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Study of Teduglutide in Japanese Participants With Short Bowel Syndrome

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ClinicalTrials.gov Identifier: NCT03663582
Recruitment Status : Active, not recruiting
First Posted : September 10, 2018
Last Update Posted : April 1, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Short Bowel Syndrome Drug: Teduglutide Device: Syringe Device: Needle Device: Vial Adapter for Device Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 24-Week Safety, Efficacy, Pharmacokinetic Study of Teduglutide in Japanese Subjects With Short Bowel Syndrome Who Are Dependent on Parenteral Support
Actual Study Start Date : October 29, 2018
Estimated Primary Completion Date : August 16, 2019
Estimated Study Completion Date : August 16, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Teduglutide

Arm Intervention/treatment
Experimental: Teduglutide 0.05 mg
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
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.

Device: Syringe
Teduglutide will be administered using syringe. Syringe is approved for use in Japan by Pharmaceuticals and Medical Devices Agency (PMDA).

Device: Needle
Teduglutide will be administered using needle. Needle is approved for use in Japan by PMDA.

Device: Vial Adapter for Device
Vial adapter for device is approved for use in Japan by PMDA.




Primary Outcome Measures :
  1. Absolute Change From Baseline in Weekly Parenteral Nutrition/Intravenous (PN/IV) Volume [ Time Frame: Baseline to each study visit until End of the treatment (Week 24) ]
    Absolute change in PN/IV volume will be assessed.

  2. Relative Change From Baseline in Weekly Parenteral Nutrition/Intravenous (PN/IV) Volume [ Time Frame: Baseline to each study visit until End of the treatment (Week 24) ]
    Relative change in PN/IV volume will be assessed.

  3. Percentage of Participants Who Achieve at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Nutrition/Intravenous (PN/IV) Volume Reduction at Week 20 [ Time Frame: Baseline, Week 20 ]
    Percentage of participants who achieve at least 20 percent (%) reduction from baseline in weekly parenteral nutrition/intravenous will be assessed.

  4. Percentage of Participants Who Achieve at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Nutrition/Intravenous (PN/IV) Volume Reduction at Week 24 [ Time Frame: Baseline, Week 24 ]
    Percentage of participants who achieve at least 20 percent (%) reduction from baseline in weekly parenteral nutrition/intravenous will be assessed.

  5. Percentage of Participants Who Achieve at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Nutrition/Intravenous (PN/IV) [ Time Frame: Baseline to each study visit until end of the treatment (Week 24) ]
    Percentage of participants who achieve at least 20 percent (%) reduction from baseline in weekly parenteral nutrition/intravenous will be assessed.

  6. Change in Days per Week of Parenteral Nutrition/Intravenous (PN/IV) Support [ Time Frame: Baseline to each study visit until end of the treatment (Week 24) ]
    Change in days per week of PN/IV support will be assessed.

  7. Change from Baseline in Plasma Citrulline Levels [ Time Frame: Baseline to each study visit until end of the treatment (Week 24) ]
    Plasma citrulline will be measured as an assessment of enterocyte mass.

  8. Number of Participants who Completely Wean off Parenteral Nutrition Intravenous (PN/IV) Support [ Time Frame: Week 24 ]
    Number of participants who completely wean off parenteral nutrition intravenous (PN/IV) support will be assessed.

  9. Area Under the Plasma Concentration-Time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Teduglutide [ Time Frame: Baseline: Predose, 15, 30 minutes (m), 1, 2, 3, 4, 6, 8, 10 and 12 hours (h) post dose; Week 4 or 12: Predose, 1, 2h post dose ]
    The AUC0-t of teduglutide will be assessed.

  10. Maximum Plasma Concentration (Cmax) of Teduglutide [ Time Frame: Baseline: Predose, 15, 30m, 1, 2, 3, 4, 6, 8, 10 and 12h post dose; Week 4 or 12: Predose, 1, 2h post dose ]
    The Cmax of teduglutide will be assessed.

  11. Time to Maximum Plasma Concentration (tmax) of Teduglutide [ Time Frame: Baseline: Predose, 15, 30m, 1, 2, 3, 4, 6, 8, 10 and 12h post dose; Week 4 or 12: Predose, 1, 2h post dose ]
    The tmax of teduglutide will be assessed.

  12. Terminal-phase Half-life (t1/2) of Teduglutide [ Time Frame: Baseline: Predose, 15, 30m, 1, 2, 3, 4, 6, 8, 10 and 12h post dose; Week 4 or 12: Predose, 1, 2h post dose ]
    The t1/2 of teduglutide will be assessed.

  13. Apparent Clearance (CL/F) of Teduglutide [ Time Frame: Baseline: Predose, 15, 30m, 1, 2, 3, 4, 6, 8, 10 and 12h post dose; Week 4 or 12: Predose, 1, 2h post dose ]
    The CL/F of teduglutide will be assessed.

