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Study in Japanese Pediatric Subjects With Short Bowel Syndrome (SBS) Who Are Dependent on Parenteral Support

Primary Purpose

Short Bowel Syndrome

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Teduglutide
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Short Bowel Syndrome

Eligibility Criteria

4 Months - 15 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Informed consent by a parent or guardian prior to any study-related procedures
  • When applicable, informed assent (as deemed appropriate by the Institutional Review Board) by the participant prior to any study-related procedures
  • Male or female infant 4 to <12 months corrected gestational age or child or adolescent aged 1 year through 15 years
  • Current history of SBS as a result of major intestinal resection (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis)
  • Short bowel syndrome that requires PN/IV support that provides at least 30% of caloric and/or fluid/electrolyte needs
  • Stable PN/IV support, defined as:

For infants 4 to <12 months corrected gestational age: Inability to significantly reduce PN/IV support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds) for at least 1 month prior to and during screening, as assessed by the investigator.

For children 1 to 15 years of age:

Inability to significantly reduce PN/IV support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds) for at least 3 months prior to and during screening, as assessed by the investigator.

Transient instability for events such as interruption of central access or treatment of sepsis is allowed if the PN/IV support returns to within 10% of baseline prior to the event.

- Sexually active female participants of childbearing potential must use medically acceptable methods of birth control during and for 4 weeks following the last dose of investigational product.

Exclusion Criteria:

  • Participants who are not expected to be able to advance oral or tube feeding regimens
  • Serial transverse enteroplasty or any other bowel lengthening procedure performed within 3 months of screening
  • Known clinically significant untreated intestinal obstruction contributing to feeding intolerance and inability to reduce parenteral support
  • Unstable absorption due to cystic fibrosis or other known DNA abnormalities (eg, Familial Adenomatous Polyposis, Fanconi-Bickel syndrome)
  • 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 parenteral support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding.
  • Evidence of clinically significant obstruction on the most recent upper GI series done within 6 months prior to screening.
  • Major GI surgical intervention including significant intestinal resection within 3 months prior to screening (insertion of feeding tube, anastomotic ulcer repair, minor intestinal resections <=10 centimeter (cm), or endoscopic procedure is allowed)
  • Unstable cardiac disease or congenital heart disease or cyanotic disease, with the exception of participants who had undergone ventricular or atrial septal defect repair, and patent ductus arteriosus (PDA) ligation
  • History of cancer or clinically significant lymphoproliferative disease, not including resected cutaneous basal or squamous cell carcinoma, or in situ nonaggressive and surgically resected cancer. Participants with known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of GI cancer (including hepatobiliary and pancreatic cancer) will also be excluded.
  • Pregnant or lactating female participants
  • Participation in a clinical study using an experimental drug (other than glutamine or Omegaven) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to screening and for the duration of the study
  • Previous use of teduglutide or native/synthetic GLP-2
  • Previous use of glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening
  • Previous use of octreotide or dipeptidyl peptidase-4 (DPP-4) inhibitors within 3 months prior to screening
  • Participants with active Crohn's disease who had been treated with biological therapy (eg, antitumor necrosis factor [anti-TNF]) within the 6 months prior to the screening visit
  • Participants with inflammatory bowel disease (IBD) who require chronic systemic immunosuppressant therapy that had been introduced or changed during the 3 months prior to screening
  • More than 3 serious complications of SBS (eg, documented infection-related catheter sepsis, clots, bowel obstruction, severe water-electrolyte disturbances) within 3 months prior to the screening visit
  • A serious complication that affects parenteral support requirements within 1 month prior to or during screening, excluding uncomplicated treatment of bacteremia, central line replacement/repair, or issues of similar magnitude in an otherwise stable participant
  • Body weight < 5 kilogram (kg) at screening and baseline visits
  • Signs of active, severe, or unstable clinically significant hepatic impairment during the screening period:

For infants 4 to <12 months corrected gestational age at least 2 of any of the following parameters:

  1. International normalized ratio (INR) >1.5 not corrected with parenteral vitamin K
  2. Platelet count <100×10^3/ (microliters)mcL due to portal hypertension
  3. Presence of clinically significant gastric or esophageal varices
  4. Documented cirrhosis
  5. Persistent cholestasis defined as conjugated bilirubin >4 milligram per deciliter (mg/dL) (>68 micromoles per liter [mcmol/L]) over a 2 week period

For children 1 to 15 years of age:

  1. Total bilirubin >= 2x upper limit of normal (ULN)
  2. Aspartate aminotransferase (AST) >= 7x ULN
  3. Alanine aminotransferase (ALT) >= 7x ULN

    • Signs of known continuous active or unstable, clinically significant renal dysfunction shown by results of an estimated glomerular filtration rate below 50 milliliter per minute (mL/min)/1.73 meter (m)^2
    • Parent(s)/guardian(s) and/or participants who are not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements
    • Unstable, clinically significant, active, untreated pancreatic or biliary disease
    • 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.

