Short bowel syndrome (SBS)
Conditions
Interventions
investigational material(s)
Generic name etc : Teduglutide
INN of investigational material : Teduglutide
Therapeutic category code : 249 Other hormone preparations (including antihormone preparation
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who met all of the following criteria were eligible for inclusion in the study: 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 SBS as a result of major intestinal resection (e.g. due to injury, volvulus, vascular disease, cancer, Crohns disease) that resulted in at least 12 continuous months of 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: 1) Actual PN/IV usage is similar to prescribed PN/IV. 2) Baseline (Visit 2) 48-hour oral fluid intake and urine output (I/O) volumes fall within +/-25% of the respective 48-hour I/O volumes at the last optimization visit. 3) Urine output volume should NOT fall below 2 L and should not exceed 4 L per 48 hours at the last optimization visit, the stabilization visit, and the baseline visit. 6. For subjects with a history of Crohns 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
Exclusion criteria: Exclusion Criteria: 1. Participation in a clinical study using an experimental drug within 30 days or 5.5 half-lives, 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 (=) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy 1.Number of Participants who Demonstrate at least 20 Percent (%) Reduction From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume Time Frame: Baseline to each study visit until End of study (3 years) Number of participants who demonstrate at least 20% reduction in PN/IV volume will be assessed. efficacy 2.Absolute Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume Time Frame: Baseline to each study visit until End of study (3 years) Absolute change in PN/IV volume will be assessed. efficacy 3.Relative Change From Baseline in Parenteral Nutrition Intravenous (PN/IV) Volume Time Frame: Baseline to each study visit until End of study (3 years) Relative change in PN/IV volume will be assessed. efficacy 4.Number of Participants who Completely Wean off Parenteral Nutrition Intravenous (PN/IV) Support Time Frame: Baseline, End of the study (3 years) Number of participants who completely wean off PN/IV support will be assessed. efficacy 5.Change From Baseline in Days per Week of Parenteral Nutrition Intravenous (PN/IV) Support Time Frame: Baseline to each study visit until End of study (3 years) Change in days per week of PN/IV will be assessed. efficacy 6.Change From Baseline in Plasma Citrulline Time Frame: Baseline to each study visit until End of study (3 years) Change in plasma citrulline will be assessed. safety 7.Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Time Frame: From start of study treatment up to End of study (3 years) 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. TEAEs are defined as AEs that start or deteriorate on or after the date of the first dose of investigational product. | — |
Secondary
| Measure | Time frame |
|---|---|
| safety 8.Change From Baseline in Blood Pressure Time Frame: Baseline to each study visit until End of study (3 years) Change in blood pressure will be assessed. pharmacokinetics 9.Area Under the Plasma Concentration-Time Curve From Zero to the Last Measurable Concentration (AUC0-t) of Teduglutide Time Frame: 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 AUC0-t of teduglutide was reported. pharmacokinetics 10.Maximum Plasma Concentration (Cmax) of Teduglutide Time Frame: 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 Cmax of teduglutide was reported. pharmacokinetics 11.Time to Maximum Plasma Concentration (Tmax) of Teduglutide Time Frame: 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 Tmax of teduglutide was reported. safety pharmacokinetics 12.Terminal-phase Half-life (T1/2) of Teduglutide Time Frame: 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 T1/2 of teduglutide was reported. pharmacokinetics 13.Apparent Clearance (CL/F) of Teduglutide Time Frame: 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 CL/F of teduglutide was reported. pharmacokinetics 13.Apparent Clearance (CL/F) of Teduglutide Time Frame: 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 CL/F of teduglutide was reported. pharmacokinetics 14.Apparent Volume of Distribution (Vz/F) of Teduglutide Time Frame: 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 Vz/F of teduglutide was reported. safety 15.Number of Participants With Treatment-Emergent Adverse | — |
Countries
Japan
Outcome results
None listed