Clinical trial NCT03663582: Study of Teduglutide in Japanese Participants With Short Bowel Syndrome
Official title: A 24-Week Safety, Efficacy, Pharmacokinetic Study of Teduglutide in Japanese Subjects With Short Bowel Syndrome Who Are Dependent on Parenteral Support
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-09-10
Enrollment: 7
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Percent Change From Baseline in Weekly Parenteral Support (PS) Volume at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 20
timeFrame: Baseline, Week 20
measure: Percentage of Participants Who Achieved at Least 20 Percent (%) Reduction From Baseline in Weekly Parenteral Support (PS) Volume at Week 24
timeFrame: Baseline, Week 24
measure: 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)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Days Per Week of Parenteral Support (PS) at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Plasma Citrulline Levels at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Number of Participants Who Were Completely Weaned Off Parenteral Support (PS) at Week 24/End of Treatment (EOT)
timeFrame: Week 24/EOT
measure: Area Under the Plasma Concentration-Time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Teduglutide
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of Teduglutide
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of Teduglutide
timeFrame: 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
measure: Terminal-phase Half-life (T1/2) of Teduglutide
timeFrame: 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
measure: Apparent Clearance (CL/F) of Teduglutide
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of Teduglutide
timeFrame: 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
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to EOT/ET (up to Week 28)
measure: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG)
timeFrame: From start of study drug administration up to EOT/ET (up to Week 28)
measure: Change From Baseline in Blood Pressure at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Pulse Rate at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Body Temperature at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Hemoglobin at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Hematocrit at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Serum Blood Urea Nitrogen (BUN) at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Creatinine at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Urine Sodium at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Number of Participants Who Reported Positive Specific Antibodies to Teduglutide at End of Treatment/Early Termination (EOT/ET)
timeFrame: EOT/ET (up to Week 28)
measure: Change From Baseline in 48-Hour Urine Output at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Body Weight at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Change From Baseline in Body Mass Index (BMI) at End of Treatment/Early Termination (EOT/ET)
timeFrame: Baseline, EOT/ET (up to Week 28)
measure: Number of Participants With Abnormal Clinically Significant Changes in Gastrointestinal (GI) Specific Tests at Week 24/ET (Early Termination)
timeFrame: Week 24/ET
Secondary outcomes:
Other outcomes:
Locations:
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima-ken
city: Hyogo
country: Japan
facility: Hyogo College of Medicine Hospital
city: Miyagi-Ken
country: Japan
facility: Tohoku University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Yokohama
country: Japan
facility: Yokohama Municipal Citizen's Hospital
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: