Short Bowel Syndrome
Conditions
Brief summary
The objectives of this clinical study are to evaluate the safety, efficacy, and pharmacokinetics (PK) of teduglutide in Japanese participants with short bowel syndrome (SBS) who are dependent on parenteral nutrition/intravenous (PN/IV) over a 24-week treatment period.
Interventions
DRUGTeduglutide
Teduglutide 0.05 mg/kg SC injection will be administered once daily into 1 of the 4 quadrants of the abdomen or either thigh or arm.
DEVICESyringe
Teduglutide will be administered using syringe. Syringe is approved for use in Japan by Pharmaceuticals and Medical Devices Agency (PMDA).
DEVICENeedle
Teduglutide will be administered using needle. Needle is approved for use in Japan by PMDA.
DEVICEVial Adapter for Device
Vial adapter for device is approved for use in Japan by PMDA.
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to voluntarily provide written, signed, and informed consent to participate in the study. 2. Male or female 16 years of age or older at the time of signing informed consent. 3. Intestinal failure due to short bowel syndrome (SBS) as a result of major intestinal resection (example, due to injury, volvulus, vascular disease, cancer, Crohn's disease) that resulted in at least 12 continuous months of parenteral nutrition/intravenous (PN/IV) dependence at the time of informed consent. 4. Parenteral nutrition requirement of at least 3 times per week during the week before the screening visit and during the 2 weeks prior to the baseline visit. 5. Stable PN/IV requirement for at least 4 consecutive weeks immediately prior to the start of teduglutide treatment. Stability is defined as: a. Actual PN/IV usage is similar to prescribed PN/IV; b. Baseline (Visit 2) 48-hour oral fluid intake and urine output (I/O) volumes fall within +/- 25 percent (%) of the respective 48-hour I/O volumes at the last optimization visit; c. Urine output volume should NOT fall below 2 liter (L) and should not exceed 4 L per 48 hours at the last optimization visit, the stabilization visit, and the baseline visit. 6. For participants with a history of Crohn's disease, clinical remission for at least 12 weeks prior to the baseline visit as demonstrated by clinical assessment, which may include procedure-based evidence of remission. 7. Females of childbearing potential must agree to comply with the contraceptive requirements of the protocol. 8. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Exclusion criteria
1. Participation in a clinical study using an experimental drug within 30 days or 5.5 halflives, whichever is longer, prior to screening, or concurrent participation in any other clinical study. 2. Use of glucagon-like peptide (GLP)-2 or human growth hormone or analogs of these hormones within the past 6 months. 3. Use of octreotide, GLP-1 analogs, dipeptidyl peptidase-IV inhibitors, or enteral glutamine within 30 days. 4. Previous use of teduglutide. 5. Participants with active inflammatory bowel disease (IBD) or participants with IBD who received a change in immunosuppressant therapy (example, azathioprine, anti- tumor necrosis factor (TNFs)) within the past 6 months. 6. Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, familial adenomatous polyposis, etc. 7. Chronic intestinal pseudo-obstruction or severe dysmotility. 8. Clinically significant intestinal stenosis or obstruction, or evidence of such on upper gastrointestinal (GI) series with small bowel follow-through, within the past 6 months. 9. Major GI surgical intervention, including bowel lengthening procedures, within the past 3 months (insertion of feeding tube or endoscopic procedure is allowed). 10. Unstable cardiac disease, (example, congestive heart failure, cyanotic disease, or congenital heart disease). 11. Moderate or severe renal impairment, defined as creatinine clearance less than (\<) 50 millilitre (ml)/ minute (min). 12. Currently diagnosed with cancer or a history of any cancer except surgically curative skin cancer within the past 5 years. 13. Severe hepatobiliary disease including: a. Total bilirubin level greater than or equal to (\>=) 2 times the upper limit of normal (ULN); b. Aspartate aminotransferase (AST) \>=5 times ULN; c. Alanine aminotransferase (ALT) \>=5 times ULN. 14. Active clinically significant pancreatic disease, including clinical signs of pancreatitis associated with elevations in serum amylase or lipase \>=2 times ULN. 15. More than 4 SBS-related or PN/IV-related hospital admissions (example, central line associated bloodstream infection, bowel obstruction, severe fluid/electrolyte disturbances) within the past 12 months. 16. Unscheduled hospitalization within 30 days prior to screening. 17. Pregnant or lactating female. 18. Any condition or circumstance that in the investigator's opinion put the participant at any undue risk, prevent completion of the study, or interfere with analysis of the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hematocrit at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in hematocrit at EOT/ET was reported. |
| Change From Baseline in Creatinine at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in creatinine at EOT/ET was reported. |
| Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in weekly PS volume at EOT/ET was reported. |
| Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Percent change from baseline in weekly PS volume at EOT/ET was reported. |
| Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 20 | Baseline, Week 20 | Percentage of participants who achieved at least 20% reduction from baseline in weekly PS volume at Week 20 was reported. |
| Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 24 | Baseline, Week 24 | Percentage of participants who achieved at least 20% reduction from baseline in weekly PS volume at Week 24 was reported. |
| Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Percentage of participants who achieve at least 20% reduction from baseline in weekly PS at EOT/ET was reported. |
| Change From Baseline in Days Per Week of Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in days per week of PS at EOT/ET was reported. |
| Change From Baseline in Plasma Citrulline Levels at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Plasma citrulline levels were measured as a biomarker of enterocyte mass. Change from baseline in plasma citrulline levels up to EOT/ET was reported. |
| Number of Participants Who Were Completely Weaned Off Parenteral Support (PS) at Week 24/End of Treatment (EOT) | Week 24/EOT | Number of participants who were completely weaned off PS at Week 24/EOT was reported. |
| Area Under the Plasma Concentration-Time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Teduglutide | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | AUC0-t of teduglutide was reported. |
| Maximum Plasma Concentration (Cmax) of Teduglutide | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | Cmax of teduglutide was reported. |
| Change From Baseline in Serum Blood Urea Nitrogen (BUN) at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in serum blood urea nitrogen at EOT/ET was reported. |
| Time to Maximum Plasma Concentration (Tmax) of Teduglutide | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | Tmax of teduglutide was reported. |
| Terminal-phase Half-life (T1/2) of Teduglutide | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | T1/2 of teduglutide was reported. |
| Apparent Clearance (CL/F) of Teduglutide | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | CL/F of teduglutide was reported. |
| Apparent Volume of Distribution (Vz/F) of Teduglutide | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | Vz/F of teduglutide was reported. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From start of study drug administration up to EOT/ET (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 were defined as AEs whose onset occurred, severity worsened, or intensity increased after receiving the study medication. |
| Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) | From start of study drug administration up to EOT/ET (up to Week 28) | 12-lead ECG was performed at the study center after the participant has been resting for at least 5 minutes. Number of participants with clinically significant abnormalities in 12-Lead ECG was reported. |
| Change From Baseline in Blood Pressure at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in systolic and diastolic blood pressure at EOT/ET was reported. |
| Change From Baseline in Pulse Rate at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in pulse rate at EOT/ET was reported. |
| Change From Baseline in Body Temperature at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in body temperature at EOT/ET was reported. |
| Change From Baseline in Hemoglobin at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in hemoglobin at EOT/ET was reported. |
| Change From Baseline in Urine Sodium at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in urine sodium at EOT/ET was reported. |
| Number of Participants Who Reported Positive Specific Antibodies to Teduglutide at End of Treatment/Early Termination (EOT/ET) | EOT/ET (up to Week 28) | Number of participants who reported positive specific antibodies to teduglutide at EOT/ET was reported. |
| Change From Baseline in 48-Hour Urine Output at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in 48-hour urine output at EOT/ET was reported. |
| Change From Baseline in Body Weight at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in body weight at EOT/ET was reported. |
| Change From Baseline in Body Mass Index (BMI) at End of Treatment/Early Termination (EOT/ET) | Baseline, EOT/ET (up to Week 28) | Change from baseline in BMI at EOT/ET was reported. |
| Number of Participants With Abnormal Clinically Significant Changes in Gastrointestinal (GI) Specific Tests at Week 24/ET (Early Termination) | Week 24/ET | GI specific tests included colonoscopy or sigmoidoscopy, abdominal ultrasound, upper GI series with small bowel follow-through (UGI/SBFT). Number of participants with abnormal clinically significant changes in gastrointestinal specific tests at Week 24/ET was reported. |
Countries
Japan
Participant flow
Recruitment details
The study was conducted at 5 sites in Japan between 06 July 2018 (first participant first visit) and 06 August 2019 (last participant last visit).
Pre-assignment details
A total of 7 participants were enrolled and received the treatment. Out of them, 6 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Teduglutide Participants received 0.05 milligram per kilogram (mg/kg) of teduglutide subcutaneous (SC) injection once daily into 1 of the 4 quadrants of the abdomen or either thigh or arm for 24 weeks. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Teduglutide |
|---|---|
| Age, Continuous | 40.4 years STANDARD_DEVIATION 8.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 3 / 7 |
Outcome results
Primary
Apparent Clearance (CL/F) of Teduglutide
CL/F of teduglutide was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12
Population: PK population included all participants who received at least 1 dose of teduglutide and had at least 1 evaluable post-dose pharmacokinetic concentration value. Here, the number of participants analyzed refer to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Apparent Clearance (CL/F) of Teduglutide | 10858.9 Milliliter per hour (mL/h) | Standard Deviation 4038.5 |
Primary
Apparent Volume of Distribution (Vz/F) of Teduglutide
Vz/F of teduglutide was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12
Population: PK population included all participants who received at least 1 dose of teduglutide and had at least 1 evaluable post-dose pharmacokinetic concentration value. Here, the number of participants analyzed refer to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Apparent Volume of Distribution (Vz/F) of Teduglutide | 17167.4 Milliliter (mL) | Standard Deviation 8371.9 |
Primary
Area Under the Plasma Concentration-Time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Teduglutide
AUC0-t of teduglutide was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12
Population: Pharmacokinetic (PK) population included all participants who received at least 1 dose of teduglutide and had at least 1 evaluable post-dose pharmacokinetic concentration value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Area Under the Plasma Concentration-Time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Teduglutide | 240.3 Hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 80.651 |
Primary
Change From Baseline in 48-Hour Urine Output at End of Treatment/Early Termination (EOT/ET)
Change from baseline in 48-hour urine output at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in 48-Hour Urine Output at End of Treatment/Early Termination (EOT/ET) | 213.57 Milliliter per day (mL/day) | Standard Deviation 242.757 |
Primary
Change From Baseline in Blood Pressure at End of Treatment/Early Termination (EOT/ET)
Change from baseline in systolic and diastolic blood pressure at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teduglutide | Change From Baseline in Blood Pressure at End of Treatment/Early Termination (EOT/ET) | Systolic Blood Pressure: EOT (up to Week 28) | 2.4 Millimetre of mercury (mmHg) | Standard Deviation 19.37 |
| Teduglutide | Change From Baseline in Blood Pressure at End of Treatment/Early Termination (EOT/ET) | Diastolic Blood Pressure: EOT (up to Week 28) | 6.6 Millimetre of mercury (mmHg) | Standard Deviation 20.59 |
Primary
Change From Baseline in Body Mass Index (BMI) at End of Treatment/Early Termination (EOT/ET)
Change from baseline in BMI at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Body Mass Index (BMI) at End of Treatment/Early Termination (EOT/ET) | 0.07 Kilograms per square meter (kg/m^2) | Standard Deviation 0.441 |
Primary
Change From Baseline in Body Temperature at End of Treatment/Early Termination (EOT/ET)
Change from baseline in body temperature at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Body Temperature at End of Treatment/Early Termination (EOT/ET) | -0.03 Degree Celsius | Standard Deviation 0.411 |
Primary
Change From Baseline in Body Weight at End of Treatment/Early Termination (EOT/ET)
Change from baseline in body weight at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Body Weight at End of Treatment/Early Termination (EOT/ET) | 0.164 kilogram (kg) | Standard Deviation 1.1146 |
Primary
Change From Baseline in Creatinine at End of Treatment/Early Termination (EOT/ET)
Change from baseline in creatinine at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Creatinine at End of Treatment/Early Termination (EOT/ET) | -5.6 Micromoles per liter (mcmol/L) | Standard Deviation 8.42 |
Primary
Change From Baseline in Days Per Week of Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET)
Change from baseline in days per week of PS at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Days Per Week of Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET) | -0.43 Days per Week | Standard Deviation 1.134 |
Primary
Change From Baseline in Hematocrit at End of Treatment/Early Termination (EOT/ET)
Change from baseline in hematocrit at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Hematocrit at End of Treatment/Early Termination (EOT/ET) | -0.014 Volume per volume (v/v) | Standard Deviation 0.0355 |
Primary
Change From Baseline in Hemoglobin at End of Treatment/Early Termination (EOT/ET)
Change from baseline in hemoglobin at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Hemoglobin at End of Treatment/Early Termination (EOT/ET) | -3.9 Gram per liter (g/L) | Standard Deviation 12.94 |
Primary
Change From Baseline in Plasma Citrulline Levels at End of Treatment/Early Termination (EOT/ET)
Plasma citrulline levels were measured as a biomarker of enterocyte mass. Change from baseline in plasma citrulline levels up to EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Plasma Citrulline Levels at End of Treatment/Early Termination (EOT/ET) | 11.973 Micromoles (mcmol) | Standard Deviation 11.7309 |
Primary
Change From Baseline in Pulse Rate at End of Treatment/Early Termination (EOT/ET)
Change from baseline in pulse rate at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Pulse Rate at End of Treatment/Early Termination (EOT/ET) | 2.6 Beats per minute (beats/min) | Standard Deviation 9.88 |
Primary
Change From Baseline in Serum Blood Urea Nitrogen (BUN) at End of Treatment/Early Termination (EOT/ET)
Change from baseline in serum blood urea nitrogen at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Serum Blood Urea Nitrogen (BUN) at End of Treatment/Early Termination (EOT/ET) | 0 mmol/L | Standard Deviation 0 |
Primary
Change From Baseline in Urine Sodium at End of Treatment/Early Termination (EOT/ET)
Change from baseline in urine sodium at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Urine Sodium at End of Treatment/Early Termination (EOT/ET) | -2.1 millimoles per liter (mmol/L) | Standard Deviation 64.92 |
Primary
Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
Change from baseline in weekly PS volume at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | -2.92 Liter per week (L/Week) | Standard Deviation 3.463 |
Primary
Maximum Plasma Concentration (Cmax) of Teduglutide
Cmax of teduglutide was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12
Population: PK population included all participants who received at least 1 dose of teduglutide and had at least 1 evaluable post-dose pharmacokinetic concentration value.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Maximum Plasma Concentration (Cmax) of Teduglutide | 49.50 Nanograms per milliliter (ng/mL) | Standard Deviation 16.427 |
Primary
Number of Participants Who Reported Positive Specific Antibodies to Teduglutide at End of Treatment/Early Termination (EOT/ET)
Number of participants who reported positive specific antibodies to teduglutide at EOT/ET was reported.
