Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Teduglutide in Japanese Subjects With PN-dependent Short Bowel Syndrome (SBS)

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02340819
• Collaborator: (none)
• Enrollment: 11
• Locations: 5
• Arm: 1
• Actual Duration (Months): 46.6
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of an investigational treatment (teduglutide) in Japanese patients with PN-dependent SBS. This study will also look at how teduglutide moves through the body (pharmacokinetics).

Condition or Disease	Intervention/Treatment	Phase
Short Bowel Syndrome	Drug: Teduglutide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 4-Stage, Open-label, Multicenter Study Including Long-term Extension to Evaluate the Safety, Efficacy and Pharmacokinetics of Teduglutide in Japanese Subjects With PN-dependent Short Bowel Syndrome
• Actual Study Start Date: Dec 18, 2014
• Actual Primary Completion Date: Nov 5, 2018
• Actual Study Completion Date: Nov 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 0.05 mg/kg/day administered by subcutaneous injection over a 24-week period.	Drug: Teduglutide; 0.05 mg/kg/day administered by subcutaneous injection over a 24-week period.

Outcome Measures

Primary Outcome Measures

1. Stage 2: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24 [Baseline (stage 2), Week 24]

   Absolute change from baseline in weekly PS volume at Week 24 was reported.

2. Stage 2: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24 [Baseline (stage 2), Week 24]

   Percent change from baseline in weekly PS volume at Week 24 was reported.

3. Stage 2: Percentage of Participants Who Demonstrate Response to Teduglutide at End of Stage 2 [End of Stage 2 (up to Week 24)]

   Response was defined as the achievement of at least a 20% reduction from baseline (Visit 2) in weekly PS volume at Week 20 and again at Week 24.

4. Stage 2: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Week 24 [Baseline (stage 2), Week 24]

   Absolute change from baseline in number of days per Week of PS usage at Week 24 was reported.

5. Stage 2: Absolute Change From Baseline in Plasma Citrulline Levels at Week 24 [Baseline (stage 2), Week 24]

   Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at Week 24 was reported.

6. Stage 2: Percent Change From Baseline in Plasma Citrulline Levels at Week 24 [Baseline (stage 2), Week 24]

   Plasma citrulline was measured as an assessment of enterocyte mass. Percent change from baseline in plasma citrulline at Week 24 was reported.

7. Stage 2: Number of Participants Who Achieved Enteral Autonomy at Week 24 [Week 24]

   Enteral autonomy was defined as no prescribed PS and no use of PS recorded in the participant diary at the end of stage 2. Number of participants who achieved enteral autonomy at Week 24 was reported.

8. Stage 3: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24 [Baseline (stage 3), Extension Month 24]

   Absolute change from baseline in weekly PS volume at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.

9. Stage 3: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24 [Baseline (stage 3), Extension Month 24]

   Percent change from baseline in weekly PS volume at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.

10. Stage 3: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Extension Month 24 [Baseline (stage 3), Extension Month 24]

    Absolute change from baseline in number of days per Week of PS usage at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.

11. Stage 3: Absolute Change From Baseline in Plasma Citrulline Levels at Extension Month 24 [Baseline (stage 3), Extension Month 24]

    Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.

12. Stage 3: Percent Change From Baseline in Plasma Citrulline Levels at Extension Month 24 [Baseline (stage 3), Extension Month 24]

    Plasma citrulline was measured as an assessment of enterocyte mass. Percent change from baseline in plasma citrulline at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.

13. Stage 4: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment [Baseline (stage 4), End of Treatment (up to 47 months)]

    Absolute change from baseline in weekly PS volume at end of treatment was reported.

14. Stage 4: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment [Baseline (stage 4), End of Treatment (up to 47 months)]

    Percent change from baseline in weekly PS volume at end of treatment was reported.

15. Stage 4: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment [Baseline (stage 4), End of Treatment (up to 47 months)]

    Absolute change from baseline in number of days per week of PS usage at end of treatment was reported.

16. Stage 4: Absolute Change From Baseline in Plasma Citrulline Levels at End of Treatment [Baseline (stage 4), End of Treatment (up to 47 months)]

    Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at end of treatment was reported.

17. Stage 4: Percent Change From Baseline in Plasma Citrulline Levels at End of Treatment [Baseline (stage 4), End of Treatment (up to 47 months)]

    Plasma citrulline was measured as an assessment of enterocyte mass. Percent change in plasma citrulline from baseline at end of treatment was reported.

Secondary Outcome Measures

1. Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-Inf) of Teduglutide in Plasma [Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose]

   Area under the concentration-time curve from time zero to infinity of teduglutide in plasma were evaluated.