  14. Apparent Volume of Distribution (V/F) of Teduglutide [ Time Frame: Baseline: Predose, 15, 30m, 1, 2, 3, 4, 6, 8, 10 and 12h post dose; Week 4 or 12: Predose, 1, 2h post dose ]
    The V/F of teduglutide will be assessed.

  15. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline to end of the study (Week 28) ]
    An adverse event (AE) is 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. The TEAEs are defined as AEs that started or worsened on or after the date and time of the first dose of study dose.

  16. Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) [ Time Frame: Baseline up to Week 24 ]
    A 12-lead ECG will be performed at the study center after the participant has been resting for at least 5 minutes. Number of participants with clinically significant changes in 12-Lead Electrocardiogram (ECG) will be reported.

  17. Change From Baseline in Blood Pressure [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in blood pressure will be reported.

  18. Change From Baseline in Pulse Rate [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in pulse rate will be reported.

  19. Change From Baseline in Body Temperature [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in body temperature will be reported.

  20. Change From Baseline in Hemoglobin [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in hemoglobin will be reported.

  21. Change From Baseline in Hematocrit [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in hematocrit will be reported.

  22. Change From Baseline in Serum Blood Urea Nitrogen [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in serum blood urea nitrogen will be reported

  23. Change From Baseline in Creatinine [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in creatinine will be reported.

  24. Change From Baseline in Urine Sodium [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in urine sodium will be reported

  25. Number of Participants Who Report Positive Specific Antibodies to Teduglutide [ Time Frame: Baseline up to Week 24 ]
    Number of participants who report positive specific antibodies to teduglutide will be reported.

  26. Change From Baseline in 48-Hour Urine Output [ Time Frame: Baseline to each study visit until end of the treatment (Week 24) ]
    Change from baseline in urine output will be assessed.

  27. Change From Baseline in Body Weight [ Time Frame: Baseline up to Week 24 ]
    Change from baseline in body weight will be reported.

  28. Change From Baseline in Body Mass Index (BMI) [ Time Frame: Baseline up to Week 24 ]
    Weight and height will be combined to report BMI in kilograms per square meter (kg/m^2). Change from baseline in BMI will be reported.

  29. Number of Participants With Abnormal Findings in Gastrointestinal (GI) Specific Tests [ Time Frame: Week 24 ]
    The GI specific tests includes colonoscopy or sigmoidoscopy, abdominal ultrasound, upper GI series with small bowel follow-through (UGI/SBFT).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Ability to voluntarily provide written, signed, and informed consent to participate in the study.
  2. Male or female 16 years of age or older at the time of signing informed consent.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Females of childbearing potential must agree to comply with the contraceptive requirements of the protocol.
  8. An understanding, ability, and willingness to fully comply with study procedures and restrictions.

Exclusion Criteria:

  1. 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.
  2. Use of glucagon-like peptide (GLP)-2 or human growth hormone or analogs of these hormones within the past 6 months.
  3. Use of octreotide, GLP-1 analogs, dipeptidyl peptidase-IV inhibitors, or enteral glutamine within 30 days.
  4. Previous use of teduglutide.
  5. 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.
  6. Intestinal malabsorption due to a genetic condition, such as cystic fibrosis, microvillus inclusion disease, familial adenomatous polyposis, etc.
  7. Chronic intestinal pseudo-obstruction or severe dysmotility.
  8. 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.
  9. Major GI surgical intervention, including bowel lengthening procedures, within the past 3 months (insertion of feeding tube or endoscopic procedure is allowed).
  10. Unstable cardiac disease, (example, congestive heart failure, cyanotic disease, or congenital heart disease).
  11. Moderate or severe renal impairment, defined as creatinine clearance less than (<) 50 millilitre (ml)/ minute (min).
  12. Currently diagnosed with cancer or a history of any cancer except surgically curative skin cancer within the past 5 years.
  13. 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.
  14. Active clinically significant pancreatic disease, including clinical signs of pancreatitis associated with elevations in serum amylase or lipase >=2 times ULN.
  15. 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.
  16. Unscheduled hospitalization within 30 days prior to screening.
  17. Pregnant or lactating female.
  18. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03663582


Locations
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Japan
Hiroshima University Hospital
Hiroshima-shi, Hiroshima-ken, Japan, 734-8551
Hyogo College of Medicine Hospital
Hyogo, Japan, 663-8501
Tohoku University Hospital
Miyagi-Ken, Japan, 980-8574
Osaka University Hospital
Osaka, Japan, 565-0871
Yokohama Municipal Citizen's Hospital
Yokohama, Japan, 240-8555
Sponsors and Collaborators
Shire
Investigators
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Study Director: Study Director Shire

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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03663582     History of Changes
Other Study ID Numbers: SHP633-306
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
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, …).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Syndrome
Short Bowel 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