Safety and Efficacy Study of Teduglutide in Subjects With Short Bowel Syndrome

Short Bowel Syndrome Clinical Trial

Official title:

A Study of the Efficacy and Safety of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00081458
• Other study ID #: CL0600-004
• Secondary ID: 2004-000438-35
• Status: Completed
• Phase: Phase 3
• Start date: May 25, 2004
• Est. completion date: July 6, 2007

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: July 6, 2007
• Est. primary completion date: July 6, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• Placebo
placebo injectable subcutaneously daily into thigh or abdomen
• Teduglutide 0.05 mg/kg/d
Teduglutide 0.05 mg/kg/d daily injectable subcutaneously into the thigh or abdomen
• Teduglutide 0.1 mg/kg/d
Teduglutide 0.1 /g/kg/d daily injection subcutaneously into thigh or abdomen

Locations

Country	Name	City	State
Belgium	l'Hôpital Erasme	Brussels
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Denmark	Rigshospitalet, University of Copenhagen	Copenhagen
France	Hôpital Claude-Huriez	Lille
France	Hôpital de la Croix-Rousse	Lyon
France	Hôpital Edouard Herriot	Lyon
France	Hôpital Beaujon	Paris
Germany	Charité University Hospital	Berlin
Germany	Charité-Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Frankfurt	Frankfurt
Netherlands	Academic Medical Center	Amsterdam
Poland	Pracownia Zywienia Klinicznego	Olsztyn
Poland	Samodzielny Publiczny Szpital Kliniczny-Im.prof W.Orlowskiego CMKP	Warsaw
United Kingdom	St. Mark's Hospital	Harrow
United Kingdom	Hope Hospital	Salford	Greater Manchester
United States	Albany Medical Center	Albany	New York
United States	Emory University Hospital	Atlanta	Georgia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Center for Clinical Research	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Mount Sinai School of Medicine	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania - Penn Nursing	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  France,  Germany,  Netherlands,  Poland,  United Kingdom, 

References & Publications (5)

Dudrick SJ, Latifi R, Fosnocht DE. Management of the short-bowel syndrome. Surg Clin North Am. 1991 Jun;71(3):625-43. Review. — View 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):90 — View 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. — View Citation

Shanbhogue LK, Molenaar JC. Short bowel syndrome: metabolic and surgical management. Br J Surg. 1994 Apr;81(4):486-99. Review. — View Citation

Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and adults. Gastroenterology. 1997 Nov;113(5):1767-78. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	A Graded Response Score in Parenteral Nutrition (PN) Reduction	The intensity of the response relied on a reduction from Baseline in weekly parenteral nutrition (PN) volume (minimum reduction of 20% and a maximum of 100%). Duration of the response incorporated responses at Weeks(Wk) 16-20 and at Wk20-24. Zero (0 - lowest) assigned if <20% reduction at Wk20-24 and reduction at Wk16-20 of < 20%, 20-39%, or >=40%. One (1) assigned if reduction of 20-39% at Wk20-24 but < 20% at Wk16-20. Two(2) assigned if reductions of 40-99% at Wk20-24 AND <20% at Wk16-20 OR 20-39% at Wk20-24 AND 20-39% at Wk16-20. Three (3) assigned if reductions of 100% at Wk20-24 AND <20% at Wk16-20 OR 40-99% at Wk20-24 AND 20-39% at Wk16-20 OR 20-39% at Wk20-24 AND >=40% at Wk16-20. Four (4) assigned if reductions of 100% at Wk20-24 AND 20-39% at Wk16-20 OR 40-99% at Wk20-24 AND >=40% at Wk16-20.	6 months
Secondary	Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24	An efficacy responder was defined as achieving at least a 20% reduction from Baseline to Week 20 and maintained at Week 24 in weekly actual PN infusion volume.	6 months of treatment