2. Area Under the Concentration-Time Curve From Time Zero to the Last Time Point (AUC0-t) of Teduglutide in Plasma [Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose]

   Area under the concentration-time curve from time zero to the last time point of teduglutide in plasma were evaluated.

3. Maximum Concentration (Cmax) of Teduglutide in Plasma [Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose]

   Maximum concentration of teduglutide in plasma were evaluated.

4. Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma [Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose]

   Time to reach maximum observed drug concentration of teduglutide in plasma was evaluated.

5. Terminal Half-Life (t1/2) of Teduglutide in Plasma [Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose]

   Terminal half-life of teduglutide in plasma were evaluated.

6. Apparent Clearance (CL/F) of Teduglutide in Plasma [Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose]

   Apparent clearance of teduglutide in plasma were evaluated.

7. Apparent Volume of Distribution (Vz/F) of Teduglutide in Plasma [Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose]

   Apparent volume of distribution of teduglutide in plasma were evaluated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

This study has 3 stages, consisting of an optimization/stabilization period (Stage 1), a 24-week treatment period in which all patients will receive teduglutide (Stage 2), and a long-term extension (Stage 3).

During the long-term extension (Stage 3), patients will continue to receive teduglutide for up to an additional 24 months or until teduglutide is commercially available, whichever comes earlier.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tohoku University Hospital	Sendai	Aoba-ku	Japan	980-8574
2	Yokohama Municipal Citizen's Hospital	Yokohama	Hodogaya-ku	Japan	240-8555
3	Hospital of Hyogo College of Medicine	Hyogo	Nishinomiya	Japan	663-8501
4	Osaka University Hospital, Department of Gastroenterological Surgery	Osaka	Suita	Japan	565-0871
5	Osaka University Hospital, Department of Pediatric Surgery	Osaka	Suita	Japan	565-0871

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Apr 3, 2017
• Statistical Analysis Plan - Oct 29, 2018

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02340819
• Other Study ID Numbers: TED-C14-004
• First Posted: Jan 19, 2015
• Last Update Posted: Jun 9, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Short Bowel Syndrome; Syndrome; Teduglutide

Study Results

Participant Flow

Recruitment Details	The study was conducted at five centers in Japan between 18 December 2014 (first participant first visit) and 12 November 2018 (last participant last visit).
Pre-assignment Detail	Screened participants underwent a maximum 8 week parenteral support (PS) optimization period and 4 to 8 week stabilization period (stage 1) followed by 24 weeks treatment period (stage 2), and a long-term extension period were all participants received same treatment of stage 2 in stage 3 and stage 4. Total study duration was up to 47 months.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Period Title: Overall Study
STARTED	11
Started Stage 2	11
Completed Stage 2	9
Started Stage 3	8
Completed Stage 3	7
Started Stage 4	7
Completed Stage 4	7
COMPLETED	7
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Overall Participants	11
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.9 (12.41)
Sex: Female, Male (Count of Participants)
Female	3 27.3%
Male	8 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	11 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	11 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Stage 2: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
Description	Absolute change from baseline in weekly PS volume at Week 24 was reported.
Time Frame	Baseline (stage 2), Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	9
Mean (Standard Deviation) [Liter per week (L/week)]	-4.92 (4.749)

2. Primary Outcome

Title	Stage 2: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
Description	Percent change from baseline in weekly PS volume at Week 24 was reported.
Time Frame	Baseline (stage 2), Week 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	9
Mean (Standard Deviation) [Percent change in PS volume]	-30.07 (25.892)

3. Primary Outcome

Title	Stage 2: Percentage of Participants Who Demonstrate Response to Teduglutide at End of Stage 2
Description	Response was defined as the achievement of at least a 20% reduction from baseline (Visit 2) in weekly PS volume at Week 20 and again at Week 24.
Time Frame	End of Stage 2 (up to Week 24)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	11
PS Response: Yes	45.5 413.6%
PS Response: No	54.5 495.5%

4. Primary Outcome

Title	Stage 2: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Week 24
Description	Absolute change from baseline in number of days per Week of PS usage at Week 24 was reported.
Time Frame	Baseline (stage 2), Week 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	9
Mean (Standard Deviation) [Days per week (days/week)]	-1.0 (1.80)

5. Primary Outcome

Title	Stage 2: Absolute Change From Baseline in Plasma Citrulline Levels at Week 24
Description	Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at Week 24 was reported.
Time Frame	Baseline (stage 2), Week 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	9
Mean (Standard Deviation) [Micromoles per liter]	15.0 (17.37)

