Safety and Efficacy Study of Teduglutide in Subjects With... | NCT00081458

ID	Type	Description	Link
2004-000438-35	EudraCT Number

Label	Type	Description	Intervention Names
placebo	Placebo Comparator	Placebo injectable subcutaneously daily into the thigh or abdomen	Drug: Placebo
2	Experimental	teduglutide 0.05 mg/kg/d	Drug: Teduglutide 0.05 mg/kg/d
3	Experimental	teduglutide 0.1 mg/kg/d	Drug: Teduglutide 0.1 mg/kg/d

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	placebo injectable subcutaneously daily into thigh or abdomen	placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
A Graded Response Score in Parenteral Nutrition (PN) Reduction	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.	6 months

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24	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.	6 months of treatment

Eligibility Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Scottsdale		Scottsdale	Arizona	85259	United States
Georgetown University

PubMed Identifier	Type	Citation	Retractions
1904648	Background	Dudrick SJ, Latifi R, Fosnocht DE. Management of the short-bowel syndrome. Surg Clin North Am. 1991 Jun;71(3):625-43. doi: 10.1016/s0039-6109(16)45438-1.
3109044	Background	Rombeau JL, Rolandelli RH. Enteral and parenteral nutrition in patients with enteric fistulas and short bowel syndrome. Surg Clin North Am. 1987 Jun;67(3):551-71. doi: 10.1016/s0039-6109(16)44232-5.

ID	Title	Description
FG000	Placebo	Placebo injected subcutaneously daily
FG001	Teduglutide 0.05 mg/kg/d	teduglutide 0.05 mg/kg/d injected subcutaneously

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

A Graded Response Score in Parenteral Nutrition (PN) Reduction

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.

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.

Posted

Number

participants

6 months

ID	Title	Description
OG000	Placebo	Placebo injectable subcutaneously daily into the thigh or abdomen
OG001	Teduglutide 0.05 mg/kg/d	teduglutide 0.05 mg/kg/d injected subcutaneously
OG002	Teduglutide 0.1 mg/kg/d	teduglutide 0.1 mg/kg/d injected subcutaneously

Units	Counts
Participants	OG00016 OG00135 OG00232

Title

Denominators

Categories

0 (No Response)

Title	Measurements
	OG00015 OG00119 OG00224

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002		ANCOVA		0.007							95							Superiority or Other (legacy)

Secondary

Number of Subjects Achieving Binary Response at Week 20, Maintained at Week 24

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.

Posted

Number

participants

6 months of treatment

ID	Title	Description
OG000	Placebo	Placebo injected subcutaneously daily into the thigh or abdomen
OG001	Teduglutide 0.05 mg/kg/d	teduglutide 0.05 mg/kg/d injected subcutaneously
OG002	Teduglutide 0.1 mg/kg/d	teduglutide 0.1 mg/kg/d injected subcutaneously

