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

• ClinicalTrials.gov Identifier: NCT00081458
• Recruitment Status: Completed
• First Posted: April 14, 2004
• Results First Posted: July 15, 2013
• Last Update Posted: December 8, 2015
• Sponsor: Shire
• Information provided by (Responsible Party): Shire

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Short Bowel Syndrome	Drug: Placebo; Drug: Teduglutide 0.05 mg/kg/d; Drug: Teduglutide 0.1 mg/kg/d	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Study of the Efficacy and Safety of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome
• Study Start Date: April 2004
• Actual Primary Completion Date: July 2007
• Actual Study Completion Date: July 2007

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: placebo; Placebo injectable subcutaneously daily into the thigh or abdomen	Drug: Placebo; placebo injectable subcutaneously daily into thigh or abdomen
Experimental: 2; teduglutide 0.05 mg/kg/d	Drug: Teduglutide 0.05 mg/kg/d; Teduglutide 0.05 mg/kg/d daily injectable subcutaneously into the thigh or abdomen; Other Name: GATTEX
Experimental: 3; teduglutide 0.1 mg/kg/d	Drug: Teduglutide 0.1 mg/kg/d; Teduglutide 0.1 /g/kg/d daily injection subcutaneously into thigh or abdomen; Other Name: GATTEX

Outcome Measures

Primary Outcome Measures :

1. A Graded Response Score in Parenteral Nutrition (PN) Reduction [ Time Frame: 6 months ]

   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.

Secondary Outcome Measures :

1. Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24 [ Time Frame: 6 months of treatment ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

  Show 32 Study Locations

Sponsors and Collaborators

Shire

Investigators

• Study Director: Head Clinical Development; NPS

More Information

Additional Information:

Click here for accurate, up-to-date, and practical information for patients with Short Bowel Syndrome (SBS). 

Publications of Results:

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.

Other Publications:

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

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.

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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00081458 History of Changes
• Other Study ID Numbers: CL0600-004
• First Posted: April 14, 2004
• Results First Posted: July 15, 2013
• Last Update Posted: December 8, 2015
• Last Verified: September 2014

Keywords provided by Shire:

Short Bowel Syndrome; Parenteral Nutrition; SBS

Additional relevant MeSH terms:

Short Bowel Syndrome; Syndrome; Disease; Pathologic Processes; Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Teduglutide; Gastrointestinal Agents; Radiation-Protective Agents; Protective Agents; Physiological Effects of Drugs