Short Bowel Syndrome
Conditions
Keywords
Short bowel syndrome, Teduglutide
Brief summary
The purpose of the study is to evaluate the safety, efficacy/pharmacodynamics (PD) and pharmacokinetics (PK) of teduglutide treatment in infants with short bowel syndrome (SBS) dependent on parenteral (PN) support.
Interventions
DRUGTeduglutide
SC injection of 0.05 mg/kg teduglutide will be administered QD into abdomen or into either the thigh or arm for 24 weeks.
OTHERStandard Medical Therapy
Standard medical therapy will be administered for 24 weeks.
DEVICESyringe
Teduglutide will be administered using syringe (510k number: K980987).
DEVICENeedle
Teduglutide will be administered using needle (510k number: K021475).
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Months to 12 Months
Healthy volunteers
No
Inclusion criteria
* Informed consent by the parent or legal guardian. * Male or female infant 4 to 12 months corrected gestational age at screening. * Weight at least 5 kilogram (kg) and weight-for-length Z-score greater than -2 at screening and baseline. * Short bowel syndrome with dependence on parenteral support to provide at least 50% of fluid or caloric needs. * Stable PN requirements for at least 1 month prior to screening, defined as a less than or equal to (\<=) 10% change in the weight-normalized PN total fluid and caloric intake, despite attempts to wean PN, not withstanding transient instability for events such as sepsis or interruption of central venous access. * Parent or legal guardian understands and is willing and able to fully adhere to study requirements as defined in this protocol.
Exclusion criteria
* Previous treatment with teduglutide. * Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, etc. * Severe, known dysmotility syndrome, such as pseudo-obstruction or persistent, severe, active gastroschisis-related dysmotility, that is the primary contributing factor to feeding intolerance and inability to reduce PN support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding. * Inability to advance oral or enteral feeding due to lack of access to the gut, such as oral aversion in the absence of a feeding tube. * Intestinal obstruction or clinically significant intestinal stenosis. * Major gastrointestinal surgical intervention, such as serial transverse enteroplasty or major intestinal resection or anastomosis, within 3 months prior to screening or planned during the study period. * Unstable cardiac disease. * Renal dysfunction, defined as estimated glomerular filtration rate less than (\<) 50 milliliter per minute (mL/min) per 1.73 square meter (m\^2). * Biliary obstruction, stenosis, or malformation. * Clinically significant pancreatic disease. * Severe hepatic dysfunction or portal hypertension, defined by at least 2 of the following parameters: 1. International normalized ratio (INR) greater than (\>) 1.5 not corrected with PN vitamin K 2. Platelet count \<100×10\^3/ microliter (mcL) due to portal hypertension 3. Presence of clinically significant gastric or esophageal varices 4. Documented cirrhosis * Persistent cholestasis defined as conjugated bilirubin \>4 milligram per deciliter (mg/dL) (\>68 micromoles per liter \[mcmol/L\]) over a 2 week period. * More than 3 serious complications of intestinal failure (example \[e.g.\], catheter-associated bloodstream infections, interruption of nutrition due to feeding intolerance, catheter-associated thrombosis, severe fluid or electrolyte disturbances) within 1 month prior to or during screening. * A history of cancer or a known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of gastrointestinal cancer (including hepatobiliary and pancreatic cancers). * Concurrent treatment with glucagon-like peptide-1 (GLP-1); glucagon-like peptide-2 (GLP-2); insulin-like growth factor-1 (IGF-1); growth hormone, somatostatin, or analogs of these hormones; or glutamine. * Participation in a clinical study using an experimental drug within 3 months or 5.5 half-lives of the experimental drug, whichever is longer. * Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients. * Any condition, disease, illness, or circumstance that, in the investigator's opinion, puts the participant at any undue risk, prevents completion of the study, or interferes with analysis of the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Number of participants who achieved at least 20% reduction from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From start of study treatment up to end of study (EOS) (up to Week 28) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs that start or deteriorate on or after the date of the first dose of investigational product. |
| Change From Baseline in Body Weight Z-score at Week 24 | Baseline, Week 24 | Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in body weight Z-score at Week 24 was reported. |
| Change From Baseline in Length Z-Score at Week 24 | Baseline, Week 24 | Length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in length Z-score at Week 24 was reported. |
| Change From Baseline in Head Circumference Z-Score at Week 24 | Baseline, Week 24 | Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in head circumference Z-score at Week 24 was reported. |