Time frame: EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide | Number of Participants Who Reported Positive Specific Antibodies to Teduglutide at End of Treatment/Early Termination (EOT/ET) | 1 Participants |
Primary
Number of Participants Who Were Completely Weaned Off Parenteral Support (PS) at Week 24/End of Treatment (EOT)
Number of participants who were completely weaned off PS at Week 24/EOT was reported.
Time frame: Week 24/EOT
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Teduglutide | Number of Participants Who Were Completely Weaned Off Parenteral Support (PS) at Week 24/End of Treatment (EOT) | Weaned Off Parenteral Support: No | 7 Participants |
| Teduglutide | Number of Participants Who Were Completely Weaned Off Parenteral Support (PS) at Week 24/End of Treatment (EOT) | Weaned Off Parenteral Support: Yes | 0 Participants |
Primary
Number of Participants With Abnormal Clinically Significant Changes in Gastrointestinal (GI) Specific Tests at Week 24/ET (Early Termination)
GI specific tests included colonoscopy or sigmoidoscopy, abdominal ultrasound, upper GI series with small bowel follow-through (UGI/SBFT). Number of participants with abnormal clinically significant changes in gastrointestinal specific tests at Week 24/ET was reported.
Time frame: Week 24/ET
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide | Number of Participants With Abnormal Clinically Significant Changes in Gastrointestinal (GI) Specific Tests at Week 24/ET (Early Termination) | 0 Participants |
Primary
Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG)
12-lead ECG was performed at the study center after the participant has been resting for at least 5 minutes. Number of participants with clinically significant abnormalities in 12-Lead ECG was reported.
Time frame: From start of study drug administration up to EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide | Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) | 0 Participants |
Primary
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 were defined as AEs whose onset occurred, severity worsened, or intensity increased after receiving the study medication.
Time frame: From start of study drug administration up to EOT/ET (up to Week 28)
Population: Safety population included all participants in the ITT population who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teduglutide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 7 Participants |
Primary
Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET)
Percentage of participants who achieve at least 20% reduction from baseline in weekly PS at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teduglutide | Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET) | 57.1 Percentage of participants |
Primary
Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 20
Percentage of participants who achieved at least 20% reduction from baseline in weekly PS volume at Week 20 was reported.
Time frame: Baseline, Week 20
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit. Here, number of participants analyzed refer to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teduglutide | Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 20 | 66.7 Percentage of participants |
Primary
Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
Percentage of participants who achieved at least 20% reduction from baseline in weekly PS volume at Week 24 was reported.
Time frame: Baseline, Week 24
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit. Here, number of participants analyzed refer to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teduglutide | Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 24 | 66.7 Percentage of participants |
Primary
Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
Percent change from baseline in weekly PS volume at EOT/ET was reported.
Time frame: Baseline, EOT/ET (up to Week 28)
Population: ITT population included all participants who were deemed eligible for teduglutide treatment at the baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teduglutide | Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | -22.19 Percent change | Standard Deviation 24.953 |
Primary
Terminal-phase Half-life (T1/2) of Teduglutide
T1/2 of teduglutide was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12
Population: PK population included all participants who received at least 1 dose of teduglutide and had at least 1 evaluable post-dose pharmacokinetic concentration value. Here, the number of participants analyzed refer to the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teduglutide | Terminal-phase Half-life (T1/2) of Teduglutide | 1.09 Hour |
Primary
Time to Maximum Plasma Concentration (Tmax) of Teduglutide
Tmax of teduglutide was reported.
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12
Population: PK population included all participants who received at least 1 dose of teduglutide and had at least 1 evaluable post-dose pharmacokinetic concentration value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Teduglutide | Time to Maximum Plasma Concentration (Tmax) of Teduglutide | 3.00 Hour |