Clinical trial NCT00081458: Safety and Efficacy Study of Teduglutide in Subjects With Short Bowel Syndrome
Official title: A Study of the Efficacy and Safety of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Keywords: Short Bowel Syndrome
Parenteral Nutrition
SBS
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2004-04-14
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of teduglutide compared with placebo in subjects with parenteral nutrition (PN)-dependent short bowel syndrome (SBS).

Detailed description: Teduglutide is an analog of glucagon-like peptide 2 (GLP-2), a naturally occurring hormone that regulates the growth, proliferation, and maintenance of cells lining the gastrointestinal tract. Teduglutide has been shown in animal studies and previous human clinical trials to increase the size and number of these cells, thereby increasing the absorptive surface area of the intestines.

The multicenter, double-blind, international Phase III trial will randomly assign approximately 80 patients to receive daily subcutaneous injections of 0.05 milligrams or 0.10 milligrams of teduglutide per kilogram of body weight, or a placebo. Dosing will continue for a period of six months. The primary endpoint in the study is a reduction in the use of intravenous feeding, which is often required to sustain life in patients with SBS.

Eligibility criteria: Inclusion Criteria:

* Men and women, aged 18 years of age or older at the time of signing the informed consent form (ICF)
* SBS as a result of major intestinal resection resulting in at least 12 months intravenous feeding
* Body weight must be less than 90 kg
* At baseline, subjects must require PN treatment to meet their caloric or electrolyte needs due to ongoing malabsorption at least 3 times weekly and to be on a stable PN regimen for 4 weeks before dosing
* Body mass index (BMI) 18 to 27 kg/m2
* Adequate hepatic and renal function

Exclusion Criteria:

* History of cancer or clinically significant lymphoproliferative disease with fewer than 5 years documented disease-free state
* History of alcohol or drug abuse (within previous year)
* Participation in a clinical study within 30 days prior to signing the ICF, or concurrent participation in any clinical study
* Clinically significant laboratory abnormalities at the time of randomization
* Previous use of teduglutide (ALX-0600)
* Prior use of native GLP-2 within 3 months of screening visit
* Hospital admission within 1 month prior to screening visit
* Pregnant or lactating women
* Any condition or circumstance, which in the investigator's opinion would put the subject at any undue risk, prevent completion of the study, or interfere with analysis of the study results.
* Presence of excluded disease: Radiation enteritis, Scleroderma, Celiac disease, Refractory/Tropical sprue, Pseudo-obstruction, Active inflammatory bowel disease (IBD), Pre-malignant/malignant change in colonoscopy biopsy or polypectomy, Surgery scheduled within the time frame of the study, Human immunodeficiency virus (HIV) positive test, Immunological disorders, Possible allergies to teduglutide or its constituents, Significant, active, uncontrolled, untreated systemic diseases

Primary outcomes:
measure: A Graded Response Score in Parenteral Nutrition (PN) Reduction
timeFrame: 6 months
Secondary outcomes:
measure: Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24
timeFrame: 6 months of treatment
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Center for Clinical Research
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania - Penn Nursing
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Brussels
country: Belgium
facility: l'Hôpital Erasme
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University of Copenhagen
city: Lille
country: France
facility: Hôpital Claude-Huriez
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Paris
country: France
facility: Hôpital Beaujon
city: Berlin
country: Germany
facility: Charité University Hospital
city: Berlin
country: Germany
facility: Charité-Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Olsztyn
country: Poland
facility: Pracownia Żywienia Klinicznego
city: Warsaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny-Im.prof W.Orłowskiego CMKP
city: Salford
country: United Kingdom
facility: Hope Hospital
state: Greater Manchester
city: Harrow
country: United Kingdom
facility: St. Mark's Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Dudrick SJ, Latifi R, Fosnocht DE. Management of the short-bowel syndrome. Surg Clin North Am. 1991 Jun;71(3):625-43. doi: 10.1016/s0039-6109(16)45438-1.
citation: Rombeau JL, Rolandelli RH. Enteral and parenteral nutrition in patients with enteric fistulas and short bowel syndrome. Surg Clin North Am. 1987 Jun;67(3):551-71. doi: 10.1016/s0039-6109(16)44232-5.
citation: Shanbhogue LK, Molenaar JC. Short bowel syndrome: metabolic and surgical management. Br J Surg. 1994 Apr;81(4):486-99. doi: 10.1002/bjs.1800810404.
citation: Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and adults. Gastroenterology. 1997 Nov;113(5):1767-78. doi: 10.1053/gast.1997.v113.pm9352883.
citation: Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011 Jul;60(7):902-14. doi: 10.1136/gut.2010.218271. Epub 2011 Feb 11.
citation: Fujioka K, Jeejeebhoy K, Pape UF, Li B, Youssef NN, Schneider SM. Patients With Short Bowel on Narcotics During 2 Randomized Trials Have Abdominal Complaints Independent of Teduglutide. JPEN J Parenter Enteral Nutr. 2017 Nov;41(8):1419-1422. doi: 10.1177/0148607116663481. Epub 2016 Aug 9.