| Change From Baseline in Weight-for-Length Z-Score at Week 24 | Baseline, Week 24 | Weight-for-length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in weight-for-length Z-score at Week 24 was reported. |
| Change From Baseline in Average Total Urine Output at Week 24 | Baseline, Week 24 | Average total urine output was recorded over a 48-hour period of nutritional stability at Week 24 was reported. Here, milliliter per kilogram per day is abbreviated as mL/kg/day. |
| Change From Baseline in Fecal Output at Week 24 | Baseline, Week 24 | Change from baseline in the fecal output (average number of stools per day) at Week 24 was reported. |
| Number of Participants With Positive Specific Antibodies to Teduglutide | Baseline, EOS (up to week 28) | Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies. |
| Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Number of participants who achieved at least 20% reduction from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24 | Week 24 | Number of participants who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at Week 24 were reported. |
| Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7) | Baseline: Pre-dose,1, 4 hours post-dose, and 2 hours post-dose at Week 7 | Mean plasma concentration of teduglutide was reported. |
| Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Percent change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day). |
| Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Percent change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Percent change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Percent change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Number of participants who achieved at least 20% increase from baseline in weight-normalized EN volume at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 24) | Number of participants who achieved at least 20% increase from baseline in weight-normalized EN caloric intake at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. |
| Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS) | EOS (up to Week 28) | Number of participants who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at EOS (up to Week 28) were reported. |
Countries
Finland, France, Italy, United Kingdom
Participant flow
Recruitment details
The study was conducted at Finland and United Kingdom between 31 August 2018 (first participant first visit) and 24 September 2020 (last participant last visit).
Pre-assignment details
A total of 10 participants were enrolled into the study, of which 8 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Teduglutide (TED) Participants (infants) 4 to 12 months of corrected gestational aged received 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injection QD in addition to standard medical therapy for 24 weeks. | 5 |
| Standard of Care (SOC) Participants (infants) 4 to 12 months of corrected gestational aged received standard medical therapy for 24 weeks. | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Severe diarrhea | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Standard of Care (SOC) | Total | Teduglutide (TED) |
|---|---|---|---|
| Age, Continuous | 8.3 Months STANDARD_DEVIATION 2.65 | 8.4 Months STANDARD_DEVIATION 2.71 | 8.5 Months STANDARD_DEVIATION 3.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 5 / 5 | 5 / 5 |
| serious Total, serious adverse events | 4 / 5 | 3 / 5 |
Outcome results
Primary
Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
Number of participants who achieved at least 20% reduction from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: Intent-to-Treat (ITT) set consisted of all participants randomized in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 3 Participants |
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 3 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 1 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 3 Participants |
Secondary
Change From Baseline in Average Total Urine Output at Week 24
Average total urine output was recorded over a 48-hour period of nutritional stability at Week 24 was reported. Here, milliliter per kilogram per day is abbreviated as mL/kg/day.
Time frame: Baseline, Week 24
Population: Safety set consisted of all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Average Total Urine Output at Week 24 | -0.61 mL/kg/day | Standard Deviation 14.548 |
| Standard of Care (SOC) | Change From Baseline in Average Total Urine Output at Week 24 | 10.25 mL/kg/day | Standard Deviation 17.383 |
Secondary
Change From Baseline in Body Weight Z-score at Week 24
Body weight was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in body weight Z-score at Week 24 was reported.
Time frame: Baseline, Week 24
Population: Safety set consisted of all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Body Weight Z-score at Week 24 | -0.408 Z-score | Standard Deviation 0.377 |
| Standard of Care (SOC) | Change From Baseline in Body Weight Z-score at Week 24 | -0.289 Z-score | Standard Deviation 0.278 |
Secondary
Change From Baseline in Fecal Output at Week 24
Change from baseline in the fecal output (average number of stools per day) at Week 24 was reported.
Time frame: Baseline, Week 24
Population: Safety set consisted of all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Fecal Output at Week 24 | -3.33 Average number of stools per day | Standard Deviation 3.547 |
| Standard of Care (SOC) | Change From Baseline in Fecal Output at Week 24 | 1.67 Average number of stools per day | Standard Deviation 1.756 |
Secondary
Change From Baseline in Head Circumference Z-Score at Week 24
Head circumference was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in head circumference Z-score at Week 24 was reported.
Time frame: Baseline, Week 24
Population: Safety set consisted of all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Head Circumference Z-Score at Week 24 | -0.544 Z-Score | Standard Deviation 0.446 |
| Standard of Care (SOC) | Change From Baseline in Head Circumference Z-Score at Week 24 | -0.167 Z-Score | Standard Deviation 0.69 |
Secondary
Change From Baseline in Length Z-Score at Week 24
Length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in length Z-score at Week 24 was reported.
Time frame: Baseline, Week 24
Population: Safety set consisted of all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Length Z-Score at Week 24 | -0.274 Z-Score | Standard Deviation 1.258 |
| Standard of Care (SOC) | Change From Baseline in Length Z-Score at Week 24 | -0.422 Z-Score | Standard Deviation 0.384 |
Secondary
Change From Baseline in Weight-for-Length Z-Score at Week 24
Weight-for-length was measured using Z-score. Z-score was calculated as (observed value - median value of the reference population)/standard deviation value of reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean. Change from baseline in weight-for-length Z-score at Week 24 was reported.
Time frame: Baseline, Week 24
Population: Safety set consisted of all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Weight-for-Length Z-Score at Week 24 | -0.447 Z-Score | Standard Deviation 1.042 |
| Standard of Care (SOC) | Change From Baseline in Weight-for-Length Z-Score at Week 24 | -0.058 Z-Score | Standard Deviation 0.992 |
Secondary
Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
Change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 9.08 kcal/kg/day | Standard Deviation 10.662 |
| Teduglutide (TED) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -1.15 kcal/kg/day | Standard Deviation 2.306 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -9.38 kcal/kg/day | Standard Deviation 21.402 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 3.11 kcal/kg/day | Standard Deviation 16.285 |
Secondary
Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET)
Change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 16.14 mL/kg/day | Standard Deviation 18.683 |
| Teduglutide (TED) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -1.28 mL/kg/day | Standard Deviation 2.563 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -15.25 mL/kg/day | Standard Deviation 31.496 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 2.27 mL/kg/day | Standard Deviation 22.232 |
Secondary
Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
Change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day).
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number analyzed signifies participants who were evaluable for this outcome at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -16.14 kcal/kg/day | Standard Deviation 17.547 |
| Teduglutide (TED) | Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -15.31 kcal/kg/day | Standard Deviation 17.839 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -6.10 kcal/kg/day | Standard Deviation 10.386 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -20.40 kcal/kg/day | Standard Deviation 21.024 |
Secondary
Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
Change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number analyzed signifies participants who were evaluable for this outcome at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -21.54 mL/kg/day | Standard Deviation 28.909 |
| Teduglutide (TED) | Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -22.90 mL/kg/day | Standard Deviation 26.94 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -9.51 mL/kg/day | Standard Deviation 7.497 |
| Standard of Care (SOC) | Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -14.90 mL/kg/day | Standard Deviation 12.323 |
Secondary
Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS)
Number of participants who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at EOS (up to Week 28) were reported.
Time frame: EOS (up to Week 28)
Population: ITT set consisted of all participants randomized in the study. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide (TED) | Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS) | 0 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at End of Study (EOS) | 0 Participants |
Secondary
Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24
Number of participants who achieved 100% reduction in complete weaning off (enteral autonomy) PS volume at Week 24 were reported.
Time frame: Week 24
Population: ITT set consisted of all participants randomized in the study. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide (TED) | Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24 | 0 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning Off (Enteral Autonomy) Parenteral Support (PS) Volume at Week 24 | 0 Participants |
Secondary
Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
Number of participants who achieved at least 20% increase from baseline in weight-normalized EN caloric intake at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 2 Participants |
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 0 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 0 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 2 Participants |
Secondary
Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET)
Number of participants who achieved at least 20% increase from baseline in weight-normalized EN volume at EOT/ET was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 2 Participants |
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 0 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 0 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Increase From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 2 Participants |
Secondary
Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
Number of participants who achieved at least 20% reduction from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 3 Participants |
| Teduglutide (TED) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 3 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 1 Participants |
| Standard of Care (SOC) | Number of Participants Who Achieved At Least 20 Percent (%) Reduction From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 3 Participants |
Secondary
Number of Participants With Positive Specific Antibodies to Teduglutide
Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies.
