Short Bowel Syndrome
Conditions
Keywords
Short Bowel Syndrome, Parenteral Nutrition, SBS, Teduglutide
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.
Interventions
0.05 mg/kg/d subcutaneous injection
DRUGteduglutide 0.10 mg/kg/d
0.10 mg/kg/d subcutaneous injection
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
Belgium, Canada, Denmark, France, Netherlands, Poland, United Kingdom, United States
Participant flow
Recruitment details
10Jan2005 - First Subject Enrolled 24Jan2008 - Last Subject Completed
Pre-assignment details
This was a 28-week study of the safety and efficacy of teduglutide in subjects with parenteral nutrition-dependent short bowel syndrome who completed protocol CL0600-004
Participants by arm
| Arm | Count |
|---|---|
| Placebo/0.05 Received placebo in Study 004/ Received Teduglutide 0.05 mg/kg/d in Study 005 | 6 |
| Placebo/0.10 Received placebo in Study 004/ Received Teduglutide 0.10 mg/kg/d in Study 005 | 7 |
| 0.05/0.05 Received Teduglutide 0.05 mg/kg/d in Study 004/ Received Teduglutide 0.05 mg/kg/d in Study 005 | 25 |
| 0.10/0.10 Received Teduglutide 0.10 mg/kg/d in Study 004/ Received Teduglutide 0.10 mg/kg/d in Study 005 | 27 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 3 | 4 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
| Overall Study | SPONSOR Decision | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo/0.05 | Placebo/0.10 | 0.05/0.05 | 0.10/0.10 |
|---|---|---|---|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 13.61 | 42.2 years STANDARD_DEVIATION 14.06 | 56.6 years STANDARD_DEVIATION 9.74 | 46.7 years STANDARD_DEVIATION 13.48 | 49.4 years STANDARD_DEVIATION 14.04 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 5 Participants | 7 Participants | 22 Participants | 25 Participants |
| Sex: Female, Male Female | 32 Participants | 4 Participants | 4 Participants | 10 Participants | 14 Participants |
| Sex: Female, Male Male | 33 Participants | 2 Participants | 3 Participants | 15 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 7 / 7 | 22 / 25 | 26 / 27 |
| serious Total, serious adverse events | 2 / 6 | 3 / 7 | 13 / 25 | 9 / 27 |
Outcome results
Primary
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.
Time frame: 28 weeks
Population: Number of participants for analysis was determined based on completing all of the prerequisite visits in Study 005. Subjects who dropped out of the study were considered failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/0.05 | Number of Subjects Achieving a 20% Reduction at Week 28 | 5 Participants |
| Placebo/0.10 | Number of Subjects Achieving a 20% Reduction at Week 28 | 3 Participants |
| 0.05/0.05 | Number of Subjects Achieving a 20% Reduction at Week 28 | 17 Participants |
| 0.10/0.10 | Number of Subjects Achieving a 20% Reduction at Week 28 | 14 Participants |
Secondary
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)
Time frame: 6 months
Population: Response Status is Yes or No
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/0.05 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: Yes | 4 participants |
| Placebo/0.05 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: No | 2 participants |
| Placebo/0.10 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: No | 5 participants |
| Placebo/0.10 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: Yes | 2 participants |
| 0.05/0.05 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: Yes | 17 participants |
| 0.05/0.05 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: No | 8 participants |
| 0.10/0.10 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: Yes | 10 participants |
| 0.10/0.10 | Number of Subjects Who Achieved at Least a One-Day Reduction in Parenteral Nutrition (PN) Use | Response Status: No | 17 participants |