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
Overview
- Phase
- Phase 3
- Intervention
- Teduglutide
- Conditions
- Short Bowel Syndrome
- Sponsor
- Shire
- Enrollment
- 11
- Locations
- 5
- Primary Endpoint
- Stage 2: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm 1
0.05 mg/kg/day administered by subcutaneous injection over a 24-week period.
Intervention: Teduglutide
Outcomes
Primary Outcomes
Stage 2: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
Time Frame: Baseline (stage 2), Week 24
Percent change from baseline in weekly PS volume at Week 24 was reported.
Stage 2: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Week 24
Time Frame: Baseline (stage 2), Week 24
Absolute change from baseline in number of days per Week of PS usage at Week 24 was reported.
Stage 2: Number of Participants Who Achieved Enteral Autonomy at Week 24
Time Frame: 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.
Stage 2: Percent Change From Baseline in Plasma Citrulline Levels at Week 24
Time Frame: 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.
Stage 3: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24
Time Frame: 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.
Stage 3: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at Extension Month 24
Time Frame: 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.
Stage 2: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
Time Frame: Baseline (stage 2), Week 24
Absolute change from baseline in weekly PS volume at Week 24 was reported.
Stage 2: Percentage of Participants Who Demonstrate Response to Teduglutide at End of Stage 2
Time Frame: 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.
Stage 2: Absolute Change From Baseline in Plasma Citrulline Levels at Week 24
Time Frame: 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.
Stage 3: Absolute Change From Baseline in Plasma Citrulline Levels at Extension Month 24
Time Frame: 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.
Stage 3: Percent Change From Baseline in Plasma Citrulline Levels at Extension Month 24
Time Frame: 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.
Stage 3: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at Extension Month 24
Time Frame: 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.
Stage 4: Absolute Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment
Time Frame: Baseline (stage 4), End of Treatment (up to 47 months)
Absolute change from baseline in weekly PS volume at end of treatment was reported.
Stage 4: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment
Time Frame: Baseline (stage 4), End of Treatment (up to 47 months)
Percent change from baseline in weekly PS volume at end of treatment was reported.
Stage 4: Absolute Change From Baseline in Number of Days Per Week of Parenteral Support (PS) Usage at End of Treatment
Time Frame: 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.
Stage 4: Absolute Change From Baseline in Plasma Citrulline Levels at End of Treatment
Time Frame: 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.
Stage 4: Percent Change From Baseline in Plasma Citrulline Levels at End of Treatment
Time Frame: 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 Outcomes
- 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 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)
- Maximum Concentration (Cmax) 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 (Tmax) of Teduglutide in Plasma(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(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(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(Pre-dose, 15, 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dose)