Sites / Locations

  • Kyushu University Hospital
  • Tsukuba University Hospital
  • Kagoshima University
  • Tohoku University Hospital
  • Showa University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Teduglutide

Arm Description

Participants will receive teduglutide 0.05 milligram per kilogram per day (mg/kg/day) subcutaneous (SC) injection once daily for 24 weeks.

Outcomes

Primary Outcome Measures

Absolute Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data
Absolute change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, milliliter per kilogram per day is abbreviated as mL/kg/day.
Percent Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data
Percent change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Absolute change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day).
Percent Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Percent change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From Baseline in Plasma Citrulline at End of Treatment (EOT)
Absolute change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From Baseline in Plasma Citrulline at End of Treatment (EOT)
Percent change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data
Absolute change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data
Percent change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Absolute change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Percent change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Number of Participants Who Achieved At Least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 24
Number of participants who achieved at least 20% reduction in PS volume at Week 24 was reported.
Number of Participants Who Achieved At Least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at End of Treatment (EOT)
Number of participants who achieved at least 20% reduction in PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning of Parenteral Support (PS) Volume at End of Treatment (EOT)
Number of participants who achieved at least 100% reduction in complete weaning of PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Number of Participants Who Achieved Greater Than or Equal to (>=) 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 28
Number of participants who achieved >= 20% reduction in PS volume at Week 28 was reported.
Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data
Absolute change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data
Percent change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data
Absolute change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data
Percent change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)
Absolute change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)
Percent change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data
Absolute change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data
Percent change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data
Absolute change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data
Percent change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From Baseline in Number of Hours Per Day of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data
Absolute change from baseline in number of hours per day of PS Usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data
Absolute change from baseline in number of days per Week of PS usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
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 any AEs whose onset occurred, severity worsened, or intensity increased after receiving the investigational product.
Change From Baseline in Body Weight for Age Z-score at Week 28
Body weight was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the 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 for age Z-score at Week 28 was reported.
Change From Baseline in Height for Age Z-score at Week 28
Height was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the 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 height for age Z-score at Week 28 was reported.
Change From Baseline in Head Circumference for Age Z-score at Week 28
Head circumference was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the 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 for age Z-score at Week 28 was reported.
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)
Vital sign assessments included pulse rate, blood pressure, or body temperature. Number of participants with clinically significant changes in vital signs by the investigator were recorded as TEAEs.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)
12-lead ECG was performed. Any change in ECG assessments which were deemed to be clinically significant changes were recorded as TEAEs.
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Clinical laboratory assessments included biochemistry, hematology, coagulation, urinalysis. The number of participants with clinically significant laboratory abnormalities were reported as TEAEs.
Change From Baseline in the Average Urine Output at Week 28
Average urine output was recorded in measured volume at Week 28 was recorded.
Change From Baseline in the Fecal Output at Week 28
Change from baseline in the fecal output (Average number of stools per day) at Week 28 was recorded.
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.
Number of Participants With Clinically Significant Abnormal Findings in Gastrointestinal (GI) Specific Testing
GI specific testing included colonoscopy or sigmoidoscopy, abdominal ultrasound, fecal occult blood testing, upper GI series with small bowel follow-through (UGI/SBFT). EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Number of participants with clinically significant abnormal findings in gastrointestinal specific testing were reported.
Area Under the Concentration-time Curve at Steady State (AUCtau,ss) of Teduglutide in Plasma
Since only 2 sparse pharmacokinetics (PK) samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Maximum Plasma Concentration at Steady-state (Cmax,ss) of Teduglutide in Plasma
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Minimum Plasma Concentration at Steady-state (Cmin.ss) of Teduglutide in Plasma
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Terminal-Phase Half-life (t1/2) of Teduglutide in Plasma
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Apparent Clearance (CL/F) of Teduglutide
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Apparent Volume of Distribution (V[Lambda z]/F) of Teduglutide
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.

Secondary Outcome Measures

Full Information

First Posted
November 30, 2016
Last Updated
February 1, 2022
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT02980666
Brief Title
Study in Japanese Pediatric Subjects With Short Bowel Syndrome (SBS) Who Are Dependent on Parenteral Support
Official Title
A 24-week Safety, Efficacy, Pharmacodynamic, and Pharmacokinetic Study of Teduglutide in Japanese Pediatric Subjects, Aged 4 Months Through 15 Years, With Short Bowel Syndrome Who Are Dependent on Parenteral Support
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
January 13, 2017 (Actual)
Primary Completion Date
January 21, 2020 (Actual)
Study Completion Date
January 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if an investigational treatment (teduglutide) is safe and effective in Japanese children (age 4 months through 15 years of age) with SBS who are dependent on parenteral support. This study will also evaluate how teduglutide moves through the body (pharmacokinetics) and how it affects the body (pharmacodynamics).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Short Bowel Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Teduglutide
Arm Type
Experimental
Arm Description
Participants will receive teduglutide 0.05 milligram per kilogram per day (mg/kg/day) subcutaneous (SC) injection once daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Teduglutide
Intervention Description
0.05 mg/kg/day SC injection once daily for 24 weeks.
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data
Description
Absolute change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, milliliter per kilogram per day is abbreviated as mL/kg/day.
Time Frame
Baseline, EOT (up to Week 24)
Title
Percent Change From Baseline in Parenteral Support (PS) Volume at End of Treatment (EOT) Based on Dairy Data
Description
Percent change from baseline in PS volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Absolute Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Description
Absolute change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Here, kilo-calories per kilogram per day was abbreviated as (kcal/kg/day).
Time Frame
Baseline, EOT (up to Week 24)
Title
Percent Change From Baseline in Parenteral Support (PS) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Description
Percent change from baseline in PS caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Absolute Change From Baseline in Plasma Citrulline at End of Treatment (EOT)
Description
Absolute change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Percent Change From Baseline in Plasma Citrulline at End of Treatment (EOT)
Description
Percent change from baseline in plasma citrulline at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Absolute Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data
Description
Absolute change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Percent Change From Baseline in Enteral Nutritional (EN) Volume at End of Treatment (EOT) Based on Dairy Data
Description
Percent change from baseline in EN volume at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Absolute Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Description
Absolute change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Percent Change From Baseline in Enteral Nutritional (EN) Caloric Intake at End of Treatment (EOT) Based on Dairy Data
Description
Percent change from baseline in EN caloric intake at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Number of Participants Who Achieved At Least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 24
Description
Number of participants who achieved at least 20% reduction in PS volume at Week 24 was reported.
Time Frame
Week 24
Title
Number of Participants Who Achieved At Least 20 Percent (%) Reduction in Parenteral Support (PS) Volume at End of Treatment (EOT)
Description
Number of participants who achieved at least 20% reduction in PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24)
Title
Number of Participants Who Achieved 100 Percent (%) Reduction in Complete Weaning of Parenteral Support (PS) Volume at End of Treatment (EOT)
Description
Number of participants who achieved at least 100% reduction in complete weaning of PS volume at EOT (up to Week 24) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24)
Title
Number of Participants Who Achieved Greater Than or Equal to (>=) 20 Percent (%) Reduction in Parenteral Support (PS) Volume at Week 28
Description
Number of participants who achieved >= 20% reduction in PS volume at Week 28 was reported.
Time Frame
Week 28
Title
Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data
Description
Absolute change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Volume at End of Study (EOS) Based on Dairy Data
Description
Percent change from EOT (up to Week 24) in PS volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Absolute Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data
Description
Absolute change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Percent Change From End of Treatment (EOT) in Parenteral Support (PS) Caloric Intake at End of Study (EOS) Based on Dairy Data
Description
Percent change from EOT (up to Week 24) in PS caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Absolute Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)
Description
Absolute change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Percent Change From End of Treatment (EOT) in Plasma Citrulline at End of Study (EOS)
Description
Percent change from EOT (up to Week 24) in plasma citrulline at EOS (up to Week 28) was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data
Description
Absolute change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Volume at End of Study (EOS) Based on Dairy Data
Description
Percent change from EOT (up to Week 24) in EN volume at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Absolute Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data
Description
Absolute change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Percent Change From End of Treatment (EOT) in Enteral Nutritional (EN) Caloric Intake at End of Study (EOS) Based on Dairy Data
Description
Percent change from EOT (up to Week 24) in EN caloric intake at EOS (up to Week 28) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
EOT (up to Week 24), EOS (up to Week 28)
Title
Absolute Change From Baseline in Number of Hours Per Day of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data
Description
Absolute change from baseline in number of hours per day of PS Usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment (EOT) Based on Dairy Data
Description
Absolute change from baseline in number of days per Week of PS usage at EOT (up to Week 24) based on dairy data was reported. EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period.
Time Frame
Baseline, EOT (up to Week 24)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description
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 any AEs whose onset occurred, severity worsened, or intensity increased after receiving the investigational product.
Time Frame
From start of study drug administration up to EOS (up to Week 28)
Title
Change From Baseline in Body Weight for Age Z-score at Week 28
Description
Body weight was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the 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 for age Z-score at Week 28 was reported.
Time Frame
Baseline, Week 28
Title
Change From Baseline in Height for Age Z-score at Week 28
Description
Height was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the 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 height for age Z-score at Week 28 was reported.
Time Frame
Baseline, Week 28
Title
Change From Baseline in Head Circumference for Age Z-score at Week 28
Description
Head circumference was measured using age Z-score. A Z-score was defined as the deviation of the value for an individual from the mean value of the reference population divided by the standard deviation for the 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 for age Z-score at Week 28 was reported.
Time Frame
Baseline, Week 28
Title
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)
Description
Vital sign assessments included pulse rate, blood pressure, or body temperature. Number of participants with clinically significant changes in vital signs by the investigator were recorded as TEAEs.
Time Frame
From start of study drug administration up to EOS (up to Week 28)
Title
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Treatment Emergent Adverse Events (TEAEs)
Description
12-lead ECG was performed. Any change in ECG assessments which were deemed to be clinically significant changes were recorded as TEAEs.
Time Frame
From start of study drug administration up to EOS (up to Week 28)
Title
Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Description
Clinical laboratory assessments included biochemistry, hematology, coagulation, urinalysis. The number of participants with clinically significant laboratory abnormalities were reported as TEAEs.
Time Frame
From start of study drug administration up to EOS (up to Week 28)
Title
Change From Baseline in the Average Urine Output at Week 28
Description
Average urine output was recorded in measured volume at Week 28 was recorded.
Time Frame
Baseline, Week 28
Title
Change From Baseline in the Fecal Output at Week 28
Description
Change from baseline in the fecal output (Average number of stools per day) at Week 28 was recorded.
Time Frame
Baseline, Week 28
Title
Number of Participants With Positive Specific Antibodies to Teduglutide
Description
Number of participants with positive specific antibodies to teduglutide were used to summarize the presence of antibodies.
Time Frame
From start of study drug administration up to EOS (up to Week 28)
Title
Number of Participants With Clinically Significant Abnormal Findings in Gastrointestinal (GI) Specific Testing
Description
GI specific testing included colonoscopy or sigmoidoscopy, abdominal ultrasound, fecal occult blood testing, upper GI series with small bowel follow-through (UGI/SBFT). EOT was defined as the last available measurement after the date of first dose during the 24-week treatment period. Number of participants with clinically significant abnormal findings in gastrointestinal specific testing were reported.
Time Frame
Baseline, EOT (up to Week 24)
Title
Area Under the Concentration-time Curve at Steady State (AUCtau,ss) of Teduglutide in Plasma
Description
Since only 2 sparse pharmacokinetics (PK) samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time Frame
Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
Title
Maximum Plasma Concentration at Steady-state (Cmax,ss) of Teduglutide in Plasma
Description
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time Frame
Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
Title
Minimum Plasma Concentration at Steady-state (Cmin.ss) of Teduglutide in Plasma
Description
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time Frame
Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
Title
Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma
Description
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time Frame
Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
Title
Terminal-Phase Half-life (t1/2) of Teduglutide in Plasma
Description
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time Frame
Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
Title
Apparent Clearance (CL/F) of Teduglutide
Description
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time Frame
Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose
Title
Apparent Volume of Distribution (V[Lambda z]/F) of Teduglutide
Description
Since only 2 sparse PK samples were collected during the study, PK parameters were not estimated and analyzed using this study samples. Therefore, no PK parameters were reported in this study.
Time Frame
Baseline: Pre-dose, 1, 6 hours post-dose; Week 4: Pre-dose, 2, 4 hours post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Months
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent by a parent or guardian prior to any study-related procedures When applicable, informed assent (as deemed appropriate by the Institutional Review Board) by the participant prior to any study-related procedures Male or female infant 4 to <12 months corrected gestational age or child or adolescent aged 1 year through 15 years Current history of SBS as a result of major intestinal resection (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis) Short bowel syndrome that requires PN/IV support that provides at least 30% of caloric and/or fluid/electrolyte needs Stable PN/IV support, defined as: For infants 4 to <12 months corrected gestational age: Inability to significantly reduce PN/IV support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds) for at least 1 month prior to and during screening, as assessed by the investigator. For children 1 to 15 years of age: Inability to significantly reduce PN/IV support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds) for at least 3 months prior to and during screening, as assessed by the investigator. Transient instability for events such as interruption of central access or treatment of sepsis is allowed if the PN/IV support returns to within 10% of baseline prior to the event. - Sexually active female participants of childbearing potential must use medically acceptable methods of birth control during and for 4 weeks following the last dose of investigational product. Exclusion Criteria: Participants who are not expected to be able to advance oral or tube feeding regimens Serial transverse enteroplasty or any other bowel lengthening procedure performed within 3 months of screening Known clinically significant untreated intestinal obstruction contributing to feeding intolerance and inability to reduce parenteral support Unstable absorption due to cystic fibrosis or other known DNA abnormalities (eg, Familial Adenomatous Polyposis, Fanconi-Bickel syndrome) 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 parenteral support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding. Evidence of clinically significant obstruction on the most recent upper GI series done within 6 months prior to screening. Major GI surgical intervention including significant intestinal resection within 3 months prior to screening (insertion of feeding tube, anastomotic ulcer repair, minor intestinal resections <=10 centimeter (cm), or endoscopic procedure is allowed) Unstable cardiac disease or congenital heart disease or cyanotic disease, with the exception of participants who had undergone ventricular or atrial septal defect repair, and patent ductus arteriosus (PDA) ligation History of cancer or clinically significant lymphoproliferative disease, not including resected cutaneous basal or squamous cell carcinoma, or in situ nonaggressive and surgically resected cancer. Participants with known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of GI cancer (including hepatobiliary and pancreatic cancer) will also be excluded. Pregnant or lactating female participants Participation in a clinical study using an experimental drug (other than glutamine or Omegaven) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to screening and for the duration of the study Previous use of teduglutide or native/synthetic GLP-2 Previous use of glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening Previous use of octreotide or dipeptidyl peptidase-4 (DPP-4) inhibitors within 3 months prior to screening Participants with active Crohn's disease who had been treated with biological therapy (eg, antitumor necrosis factor [anti-TNF]) within the 6 months prior to the screening visit Participants with inflammatory bowel disease (IBD) who require chronic systemic immunosuppressant therapy that had been introduced or changed during the 3 months prior to screening More than 3 serious complications of SBS (eg, documented infection-related catheter sepsis, clots, bowel obstruction, severe water-electrolyte disturbances) within 3 months prior to the screening visit A serious complication that affects parenteral support requirements within 1 month prior to or during screening, excluding uncomplicated treatment of bacteremia, central line replacement/repair, or issues of similar magnitude in an otherwise stable participant Body weight < 5 kilogram (kg) at screening and baseline visits Signs of active, severe, or unstable clinically significant hepatic impairment during the screening period: For infants 4 to <12 months corrected gestational age at least 2 of any of the following parameters: International normalized ratio (INR) >1.5 not corrected with parenteral vitamin K Platelet count <100×10^3/ (microliters)mcL due to portal hypertension Presence of clinically significant gastric or esophageal varices 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 For children 1 to 15 years of age: Total bilirubin >= 2x upper limit of normal (ULN) Aspartate aminotransferase (AST) >= 7x ULN Alanine aminotransferase (ALT) >= 7x ULN Signs of known continuous active or unstable, clinically significant renal dysfunction shown by results of an estimated glomerular filtration rate below 50 milliliter per minute (mL/min)/1.73 meter (m)^2 Parent(s)/guardian(s) and/or participants who are not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements Unstable, clinically significant, active, untreated pancreatic or biliary disease 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Shire
Official's Role
Study Director
Facility Information:
Facility Name
Kyushu University Hospital
City
Fukuoka-shi
State/Province
Fukuoka-ken
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Tsukuba University Hospital
City
Tsukuba
State/Province
Ibaraki-Ken
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Kagoshima University
City
Kagoshima-shi
State/Province
Kagoshima-Ken
ZIP/Postal Code
890-8520
Country
Japan
Facility Name
Tohoku University Hospital
City
Sendai-shi
State/Province
Miyagi-Ken
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Showa University
City
Shinagawa-ku
State/Province
Tokyo-To
ZIP/Postal Code
142-8555
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites, …).

Learn more about this trial

Study in Japanese Pediatric Subjects With Short Bowel Syndrome (SBS) Who Are Dependent on Parenteral Support

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