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

• ClinicalTrials.gov Identifier: NCT02340819
• Recruitment Status: Completed
• First Posted: January 19, 2015
• Results First Posted: November 20, 2019
• Last Update Posted: June 9, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

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 (Clinical Trial)
• 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: December 18, 2014
• Actual Primary Completion Date: November 5, 2018
• Actual Study Completion Date: November 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 [ Time Frame: 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 [ Time Frame: 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 [ 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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 Outcome Measures :

1. Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-Inf) of Teduglutide in Plasma [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Japan

Tohoku University Hospital

Sendai, Aoba-ku, Japan, 980-8574

Yokohama Municipal Citizen's Hospital

Yokohama, Hodogaya-ku, Japan, 240-8555

Hospital of Hyogo College of Medicine

Hyogo, Nishinomiya, Japan, 663-8501

Osaka University Hospital, Department of Gastroenterological Surgery

Osaka, Suita, Japan, 565-0871

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)

Documents provided by Takeda ( Shire ):

Study Protocol  [PDF] April 3, 2017

Statistical Analysis Plan  [PDF] October 29, 2018

More Information

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02340819
• Other Study ID Numbers: TED-C14-004
• First Posted: January 19, 2015
• Results First Posted: November 20, 2019
• Last Update Posted: June 9, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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, …)

Additional relevant MeSH terms:

Short Bowel Syndrome; Syndrome; Disease; Pathologic Processes; Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Teduglutide; Gastrointestinal Agents; Radiation-Protective Agents; Protective Agents; Physiological Effects of Drugs