Safety and Efficacy Study of Teduglutide in Subjects With Short Bowel Syndrome Who Completed Protocol CL0600-004 (NCT00081458)

Study Overview
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Brief Summary
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The purpose of this clinical study is to evaluate the long-term safety and efficacy of daily administration of teduglutide.

Detailed Description
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Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2), a peptide secreted by L-cells of the distal intestine. GLP-2 is known to increase intestinal and portal blood flow, and inhibit gastric acid secretion. Teduglutide binds to the glucagon-like peptide-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF). This multicenter, double-blind, international, Phase III trial will have a treatment period of 28 weeks. Subjects in this study are those who received teduglutide or placebo in protocol CL0600-004 (NCT00081458). These subjects will receive daily subcutaneous injections of 0.05 milligrams or 0.10 milligrams of teduglutide per kilogram of body weight. Subjects will have visits every 4 to 6 weeks and will be assessed for parenteral nutrition (PN) reduction with a follow-up period of 4 weeks duration for those subjects who do not complete this protocol, or do not enter into the long-term safety extension protocol CL0600-010.

Official Title
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A Study of the Safety and Efficacy of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome Who Completed Protocol CL0600-004 (NCT00081458)

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: teduglutide 0.05 mg/kg/d
* Drug: teduglutide 0.10 mg/kg/d


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At dosing week 24 of protocol CL0600-004 (NCT00081458), subjects will be reviewed for their participation in this study. Subjects who meet all of the following criteria can be enrolled in this study: Signed and dated informed consent form (ICF) to participate before any study-related procedures are performed Completion of protocol CL0600-004 (NCT00081458) 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) Prior use of native glucagon-like peptide 2 (GLP-2) within 3 months of 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: teduglutide 0.05 mg/kg/d<br>0.05 mg/kg/d teduglutide subcutaneous injection | Drug: teduglutide 0.05 mg/kg/d<br>* 0.05 mg/kg/d subcutaneous injection<br>* Other names: GATTEX;|
| Experimental: teduglutide 0.10 mg/kg/d<br>0.10 mg/kg/d teduglutide subcutaneous injection | Drug: teduglutide 0.10 mg/kg/d<br>* 0.10 mg/kg/d subcutaneous injection<br>* Other names: GATTEX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving a 20% Reduction at Week 28 | For those subjects who received teduglutide (0.05 or 0.10 mg dose) in Study 004 and the same in Study 005, Parenteral Nutrition (PN) Use at Week 28 was compared to the Baseline Visit of Study 004 to calculate the 20% reduction in PN Use. For those subjects who received placebo in Study 004 and either teduglutide 0.05 or 0.10 mg dose in Study 005, PN Use at Week 28 was compared to the use of PN at Week 24 of Study 004 to calculate the 20% reduction in PN Use. | 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use (Responder Status is Yes or No) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short Bowel Syndrome, Parenteral Nutrition, SBS, Teduglutide