Short Bowel Syndrome
Conditions
Keywords
SBS, short bowel syndrome, TPN, parenteral nutrition, PN
Brief summary
Teduglutide is an investigative medicine being evaluated as a possible treatment for people with parenteral nutrition (PN) dependent Short Bowel Syndrome (SBS). Teduglutide is similar to a protein the body makes. When people have SBS, their bodies do not make enough of the protein and they have trouble getting nutrients and fluids from the food they eat and drink. This study was designed to provide evidence of efficacy, safety, and tolerability of teduglutide 0.05 mg/kg daily in SBS subjects.
Interventions
DRUGteduglutide
0.05 mg/kg/day sc injection for 24 weeks
DRUGplacebo
Matching daily subcutaneous dose of placebo to teduglutide for 24 weeks
Sponsors
Nycomed
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent prior to any study-related procedures are performed * Men and women 18 years of age or older at the time of informed consent signing * Intestinal failure resulting in Short Bowel Syndrome * At least 12 months of continuous PN dependency * 12 weeks of clinical remission of Crohn's disease (CD) prior to dosing * PN required at least 3 times weekly * A stable PN volume for four weeks prior to dosing
Exclusion criteria
* History of cancer or clinically significant lymphoproliferative disease with fewer than 5 years documented disease-free state * Participation in clinical study within 30 days for drug or 90 days for antibody * Use of native GLP-2 or human growth hormone (HGH) within 6 months of screening * Use of iv glutamine within 30 days prior to screening * Use of teduglutide * CD patients who have been treated with biological therapy within 6 months of screening * IBD patients who require chronic systemic immunosuppressant therapy * More than 4 SBS- or PN-related hospitalizations within 12 months of screening * Unplanned hospitalization within one month of screening * Pregnant or lactating women * Body weight \> 88kg * Body mass index (BMI) \< 15 kg/m2 * Severe hepatic impairment or disturbed renal function * Female subjects who are not surgically sterile or postmenopausal or who are not using medically acceptable methods of birth control during and for 30 days after the treatment period * Not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements * Any condition or circumstance that is the investigator's opinion would put the subject at any undue risk, prevent completion of the study, or interfere with the analysis of the study results * Significant active, uncontrolled, untreated systemic diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder | Weeks 20 and 24 | Comparison of subjects treated with teduglutide to placebo who achieve a 20 to 100% reduction from baseline in weekly parenteral nutrition/intravenous fluid (PN/I.V.) volume at weeks 20 and 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in PN/I.V. Volume From Baseline to Last Time Point | Week 0 to last visit when data was collected. | Absolute change in the volume of PN/I.V. from baseline (Week 0) to the visit when the last data point was collected (week 4 through week 24, or earlier if the subject discontinued early). |
Countries
Canada, Denmark, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
First Patient Screened - November 25, 2008; Last Patient Screened - July 13, 2010; First Patient Randomized - March 3, 2009; Last Patient Randomized - July 22, 2010; Locations - hospitals and transplant centers; Subjects must be on parenteral nutrition (PN) and/or intravenous (I.V.) fluids.
Pre-assignment details
Stage 1 was screening, optimization, and stabilization periods. At screening, if the PN/I.V. volume is not stable per protocol, s/he entered an optimization period (up to 8 weeks) to find the minimally tolerated stable volume of PN/I.V.. Prior to randomization, all entered 4-8 weeks of stabilization period on that volume of PN/I.V.
Participants by arm
| Arm | Count |
|---|---|
| Teduglutide 0.05 mg/kg/day subcutaneous (sc) dose of teduglutide | 43 |
| Placebo Matching sc dose of placebo to teduglutide | 43 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Randomized in error by site | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Teduglutide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50.9 years STANDARD_DEVIATION 12.6 | 49.7 years STANDARD_DEVIATION 15.6 | 50.3 years STANDARD_DEVIATION 14.1 |
| Sex: Female, Male Female | 22 Participants | 24 Participants | 46 Participants |
| Sex: Female, Male Male | 21 Participants | 19 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 42 | 34 / 43 |
| serious Total, serious adverse events | 15 / 42 | 12 / 43 |
Outcome results
Primary
Responder
Comparison of subjects treated with teduglutide to placebo who achieve a 20 to 100% reduction from baseline in weekly parenteral nutrition/intravenous fluid (PN/I.V.) volume at weeks 20 and 24.
Time frame: Weeks 20 and 24
Population: Percentages were based on the number of subjects in the Intent to Treat (ITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teduglutide | Responder | 27 subjects |
| Placebo | Responder | 13 subjects |
p-value: 0.002Cochran-Mantel-Haenszel
Secondary
Absolute Change in PN/I.V. Volume From Baseline to Last Time Point
Absolute change in the volume of PN/I.V. from baseline (Week 0) to the visit when the last data point was collected (week 4 through week 24, or earlier if the subject discontinued early).
Time frame: Week 0 to last visit when data was collected.
Population: Intent-to-Treat (ITT) was defined for efficacy analyses which included all randomized patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Absolute Change in PN/I.V. Volume From Baseline to Last Time Point | -4.28 Liters/Week | Standard Deviation 3.81 |
| Placebo | Absolute Change in PN/I.V. Volume From Baseline to Last Time Point | -2.38 Liters/Week | Standard Deviation 2.79 |
Comparison: Last Dosing Visitp-value: <0.001ANCOVA