Time frame: Baseline, EOS (up to week 28)
Population: Safety set: all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Data for this outcome was not planned to be collected and analyzed for SOC group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide (TED) | Number of Participants With Positive Specific Antibodies to Teduglutide | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs that start or deteriorate on or after the date of the first dose of investigational product.
Time frame: From start of study treatment up to end of study (EOS) (up to Week 28)
Population: Safety set consisted of all participants who met the following criteria: Teduglutide treatment arm: participants who received at least 1 dose of teduglutide and had undergone at least 1 post baseline safety assessment; Standard of care treatment arm: participants who had undergone at least 1 post baseline safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide (TED) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Standard of Care (SOC) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
Secondary
Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
Percent change from baseline in weight-normalized EN caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 207.06 Percent change | Standard Deviation 153.159 |
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -16.40 Percent change | — |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -44.25 Percent change | Standard Deviation 78.847 |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 24.18 Percent change | Standard Deviation 78.115 |
Secondary
Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET)
Percent change from baseline in weight-normalized EN volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | 273.20 Percent change | Standard Deviation 246.784 |
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -16.40 Percent change | — |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -44.25 Percent change | Standard Deviation 78.847 |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Enteral Nutrition (EN) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | 14.80 Percent change | Standard Deviation 69.834 |
Secondary
Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET)
Percent change from baseline in weight-normalized PS caloric intake at EOT/ET (up to Week 24) were reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number analyzed signifies participants who were evaluable for this outcome at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -27.00 Percent change | Standard Deviation 29.473 |
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -27.81 Percent change | Standard Deviation 30.777 |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -13.68 Percent change | Standard Deviation 21.873 |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Caloric Intake at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -38.86 Percent change | Standard Deviation 39.893 |
Secondary
Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
Percent change from baseline in weight-normalized PS volume at EOT/ET (up to Week 24) was reported. EOT/ET was defined as the last available visit after the date of first dose (or randomization in standard of care treatment group) during the 24-week treatment period.
Time frame: Baseline, EOT/ET (up to Week 24)
Population: ITT set consisted of all participants randomized in the study. Here, the number analyzed signifies participants who were evaluable for this outcome at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -24.77 Percent change | Standard Deviation 34.723 |
| Teduglutide (TED) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -27.28 Percent change | Standard Deviation 33.518 |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Diary Data: EOT/ET | -16.75 Percent change | Standard Deviation 16.392 |
| Standard of Care (SOC) | Percent Change From Baseline in Weight-normalized Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Prescribed Data: EOT/ET | -22.39 Percent change | Standard Deviation 17.198 |
Secondary
Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7)
Mean plasma concentration of teduglutide was reported.
Time frame: Baseline: Pre-dose,1, 4 hours post-dose, and 2 hours post-dose at Week 7
Population: Pharmacokinetic (PK) set consisted of all participants who received at least 1 dose of teduglutide and had at least 1 evaluable and interpretable post-dose PK concentration value. Here, the number of participants analyzed signifies participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specific time point. Data was not planned to be collected and analyzed for SOC arm.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Teduglutide (TED) | Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7) | Baseline: At Pre-dose | 0.00 Nanogram per milliliter (ng/mL) |
| Teduglutide (TED) | Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7) | Baseline: At 1 hour | 16.300 Nanogram per milliliter (ng/mL) |
| Teduglutide (TED) | Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7) | Baseline: At 4 hours | 8.385 Nanogram per milliliter (ng/mL) |
| Teduglutide (TED) | Plasma Concentration of Teduglutide at Nominal Time Points (Baseline at Pre-dose, and 1 Hour and 4 Hours Post-dose; 2 Hours Post-dose at Week 7) | Week 7: At 2 hours | 16.950 Nanogram per milliliter (ng/mL) |