Trial Outcomes & Findings for Safety and Efficacy Study of Teduglutide in Subjects With Short Bowel Syndrome (NCT NCT00081458)

Last Updated: 2021-06-09

Results Overview

The intensity of the response relied on a reduction from Baseline in weekly parenteral nutrition (PN) volume (minimum reduction of 20% and a maximum of 100%). Duration of the response incorporated responses at Weeks(Wk) 16-20 and at Wk20-24. Zero (0 - lowest) assigned if \<20% reduction at Wk20-24 and reduction at Wk16-20 of \< 20%, 20-39%, or \>=40%. One (1) assigned if reduction of 20-39% at Wk20-24 but \< 20% at Wk16-20. Two(2) assigned if reductions of 40-99% at Wk20-24 AND \<20% at Wk16-20 OR 20-39% at Wk20-24 AND 20-39% at Wk16-20. Three (3) assigned if reductions of 100% at Wk20-24 AND \<20% at Wk16-20 OR 40-99% at Wk20-24 AND 20-39% at Wk16-20 OR 20-39% at Wk20-24 AND \>=40% at Wk16-20. Four (4) assigned if reductions of 100% at Wk20-24 AND 20-39% at Wk16-20 OR 40-99% at Wk20-24 AND \>=40% at Wk16-20.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

84 participants

Primary outcome timeframe

6 months

Results posted on

2021-06-09

Participant Flow

First subject was screened 25May2004 and last subject evaluations were completed on 06Jul2007.

Patients underwent stabilization period for parenteral nutrition prior to randomization

Participant milestones

Participant milestones
Measure	Placebo Placebo injected subcutaneously daily	Teduglutide 0.05 mg/kg/d teduglutide 0.05 mg/kg/d injected subcutaneously	Teduglutide 0.1 mg/kg/d teduglutide 0.1 mg/kg/d injected subcutaneously
Overall Study STARTED	16	35	33
Overall Study Received Treatment	16	35	32
Overall Study COMPLETED	15	27	29
Overall Study NOT COMPLETED	1	8	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo injected subcutaneously daily	Teduglutide 0.05 mg/kg/d teduglutide 0.05 mg/kg/d injected subcutaneously	Teduglutide 0.1 mg/kg/d teduglutide 0.1 mg/kg/d injected subcutaneously
Overall Study Adverse Event	1	5	2
Overall Study Withdrawal by Subject	0	3	1
Overall Study Randomized but not dosed	0	0	1

Baseline Characteristics

Safety and Efficacy Study of Teduglutide in Subjects With Short Bowel Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=16 Participants Placebo injected subcutaneously daily	Teduglutide 0.05 mg/kg/d n=35 Participants teduglutide 0.05 mg/kg/d injected subcutaneously	Teduglutide 0.1 mg/kg/d n=32 Participants teduglutide 0.1 mg/kg/d injected subcutaneously	Total n=83 Participants Total of all reporting groups
Age, Continuous	49.4 years STANDARD_DEVIATION 15.1 • n=99 Participants	47.1 years STANDARD_DEVIATION 14.2 • n=107 Participants	50.3 years STANDARD_DEVIATION 14.0 • n=206 Participants	48.8 years STANDARD_DEVIATION 14.2 • n=7 Participants
Age, Customized < 35 years	3 Participants n=99 Participants	7 Participants n=107 Participants	5 Participants n=206 Participants	15 Participants n=7 Participants
Age, Customized 35-44 years	2 Participants n=99 Participants	5 Participants n=107 Participants	4 Participants n=206 Participants	11 Participants n=7 Participants
Age, Customized 45 - 54 years	3 Participants n=99 Participants	12 Participants n=107 Participants	10 Participants n=206 Participants	25 Participants n=7 Participants
Age, Customized > 55 years	8 Participants n=99 Participants	11 Participants n=107 Participants	13 Participants n=206 Participants	32 Participants n=7 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	18 Participants n=107 Participants	19 Participants n=206 Participants	46 Participants n=7 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	17 Participants n=107 Participants	13 Participants n=206 Participants	37 Participants n=7 Participants
Region of Enrollment Belgium	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Region of Enrollment Canada	1 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants	8 Participants n=7 Participants
Region of Enrollment Denmark	2 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants	8 Participants n=7 Participants
Region of Enrollment France	2 Participants n=99 Participants	5 Participants n=107 Participants	2 Participants n=206 Participants	9 Participants n=7 Participants
Region of Enrollment Germany	0 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants	2 Participants n=7 Participants
Region of Enrollment Netherlands	0 Participants n=99 Participants	4 Participants n=107 Participants	1 Participants n=206 Participants	5 Participants n=7 Participants
Region of Enrollment Poland	3 Participants n=99 Participants	6 Participants n=107 Participants	8 Participants n=206 Participants	17 Participants n=7 Participants
Region of Enrollment United Kingdom	0 Participants n=99 Participants	3 Participants n=107 Participants	1 Participants n=206 Participants	4 Participants n=7 Participants
Region of Enrollment United States	7 Participants n=99 Participants	11 Participants n=107 Participants	10 Participants n=206 Participants	28 Participants n=7 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent to Treat (ITT) analysis using a stepdown procedure that was stopped if the 0.10 mg/kg dose was not significantly better than placebo.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Placebo injectable subcutaneously daily into the thigh or abdomen	Teduglutide 0.05 mg/kg/d n=35 Participants teduglutide 0.05 mg/kg/d injected subcutaneously	Teduglutide 0.1 mg/kg/d n=32 Participants teduglutide 0.1 mg/kg/d injected subcutaneously
A Graded Response Score in Parenteral Nutrition (PN) Reduction 0 (No Response)	15 participants	19 participants	24 participants
A Graded Response Score in Parenteral Nutrition (PN) Reduction 1	0 participants	6 participants	2 participants
A Graded Response Score in Parenteral Nutrition (PN) Reduction 2	1 participants	6 participants	4 participants
A Graded Response Score in Parenteral Nutrition (PN) Reduction 5 (No longer need PN)	0 participants	2 participants	0 participants
A Graded Response Score in Parenteral Nutrition (PN) Reduction 4	0 participants	2 participants	2 participants