6. Primary Outcome

Title	Stage 2: Percent Change From Baseline in Plasma Citrulline Levels at Week 24
Description	Plasma citrulline was measured as an assessment of enterocyte mass. Percent change from baseline in plasma citrulline at Week 24 was reported.
Time Frame	Baseline (stage 2), Week 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	9
Mean (Standard Deviation) [Percent change]	86.9 (112.33)

7. Primary Outcome

Title	Stage 2: Number of Participants Who Achieved Enteral Autonomy at Week 24
Description	Enteral autonomy was defined as no prescribed PS and no use of PS recorded in the participant diary at the end of stage 2. Number of participants who achieved enteral autonomy at Week 24 was reported.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	11
Count of Participants [Participants]	0 0%

8. Primary Outcome

Title	Stage 3: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24
Description	Absolute change from baseline in weekly PS volume at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Time Frame	Baseline (stage 3), Extension Month 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	7
Mean (Standard Deviation) [L/week]	-8.33 (5.940)

9. Primary Outcome

Title	Stage 3: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24
Description	Percent change from baseline in weekly PS volume at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Time Frame	Baseline (stage 3), Extension Month 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	7
Mean (Standard Deviation) [Percent change in PS volume]	-53.53 (33.866)

10. Primary Outcome

Title	Stage 3: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Extension Month 24
Description	Absolute change from baseline in number of days per Week of PS usage at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Time Frame	Baseline (stage 3), Extension Month 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	7
Mean (Standard Deviation) [days/week]	-2.1 (3.34)

11. Primary Outcome

Title	Stage 3: Absolute Change From Baseline in Plasma Citrulline Levels at Extension Month 24
Description	Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Time Frame	Baseline (stage 3), Extension Month 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	7
Mean (Standard Deviation) [Micromoles per liter]	28.3 (24.05)

12. Primary Outcome

Title	Stage 3: Percent Change From Baseline in Plasma Citrulline Levels at Extension Month 24
Description	Plasma citrulline was measured as an assessment of enterocyte mass. Percent change from baseline in plasma citrulline at extension Month 24 was reported. Extension month 24 = 30 months of teduglutide treatment.
Time Frame	Baseline (stage 3), Extension Month 24

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	7
Mean (Standard Deviation) [Percent change]	135.0 (84.17)

13. Primary Outcome

Title	Stage 4: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment
Description	Absolute change from baseline in weekly PS volume at end of treatment was reported.
Time Frame	Baseline (stage 4), End of Treatment (up to 47 months)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	11
Mean (Standard Deviation) [L/week]	-5.08 (6.404)

14. Primary Outcome

Title	Stage 4: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment
Description	Percent change from baseline in weekly PS volume at end of treatment was reported.
Time Frame	Baseline (stage 4), End of Treatment (up to 47 months)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	11
Mean (Standard Deviation) [Percent change in PS volume]	-34.12 (38.877)

15. Primary Outcome

Title	Stage 4: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment
Description	Absolute change from baseline in number of days per week of PS usage at end of treatment was reported.
Time Frame	Baseline (stage 4), End of Treatment (up to 47 months)

Outcome Measure Data

Analysis Population Description

ITT population consists of all participants who were enrolled and eligible to enter Stage 2.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	11
Mean (Standard Deviation) [days/week]	-1.4 (2.80)

16. Primary Outcome

Title	Stage 4: Absolute Change From Baseline in Plasma Citrulline Levels at End of Treatment
Description	Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at end of treatment was reported.
Time Frame	Baseline (stage 4), End of Treatment (up to 47 months)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	11
Mean (Standard Deviation) [Micromoles per liter]	19.3 (19.96)

17. Primary Outcome

Title	Stage 4: Percent Change From Baseline in Plasma Citrulline Levels at End of Treatment
Description	Plasma citrulline was measured as an assessment of enterocyte mass. Percent change in plasma citrulline from baseline at end of treatment was reported.
Time Frame	Baseline (stage 4), End of Treatment (up to 47 months)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were enrolled and eligible to enter Stage 2.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	11
Mean (Standard Deviation) [Percent change]	110.3 (98.13)

18. Secondary Outcome

Title	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-Inf) of Teduglutide in Plasma
Description	Area under the concentration-time curve from time zero to infinity of teduglutide in plasma were evaluated.
Time Frame	Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	8
Mean (Standard Deviation) [Nanogram*hour per milliliter (ng*h/mL)]	204 (51.1)

19. Secondary Outcome

Title	Area Under the Concentration-Time Curve From Time Zero to the Last Time Point (AUC0-t) of Teduglutide in Plasma
Description	Area under the concentration-time curve from time zero to the last time point of teduglutide in plasma were evaluated.
Time Frame	Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	8
Mean (Standard Deviation) [ng*h/mL]	201 (51.6)