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Cardiac failure congestive	Cardiac disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Colonic stenosis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Hemorrhoidal hemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Intestinal obstruction	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0021 events1 affected32 at risk
Pancreatitis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Short-bowel syndrome	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Small intestinal obstruction	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0021 events1 affected32 at risk
Catheter related complication	General disorders	Systematic Assessment	EG0003 events3 affected16 at risk EG0010 events0 affected35 at risk EG0023 events3 affected32 at risk
Pyrexia	General disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected35 at risk EG0020 events0 affected32 at risk
Cholecystitis	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events1 affected35 at risk EG0020 events0 affected32 at risk
Cholecystitis acute	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Gallbladder perforation	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0021 events1 affected32 at risk
Catheter bacteraemia	Infections and infestations	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events1 affected35 at risk EG0020 events0 affected32 at risk
Catheter related infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0021 events1 affected32 at risk
Catheter sepsis	Infections and infestations	Systematic Assessment	EG0003 events1 affected16 at risk EG00110 events3 affected35 at risk EG0025 events4 affected32 at risk
Catheter site infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected35 at risk EG0020 events0 affected32 at risk
Fungemia	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Infectious mononucleosis	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Meningitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events1 affected35 at risk EG0020 events0 affected32 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0014 events1 affected35 at risk EG0020 events0 affected32 at risk
Device failure	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected35 at risk EG0021 events1 affected32 at risk
Eye Injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected35 at risk EG0020 events0 affected32 at risk
Intestinal stoma complication	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0021 events1 affected32 at risk
Medical device complication	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Drug level increased	Investigations	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Heart rate increased	Investigations	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected35 at risk EG0020 events0 affected32 at risk
Intervertebral discitis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected35 at risk EG0020 events0 affected32 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0021 events1 affected32 at risk
Coma	Nervous system disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Hypersomnia	Nervous system disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0020 events0 affected32 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected35 at risk EG0020 events0 affected32 at risk
Catheterization venous	Surgical and medical procedures	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0021 events1 affected32 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
abdominal distension	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0017 events6 affected35 at risk EG0024 events3 affected32 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected16 at risk EG00112 events7 affected35 at risk EG00211 events9 affected32 at risk
diahrrea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0023 events3 affected32 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected35 at risk EG0024 events3 affected32 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected16 at risk EG0017 events5 affected35 at risk EG00213 events10 affected32 at risk
Asthenia	General disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0013 events3 affected35 at risk EG0022 events2 affected32 at risk
Catheter related complications	General disorders	Systematic Assessment	EG0003 events3 affected16 at risk EG0011 events1 affected35 at risk EG0024 events3 affected32 at risk
Fatigue	General disorders	Systematic Assessment	EG0002 events2 affected16 at risk EG0011 events1 affected35 at risk EG0027 events5 affected32 at risk
Injection site bruising	General disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0028 events7 affected32 at risk
Injection site erythema	General disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0026 events6 affected32 at risk
Injection site pain	General disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected35 at risk EG0025 events4 affected32 at risk
Pain	General disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected35 at risk EG0024 events4 affected32 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected16 at risk EG0018 events4 affected35 at risk EG0027 events6 affected32 at risk
Abdominal Pain Upper	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0015 events4 affected35 at risk EG0024 events2 affected32 at risk
Pyrexia	General disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG0013 events3 affected35 at risk EG0026 events3 affected32 at risk
Catheter sepsis	Infections and infestations	Systematic Assessment	EG0004 events2 affected16 at risk EG00112 events4 affected35 at risk EG0025 events4 affected32 at risk
Catheter site infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected16 at risk EG0013 events3 affected35 at risk EG0021 events1 affected32 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0001 events1 affected16 at risk EG0013 events3 affected35 at risk EG0024 events4 affected32 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0002 events2 affected16 at risk EG0019 events6 affected35 at risk EG0027 events5 affected32 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0003 events3 affected16 at risk EG0017 events3 affected35 at risk EG0026 events5 affected32 at risk
Intestinal stoma complications	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected35 at risk EG0025 events5 affected32 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG0014 events2 affected35 at risk EG0025 events3 affected32 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events1 affected16 at risk EG0010 events0 affected35 at risk EG0023 events3 affected32 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0001 events1 affected16 at risk EG00129 events9 affected35 at risk EG00212 events7 affected32 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected16 at risk EG0013 events3 affected35 at risk EG0021 events1 affected32 at risk

ID	Term
D012778	Short Bowel Syndrome
D006963	Hyperphagia

ID	Term
D008286	Malabsorption Syndromes
D007410	Intestinal Diseases
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D011183	Postoperative Complications
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms

ID	Title	Description
BG000	Placebo	Placebo injected subcutaneously daily
BG001	Teduglutide 0.05 mg/kg/d	teduglutide 0.05 mg/kg/d injected subcutaneously
BG002	Teduglutide 0.1 mg/kg/d	teduglutide 0.1 mg/kg/d injected subcutaneously
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo injected subcutaneously daily	5	16	15	16
EG001	Teduglutide 0.05 mg/kg/d	teduglutide 0.05 mg/kg/d injected subcutaneously	13	35	33	35
EG002	Teduglutide 0.1 mg/kg/d	teduglutide 0.1 mg/kg/d injected subcutaneously	11	32	31	32