SECONDARY outcome

Timeframe: 6 months of treatment

An efficacy responder was defined as achieving at least a 20% reduction from Baseline to Week 20 and maintained at Week 24 in weekly actual PN infusion volume.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Placebo injectable subcutaneously daily into the thigh or abdomen	Teduglutide 0.05 mg/kg/d n=35 Participants teduglutide 0.05 mg/kg/d injected subcutaneously	Teduglutide 0.1 mg/kg/d n=32 Participants teduglutide 0.1 mg/kg/d injected subcutaneously
Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24 Responder	1 participants Interval 0.0 to 18.1	16 participants Interval 29.2 to 62.2	8 participants Interval 10.0 to 40.0
Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24 Non-Responder	15 participants Interval 0.0 to 0.0	19 participants Interval 0.0 to 0.0	24 participants Interval 0.0 to 0.0

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 15 other events

Deaths: 0 deaths

Teduglutide 0.05 mg/kg/d

Serious events: 13 serious events

Other events: 33 other events

Deaths: 0 deaths

Teduglutide 0.1 mg/kg/d

Serious events: 11 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Placebo n=16 participants at risk Placebo injected subcutaneously daily	Teduglutide 0.05 mg/kg/d n=35 participants at risk teduglutide 0.05 mg/kg/d injected subcutaneously	Teduglutide 0.1 mg/kg/d n=32 participants at risk teduglutide 0.1 mg/kg/d injected subcutaneously
Gastrointestinal disorders abdominal distension	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	17.1% 6/35 • Number of events 7 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	9.4% 3/32 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Gastrointestinal disorders Abdominal pain	12.5% 2/16 • Number of events 2 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	20.0% 7/35 • Number of events 12 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	28.1% 9/32 • Number of events 11 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Gastrointestinal disorders diahrrea	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	0.00% 0/35 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	9.4% 3/32 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Gastrointestinal disorders Dyspepsia	6.2% 1/16 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	0.00% 0/35 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	9.4% 3/32 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Gastrointestinal disorders Nausea	25.0% 4/16 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	14.3% 5/35 • Number of events 7 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	31.2% 10/32 • Number of events 13 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Asthenia	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	8.6% 3/35 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	6.2% 2/32 • Number of events 2 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Catheter related complications	18.8% 3/16 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	2.9% 1/35 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	9.4% 3/32 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Fatigue	12.5% 2/16 • Number of events 2 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	2.9% 1/35 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	15.6% 5/32 • Number of events 7 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Injection site bruising	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	2.9% 1/35 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	21.9% 7/32 • Number of events 8 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Injection site erythema	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	2.9% 1/35 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	18.8% 6/32 • Number of events 6 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Injection site pain	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	0.00% 0/35 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	12.5% 4/32 • Number of events 5 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Pain	6.2% 1/16 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	0.00% 0/35 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	12.5% 4/32 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Gastrointestinal disorders Vomiting	12.5% 2/16 • Number of events 2 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	11.4% 4/35 • Number of events 8 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	18.8% 6/32 • Number of events 7 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	11.4% 4/35 • Number of events 5 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	6.2% 2/32 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
General disorders Pyrexia	6.2% 1/16 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	8.6% 3/35 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	9.4% 3/32 • Number of events 6 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Infections and infestations Catheter sepsis	12.5% 2/16 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	11.4% 4/35 • Number of events 12 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	12.5% 4/32 • Number of events 5 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Infections and infestations Catheter site infection	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	8.6% 3/35 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	3.1% 1/32 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Infections and infestations Influenza	6.2% 1/16 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	8.6% 3/35 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	12.5% 4/32 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Infections and infestations Nasopharyngitis	12.5% 2/16 • Number of events 2 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	17.1% 6/35 • Number of events 9 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	15.6% 5/32 • Number of events 7 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Infections and infestations Urinary tract infection	18.8% 3/16 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	8.6% 3/35 • Number of events 7 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	15.6% 5/32 • Number of events 6 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Injury, poisoning and procedural complications Intestinal stoma complications	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	2.9% 1/35 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	15.6% 5/32 • Number of events 5 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 1/16 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	5.7% 2/35 • Number of events 4 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	9.4% 3/32 • Number of events 5 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Number of events 2 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	0.00% 0/35 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	9.4% 3/32 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	25.7% 9/35 • Number of events 29 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	21.9% 7/32 • Number of events 12 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/16 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	8.6% 3/35 • Number of events 3 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.	3.1% 1/32 • Number of events 1 • 6 months A total of 84 subjects were randomized in this study; however, one subject did not receive study drug. Thus, the safety population consists of 83 subjects.