20. Secondary Outcome

Title	Maximum Concentration (Cmax) of Teduglutide in Plasma
Description	Maximum concentration of teduglutide in plasma were evaluated.
Time Frame	Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	8
Mean (Standard Deviation) [Nanogram per milliliter (ng/mL)]	49.7 (19.7)

21. Secondary Outcome

Title	Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma
Description	Time to reach maximum observed drug concentration of teduglutide in plasma was evaluated.
Time Frame	Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	8
Median (Full Range) [hour]	2.49

22. Secondary Outcome

Title	Terminal Half-Life (t1/2) of Teduglutide in Plasma
Description	Terminal half-life of teduglutide in plasma were evaluated.
Time Frame	Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	8
Median (Full Range) [hour]	1.06

23. Secondary Outcome

Title	Apparent Clearance (CL/F) of Teduglutide in Plasma
Description	Apparent clearance of teduglutide in plasma were evaluated.
Time Frame	Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data are considered sufficient and interpretable.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	8
Mean (Standard Deviation) [liter per hour (L/h)]	14.5 (4.09)

24. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of Teduglutide in Plasma
Description	Apparent volume of distribution of teduglutide in plasma were evaluated.
Time Frame	Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK analysis population was defined as all participants, at Stage 2, in the safety analysis population for whom the primary PK data were considered sufficient and interpretable.

Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
Measure Participants	8
Mean (Standard Deviation) [liter]	27.8 (22.5)

