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

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

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).

Study Overview

• Status: Completed
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: Teduglutide

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aoba-ku
    • Sendai, Aoba-ku, Japan, 980-8574
      • Tohoku University Hospital
  • Hodogaya-ku
    • Yokohama, Hodogaya-ku, Japan, 240-8555
      • Yokohama Municipal Citizen's Hospital
  • Nishinomiya
    • Hyogo, Nishinomiya, Japan, 663-8501
      • Hospital of Hyogo College of Medicine
  • Suita
    • Osaka, Suita, Japan, 565-0871
      • Osaka University Hospital, Department of Gastroenterological Surgery
    • Osaka, Suita, Japan, 565-0871
      • Osaka University Hospital, Department of Pediatric Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2014
• Primary Completion (ACTUAL): November 5, 2018
• Study Completion (ACTUAL): November 5, 2018

Study Registration Dates

• First Submitted: November 13, 2014
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (ESTIMATE): January 19, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Disease; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Syndrome; Short Bowel Syndrome; Physiological Effects of Drugs; Gastrointestinal Agents; Protective Agents; Radiation-Protective Agents; Teduglutide
• Other Study ID Numbers: TED-C14-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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, …)