 L and ≤ 3.5 L per day and the average urinary volume is ≥ 0.8 L and ≤ 2.5 L per day) at trial Visit 2a, 2b, or 2c 4. Subject is considered stable with regard to PS volume requirement, drinking volume and urinary output at last stability visit and Visit 4*.
• Parenteral support requirement of at least 3 days per week as assessed before Screening and at the time of randomization.
• Willingness to adhere to an individual pre-defined drinking menu and urine measurements during the 48-hour fluid balance periods.
• No planned restorative surgery, or major intestinal surgery (more than 10% intestinal resection or surgery that changes anatomy group; i.e., stoma or CIC), in the trial period.
• Age ≥ 18 years at Screening.
• Women of childbearing potential must agree to practice effective contraception and to use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit. Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner. To be considered sterilized or infertile, females must have undergone surgical sterilization (bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be post-menopausal (defined as at least 12 months amenorrhea without an alternative medical cause; may be confirmed with follicle-stimulating hormone test if there is doubt). Women who do not engage in heterosexual intercourse will be allowed to join the trial without contraception following a thorough discussion with the Investigator to determine if this is feasible for the subject. The following methods are not considered acceptable methods of contraception: calendar, ovulation, symptothermal, post-ovulation methods, withdrawal (coitus interruptus), spermicides only, and the lactational amenorrhea method.
• Male subjects with a female partner of childbearing potential must commit to practice methods of contraception (e.g., condom, vasectomy) and abstain from sperm donation during the trial and for 2 weeks after the EOT visit. Nevertheless, their partners, if they are women of childbearing potential, must agree to practice contraception and to use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit. Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device; intrauterine hormone-releasing system.
• Willingness to undergo either a colonoscopy or colonography (if anatomically feasible) and have any identified polyps removed.

* Actual PS usage matches prescribed PS (± 10% deviation), urine volume of last optimization and last stability testing visit match (± 25% deviation) while the drinking volume is constant (differ by max 10% and is ≥ 1.0 L and ≤ 3.5 L per day) and urine volume on average is ≥ 0.8 L and ≤ 2.5 L per day.

Exclusion Criteria:

• Pregnancy and/or lactation.
• Major abdominal surgery (more than 10% intestinal resection or surgery that changes anatomy group) in the last 6 months prior to Screening Visit. Surgery for feeding tube placement and cholecystectomy allowed.
• A history of clinically significant intestinal adhesions increasing the risk of GI obstruction and/or GI contrast study(s) of remaining small bowel suggesting subacute intestinal obstruction or mild stricture within 6 months prior to Screening.
• Constipation which is not adequately managed by dietary recommendations, laxatives or cathartic medications.
• Active or untreated enterocutaneous fistula.
• History of cancer (including colon carcinoma) or clinically significant lymphoproliferative disease within ≤ 5 years, except for adequately treated basal cell skin cancer.
• Acute cholecystitis or biliary obstruction untreated in the 1 month prior to or during the screening period.
• Subjects with active inflammatory bowel diseases (IBD) or underlying condition who require new drug treatment or regimen changes, including increased or decreased dose of a previously administered treatment, within the previous 3 months prior to randomization.
• Central venous catheter sepsis experienced within the previous 2 months prior to and during screening or a catheter infection requiring the use of systemic antibiotics within 30 days prior to Screening.
• Decompensated heart failure (New York Heart Association [NYHA] class III-IV) and/or known coronary heart disease defined as unstable angina pectoris and/or myocardial infarction within the previous 6 months prior to Screening.
• Radiation enteritis, scleroderma or residual evidence of intestinal dysmotility, including pseudo-obstruction and Hirschsprung’s disease, coeliac disease, refractory or tropical sprue.
• History of alcohol and/or drug abuse within the previous 12 months prior to Screening.
• Child-Pugh scale Class C.
• Evidence of chronic renal disease as demonstrated by inadequate renal function, which is defined as estimated glomerular filtration rate (eGFR) 500 mL within 3 months prior to the Screening Visit. 
• Positive results for human immunodeficiency virus (HIV), hepatitis A, B and/or C tests at the Screening Visit 4.
• Elevated liver enzymes during the screening period:
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN);
  • Alanine aminotransferase or AST > 3 x ULN and total bilirubin > 2 x ULN or international normalized ratio (INR) > 1.5 for a person not using anticoagulant drug and INR > 3 for a person on anticoagulant therapy such as warfarin;
  • Alanine aminotransferase or AST > 3 x ULN and clinical signs of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia;
  • Subjects with serum conjugated bilirubin > 34 μmol/L during two consecutive measurements;
  • Dubject not capable of understanding or not willing to adhere to the trial visit schedules and/or other protocol requirements;
  • Judged not eligible by the Investigator for any other reason;
  • Subject has been diagnosed with any variant of familial adenomatous polyposis.

** Subjects recovered from hepatitis B or C can be enrolled; i.e., they have markers of the infection, but the viral load is undetectable. Subjects with evidence of an acute or chronically active hepatitis B or C infection should be excluded. If a subject has a positive HAV IgM, this would indicate an acute infection and the subject is ineligible. but he/she may be eligible for re-screening after recovery.

Eligibility last updated 4/18/22. Questions regarding updates should be directed to the study team contact.