Adverse Events

Time Frame	From start of study treatment up to end of the study (up to 47 months)
Arm/Group Title	Teduglutide
Arm/Group Description	Optimized and stabilized participants received subcutaneous (SC) injection of teduglutide at a dose of 0.05 milligram per kilogram per day (mg/kg/day) once daily for 24 weeks during stage 2, an additional 24 months in stage 3 and continued (stage 4) until the participants entered the long-term extension study SHP633-307 (NCT03596164) or discontinued.
All Cause Mortality
	Teduglutide
	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)
Serious Adverse Events
	Teduglutide
	Affected / at Risk (%)	# Events
Total	7/11 (63.6%)
Gastrointestinal disorders
Enteritis	1/11 (9.1%)	1
Enterocolitis	1/11 (9.1%)	1
Intestinal obstruction	1/11 (9.1%)	1
General disorders
Device occlusion	1/11 (9.1%)	2
Pyrexia	1/11 (9.1%)	1
Hepatobiliary disorders
Acute hepatic failure	1/11 (9.1%)	1
Infections and infestations
Arthritis bacterial	1/11 (9.1%)	1
Catheter site infection	1/11 (9.1%)	1
Device related infection	7/11 (63.6%)	19
Sepsis	1/11 (9.1%)	1
Streptococcal infection	1/11 (9.1%)	1
Metabolism and nutrition disorders
Dehydration	1/11 (9.1%)	1
Renal and urinary disorders
Renal failure acute	1/11 (9.1%)	1
Vascular disorders
Thrombophlebitis	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Teduglutide
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Anaemia	1/11 (9.1%)	1
Disseminated intravascular coagulation	1/11 (9.1%)	1
Cardiac disorders
Cardiac failure acute	1/11 (9.1%)	1
Endocrine disorders
Thyroid cyst	1/11 (9.1%)	1
Eye disorders
Asthenopia	1/11 (9.1%)	2
Dry eye	1/11 (9.1%)	1
Eye oedema	1/11 (9.1%)	1
Vision blurred	1/11 (9.1%)	1
Vitreous opacities	1/11 (9.1%)	1
Gastrointestinal disorders
Abdominal distension	3/11 (27.3%)	3
Abdominal pain	4/11 (36.4%)	5
Abdominal pain upper	1/11 (9.1%)	1
Abdominal tenderness	1/11 (9.1%)	1
Cheilitis	1/11 (9.1%)	2
Constipation	1/11 (9.1%)	1
Dental caries	1/11 (9.1%)	1
Diarrhoea	3/11 (27.3%)	3
Dyspepsia	1/11 (9.1%)	1
Enterocolitis	1/11 (9.1%)	1
Epigastric discomfort	1/11 (9.1%)	1
Eructation	1/11 (9.1%)	2
Gingival pain	1/11 (9.1%)	1
Mouth haemorrhage	1/11 (9.1%)	1
Nausea	3/11 (27.3%)	7
Pancreatic duct dilatation	1/11 (9.1%)	1
Pancreatitis	1/11 (9.1%)	1
Proctalgia	1/11 (9.1%)	1
Stomatitis	3/11 (27.3%)	3
Toothache	1/11 (9.1%)	2
Vomiting	3/11 (27.3%)	3
General disorders
Catheter site inflammation	1/11 (9.1%)	1
Catheter site pain	2/11 (18.2%)	3
Chest pain	1/11 (9.1%)	1
Device occlusion	3/11 (27.3%)	4
Fatigue	1/11 (9.1%)	1
Hypothermia	1/11 (9.1%)	1
Injection site reaction	2/11 (18.2%)	2
Injury associated with device	1/11 (9.1%)	1
Malaise	1/11 (9.1%)	2
Oedema	1/11 (9.1%)	1
Puncture site pain	1/11 (9.1%)	1
Pyrexia	5/11 (45.5%)	7
Thirst	1/11 (9.1%)	2
Hepatobiliary disorders
Hyperbilirubinaemia	1/11 (9.1%)	1
Hyperplastic cholecystopathy	1/11 (9.1%)	1
Immune system disorders
Hypersensitivity	1/11 (9.1%)	1
Infections and infestations
Anal abscess	1/11 (9.1%)	1
Balanitis candida	1/11 (9.1%)	1
Catheter site infection	1/11 (9.1%)	1
Cellulitis	1/11 (9.1%)	1
Device related infection	2/11 (18.2%)	3
Gingivitis	1/11 (9.1%)	2
Influenza	2/11 (18.2%)	2
Nasopharyngitis	5/11 (45.5%)	15
Oral candidiasis	1/11 (9.1%)	1
Oral herpes	1/11 (9.1%)	1
Respiratory tract infection	1/11 (9.1%)	1
Trichophytosis	1/11 (9.1%)	1
Injury, poisoning and procedural complications
Procedural pain	1/11 (9.1%)	1
Stoma site reaction	1/11 (9.1%)	1
Investigations
Blood alkaline phosphatase increased	1/11 (9.1%)	1
Blood creatinine increased	1/11 (9.1%)	1
C-reactive protein increased	1/11 (9.1%)	1
Carcinoembryonic antigen increased	1/11 (9.1%)	1
Intestinal transit time increased	1/11 (9.1%)	1
Lipase increased	1/11 (9.1%)	1
Liver function test abnormal	1/11 (9.1%)	1
Oxygen saturation decreased	1/11 (9.1%)	1
Platelet count decreased	1/11 (9.1%)	2
Urine output decreased	1/11 (9.1%)	1
Metabolism and nutrition disorders
Decreased appetite	1/11 (9.1%)	1
Dehydration	2/11 (18.2%)	3
Hyperglycaemia	1/11 (9.1%)	1
Hypoglycaemia	1/11 (9.1%)	1
Hypokalaemia	1/11 (9.1%)	1
Hypomagnesaemia	1/11 (9.1%)	1
Hypozincaemia	1/11 (9.1%)	1
Malnutrition	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	4/11 (36.4%)	4
Arthritis	1/11 (9.1%)	1
Back pain	1/11 (9.1%)	1
Muscle spasms	1/11 (9.1%)	1
Myalgia	1/11 (9.1%)	1
Polyarthritis	1/11 (9.1%)	1
Temporomandibular joint syndrome	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian adenoma	1/11 (9.1%)	1
Nervous system disorders
Amnesia	1/11 (9.1%)	1
Dizziness	1/11 (9.1%)	2
Dyslalia	1/11 (9.1%)	1
Headache	6/11 (54.5%)	10
Presyncope	1/11 (9.1%)	1
Somnolence	2/11 (18.2%)	2
Psychiatric disorders
Anxiety disorder	1/11 (9.1%)	1
Depression	1/11 (9.1%)	1
Insomnia	2/11 (18.2%)	2
Renal and urinary disorders
Haematuria	1/11 (9.1%)	1
Renal cyst	1/11 (9.1%)	1
Urinary incontinence	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/11 (9.1%)	1
Oropharyngeal pain	2/11 (18.2%)	2
Respiratory failure	1/11 (9.1%)	1
Rhinitis allergic	1/11 (9.1%)	1
Upper respiratory tract inflammation	2/11 (18.2%)	3
Skin and subcutaneous tissue disorders
Acne	1/11 (9.1%)	1
Dermal cyst	1/11 (9.1%)	1
Dermatitis contact	2/11 (18.2%)	2
Dry skin	1/11 (9.1%)	1
Erythema	1/11 (9.1%)	1
Pruritus	2/11 (18.2%)	2
Vascular disorders
Vascular pain	2/11 (18.2%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.