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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Teduglutide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>0.05 mg/kg/day administered by subcutaneous injection over a 24-week period. | Drug: Teduglutide<br>* 0.05 mg/kg/day administered by subcutaneous injection over a 24-week period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stage 2: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24 | Absolute change from baseline in weekly PS volume at Week 24 was reported. | Baseline (stage 2), Week 24 | 
| Stage 2: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24 | Percent change from baseline in weekly PS volume at Week 24 was reported. | Baseline (stage 2), Week 24 | 
| Stage 2: Percentage of Participants Who Demonstrate Response to Teduglutide at End of Stage 2 | 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. | End of Stage 2 (up to Week 24) | 
| Stage 2: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Week 24 | Absolute change from baseline in number of days per Week of PS usage at Week 24 was reported. | Baseline (stage 2), Week 24 | 
| Stage 2: Absolute Change From Baseline in Plasma Citrulline Levels at 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. | Baseline (stage 2), Week 24 | 
| Stage 2: Percent Change From Baseline in Plasma Citrulline Levels at Week 24 | Plasma citrulline was measured as an assessment of enterocyte mass. Percent change from baseline in plasma citrulline at Week 24 was reported. | Baseline (stage 2), Week 24 | 
| Stage 2: Number of Participants Who Achieved Enteral Autonomy at 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. | Week 24 | 
| Stage 3: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at 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. | Baseline (stage 3), Extension Month 24 | 
| Stage 3: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at 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. | Baseline (stage 3), Extension Month 24 | 
| Stage 3: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at 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. | Baseline (stage 3), Extension Month 24 | 
| Stage 3: Absolute Change From Baseline in Plasma Citrulline Levels at 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. | Baseline (stage 3), Extension Month 24 | 
| Stage 3: Percent Change From Baseline in Plasma Citrulline Levels at 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. | Baseline (stage 3), Extension Month 24 | 
| Stage 4: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment | Absolute change from baseline in weekly PS volume at end of treatment was reported. | Baseline (stage 4), End of Treatment (up to 47 months) | 
| Stage 4: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment | Percent change from baseline in weekly PS volume at end of treatment was reported. | Baseline (stage 4), End of Treatment (up to 47 months) | 
| Stage 4: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment | Absolute change from baseline in number of days per week of PS usage at end of treatment was reported. | Baseline (stage 4), End of Treatment (up to 47 months) | 
| Stage 4: Absolute Change From Baseline in Plasma Citrulline Levels at End of Treatment | Plasma citrulline was measured as an assessment of enterocyte mass. Absolute change from baseline in plasma citrulline levels at end of treatment was reported. | Baseline (stage 4), End of Treatment (up to 47 months) | 
| Stage 4: Percent Change From Baseline in Plasma Citrulline Levels at End of Treatment | Plasma citrulline was measured as an assessment of enterocyte mass. Percent change in plasma citrulline from baseline at end of treatment was reported. | Baseline (stage 4), End of Treatment (up to 47 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-Inf) of Teduglutide in Plasma | Area under the concentration-time curve from time zero to infinity of teduglutide in plasma were evaluated. | 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 (AUC0-t) of Teduglutide in Plasma | Area under the concentration-time curve from time zero to the last time point of teduglutide in plasma were evaluated. | Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose | 
| Maximum Concentration (Cmax) of Teduglutide in Plasma | Maximum concentration of teduglutide in plasma were evaluated. | Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose | 
| Time to Reach Maximum Observed Drug Concentration (Tmax) of Teduglutide in Plasma | Time to reach maximum observed drug concentration of teduglutide in plasma was evaluated. | Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose | 
| Terminal Half-Life (t1/2) of Teduglutide in Plasma | Terminal half-life of teduglutide in plasma were evaluated. | Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose | 
| Apparent Clearance (CL/F) of Teduglutide in Plasma | Apparent clearance of teduglutide in plasma were evaluated. | Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose | 
| Apparent Volume of Distribution (Vz/F) of Teduglutide in Plasma | Apparent volume of distribution of teduglutide in plasma were evaluated. | Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose |