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

Phase 3

Completed

• Conditions: Short Bowel Syndrome
• Interventions: Drug: teduglutide 0.05 mg/kg/d; Drug: teduglutide 0.10 mg/kg/d

• Registration Number: NCT00172185
• Lead Sponsor: Shire

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2005-01-10
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-15
• Primary Completion: 2008-01-24
• Study Completion: 2008-01-24
• Results First Submitted: 2013-03-12
• Results First Submitted QC: 2013-03-12
• Results First Posted: 2013-04-23
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-12
• Last Update Posted: 2021-06-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
teduglutide 0.05 mg/kg/d	teduglutide 0.05 mg/kg/d	0.05 mg/kg/d teduglutide subcutaneous injection
teduglutide 0.10 mg/kg/d	teduglutide 0.10 mg/kg/d	0.10 mg/kg/d teduglutide subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Number of Subjects Achieving a 20% Reduction at Week 28	28 weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (21)

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Hôpital Erasme; 🇧🇪 Brussels, Belgium

St. Mark's Hospital; 🇬🇧 Harrow, United Kingdom

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Hôpital Lariboisière; 🇫🇷 Paris, France

Academic Medical Center, Department of Endocrinology & Metabolism; 🇳🇱 Amsterdam, Netherlands

Pracownia Żywienia; 🇵🇱 Olsztyn, Poland

Samodzielny Publiczny Szpital Kliniczny-Im.prof W.Orłowskiego CMKP; 🇵🇱 Warsaw, Poland

St. Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Albany Medical Center; 🇺🇸 Albany, New York, United States

Mayo Clinic Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

University of Pennsylvania - Penn Nursing; 🇺🇸 Philadelphia, Pennsylvania, United States

Hôpital de la Croix-Rousse; 🇫🇷 Lyon, France

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Hôpital Huriez; 🇫🇷 Lille, France

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States