Study of Teduglutide in Japanese Participants With Short Bowel Syndrome

Study Overview
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Brief Summary
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The objectives of this clinical study are to evaluate the safety, efficacy, and pharmacokinetics (PK) of teduglutide in Japanese participants with short bowel syndrome (SBS) who are dependent on parenteral nutrition/intravenous (PN/IV) over a 24-week treatment period.

Official Title
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A 24-Week Safety, Efficacy, Pharmacokinetic Study of Teduglutide in Japanese Subjects With Short Bowel Syndrome Who Are Dependent on Parenteral Support

Conditions
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Short Bowel Syndrome

Intervention / Treatment
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* Drug: Teduglutide
* Device: Syringe
* Device: Needle
* Device: Vial Adapter for Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to voluntarily provide written, signed, and informed consent to participate in the study. Male or female 16 years of age or older at the time of signing informed consent. Intestinal failure due to short bowel syndrome (SBS) as a result of major intestinal resection (example, due to injury, volvulus, vascular disease, cancer, Crohn's disease) that resulted in at least 12 continuous months of parenteral nutrition/intravenous (PN/IV) dependence at the time of informed consent. Parenteral nutrition requirement of at least 3 times per week during the week before the screening visit and during the 2 weeks prior to the baseline visit. Stable PN/IV requirement for at least 4 consecutive weeks immediately prior to the start of teduglutide treatment. Stability is defined as: a. Actual PN/IV usage is similar to prescribed PN/IV; b. Baseline (Visit 2) 48-hour oral fluid intake and urine output (I/O) volumes fall within +/- 25 percent (%) of the respective 48-hour I/O volumes at the last optimization visit; c. Urine output volume should NOT fall below 2 liter (L) and should not exceed 4 L per 48 hours at the last optimization visit, the stabilization visit, and the baseline visit. For participants with a history of Crohn's disease, clinical remission for at least 12 weeks prior to the baseline visit as demonstrated by clinical assessment, which may include procedure-based evidence of remission. Females of childbearing potential must agree to comply with the contraceptive requirements of the protocol. An understanding, ability, and willingness to fully comply with study procedures and restrictions. Exclusion Criteria: Participation in a clinical study using an experimental drug within 30 days or 5.5 halflives, whichever is longer, prior to screening, or concurrent participation in any other clinical study. Use of glucagon-like peptide (GLP)-2 or human growth hormone or analogs of these hormones within the past 6 months. Use of octreotide, GLP-1 analogs, dipeptidyl peptidase-IV inhibitors, or enteral glutamine within 30 days. Previous use of teduglutide. Participants with active inflammatory bowel disease (IBD) or participants with IBD who received a change in immunosuppressant therapy (example, azathioprine, anti- tumor necrosis factor (TNFs)) within the past 6 months. Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, familial adenomatous polyposis, etc. Chronic intestinal pseudo-obstruction or severe dysmotility. Clinically significant intestinal stenosis or obstruction, or evidence of such on upper gastrointestinal (GI) series with small bowel follow-through, within the past 6 months. Major GI surgical intervention, including bowel lengthening procedures, within the past 3 months (insertion of feeding tube or endoscopic procedure is allowed). Unstable cardiac disease, (example, congestive heart failure, cyanotic disease, or congenital heart disease). Moderate or severe renal impairment, defined as creatinine clearance less than (<) 50 millilitre (ml)/ minute (min). Currently diagnosed with cancer or a history of any cancer except surgically curative skin cancer within the past 5 years. Severe hepatobiliary disease including: a. Total bilirubin level greater than or equal to (>=) 2 times the upper limit of normal (ULN); b. Aspartate aminotransferase (AST) >=5 times ULN; c. Alanine aminotransferase (ALT) >=5 times ULN. Active clinically significant pancreatic disease, including clinical signs of pancreatitis associated with elevations in serum amylase or lipase >=2 times ULN. More than 4 SBS-related or PN/IV-related hospital admissions (example, central line associated bloodstream infection, bowel obstruction, severe fluid/electrolyte disturbances) within the past 12 months. Unscheduled hospitalization within 30 days prior to screening. Pregnant or lactating female. Any condition or circumstance that in the investigator's opinion put the participant at any undue risk, prevent completion of the study, or interfere with analysis of the study results.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teduglutide 0.05 mg<br>Participants will receive teduglutide 0.05 milligram per kilogram (mg/kg) subcutaneous (SC) injection once daily into 1 of the 4 quadrants of the abdomen or either thigh or arm for 24 weeks. | Drug: Teduglutide<br>* Teduglutide 0.05 mg/kg SC injection will be administered once daily into 1 of the 4 quadrants of the abdomen or either thigh or arm.<br>Device: Syringe<br>* Teduglutide will be administered using syringe. Syringe is approved for use in Japan by Pharmaceuticals and Medical Devices Agency (PMDA).<br>Device: Needle<br>* Teduglutide will be administered using needle. Needle is approved for use in Japan by PMDA.<br>Device: Vial Adapter for Device<br>* Vial adapter for device is approved for use in Japan by PMDA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Change from baseline in weekly PS volume at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET) | Percent change from baseline in weekly PS volume at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 20 | Percentage of participants who achieved at least 20% reduction from baseline in weekly PS volume at Week 20 was reported. | Baseline, Week 20 | 
| Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 24 | Percentage of participants who achieved at least 20% reduction from baseline in weekly PS volume at Week 24 was reported. | Baseline, Week 24 | 
| Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET) | Percentage of participants who achieve at least 20% reduction from baseline in weekly PS at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Days Per Week of Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET) | Change from baseline in days per week of PS at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Plasma Citrulline Levels at End of Treatment/Early Termination (EOT/ET) | Plasma citrulline levels were measured as a biomarker of enterocyte mass. Change from baseline in plasma citrulline levels up to EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Number of Participants Who Were Completely Weaned Off Parenteral Support (PS) at Week 24/End of Treatment (EOT) | Number of participants who were completely weaned off PS at Week 24/EOT was reported. | Week 24/EOT | 
| Area Under the Plasma Concentration-Time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Teduglutide | AUC0-t of teduglutide was reported. | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | 
| Maximum Plasma Concentration (Cmax) of Teduglutide | Cmax of teduglutide was reported. | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | 
| Time to Maximum Plasma Concentration (Tmax) of Teduglutide | Tmax of teduglutide was reported. | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | 
| Terminal-phase Half-life (T1/2) of Teduglutide | T1/2 of teduglutide was reported. | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | 
| Apparent Clearance (CL/F) of Teduglutide | CL/F of teduglutide was reported. | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | 
| Apparent Volume of Distribution (Vz/F) of Teduglutide | Vz/F of teduglutide was reported. | Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours Post-dose on Day 1; Pre-dose, 1, 2 hours Post-dose on Week 4 or Week 12 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs whose onset occurred, severity worsened, or intensity increased after receiving the study medication. | From start of study drug administration up to EOT/ET (up to Week 28) | 
| Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) | 12-lead ECG was performed at the study center after the participant has been resting for at least 5 minutes. Number of participants with clinically significant abnormalities in 12-Lead ECG was reported. | From start of study drug administration up to EOT/ET (up to Week 28) | 
| Change From Baseline in Blood Pressure at End of Treatment/Early Termination (EOT/ET) | Change from baseline in systolic and diastolic blood pressure at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Pulse Rate at End of Treatment/Early Termination (EOT/ET) | Change from baseline in pulse rate at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Body Temperature at End of Treatment/Early Termination (EOT/ET) | Change from baseline in body temperature at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Hemoglobin at End of Treatment/Early Termination (EOT/ET) | Change from baseline in hemoglobin at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Hematocrit at End of Treatment/Early Termination (EOT/ET) | Change from baseline in hematocrit at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Serum Blood Urea Nitrogen (BUN) at End of Treatment/Early Termination (EOT/ET) | Change from baseline in serum blood urea nitrogen at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Creatinine at End of Treatment/Early Termination (EOT/ET) | Change from baseline in creatinine at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Urine Sodium at End of Treatment/Early Termination (EOT/ET) | Change from baseline in urine sodium at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Number of Participants Who Reported Positive Specific Antibodies to Teduglutide at End of Treatment/Early Termination (EOT/ET) | Number of participants who reported positive specific antibodies to teduglutide at EOT/ET was reported. | EOT/ET (up to Week 28) | 
| Change From Baseline in 48-Hour Urine Output at End of Treatment/Early Termination (EOT/ET) | Change from baseline in 48-hour urine output at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Body Weight at End of Treatment/Early Termination (EOT/ET) | Change from baseline in body weight at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Change From Baseline in Body Mass Index (BMI) at End of Treatment/Early Termination (EOT/ET) | Change from baseline in BMI at EOT/ET was reported. | Baseline, EOT/ET (up to Week 28) | 
| Number of Participants With Abnormal Clinically Significant Changes in Gastrointestinal (GI) Specific Tests at Week 24/ET (Early Termination) | GI specific tests included colonoscopy or sigmoidoscopy, abdominal ultrasound, upper GI series with small bowel follow-through (UGI/SBFT). Number of participants with abnormal clinically significant changes in gastrointestinal specific tests at Week 24/ET was reported. | Week 24/ET |