Short Bowel Syndrome MedDRA version: 19.0 Level: PT Classification code 10049416 Term: Short-bowel syndrome System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Trade Name: Teduglutide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Teduglutide
CAS Number: 287714-30-1
Sponsors
NPS Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent by a parent or guardian or emancipated minor prior to any study-related procedures 2. When applicable, an informed assent by the subject (as deemed appropriate by the Ethics Committee/Institutional Review Board) prior to any study-related procedures 3. Current history of SBS as a result of major intestinal resection, (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis) 4. Short bowel syndrome that requires PN/IV support that provides at least 30% of caloric and/or fluid/electrolyte needs prior to screening 5. Stable PN/IV support, defined as inability to significantly reduce PN/IV support, usually associated with minimal or no advance in enteral feeds (ie, 10% or less change in PN or advance in feeds) for at least 3 months prior to and during screening, as assessed by the investigator. Transient instability for events such as interruption of central access or treatment for sepsis is allowed if the PN/IV support returns to within 10% of baseline prior to the event. 6. Sexually active female subjects of child-bearing potential (in the teduglutide treatment arm only) must use medically acceptable methods of birth control during and 4 weeks after the treatment period Are the trial subjects under 18? yes Number of subjects for this age range: 38 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects who are not expected to be able to advance oral or tube feeding regimens 2. Serial transverse enteroplasty or any other bowel lengthening procedure performed within 3 months of screening 3. Known clinically significant untreated intestinal obstruction contributing to feeding intolerance and inability to reduce parenteral support 4. Unstable absorption due to cystic fibrosis or known DNA abnormalities (eg, Familial Adenomatous Polyposis, Fanconi-Bickel syndrome) 5. Severe, known dysmotility syndrome, such as pseudo-obstruction or persistent, severe, active gastroschisis-related dysmotility, that is the primary contributing factor to feeding intolerance and inability to reduce parenteral support, prior to screening. Dysmotility is defined as severe if it is expected to limit the advancement of enteral feeding. 6. Evidence of clinically significant obstruction on upper gastrointestinal (GI) series done within 6 months prior to screening 7. Major GI surgical intervention including significant intestinal resection within 3 months prior to the screening visit (insertion of feeding tube, anastomotic ulcer repair, minor intestinal resections =10 cm, or endoscopic procedure is allowed) 8. Unstable cardiac disease, congenital heart disease or cyanotic disease, with the exception of subjects who had undergone ventricular or atrial septal defect repair, and patent ductus arteriosus (PDA) ligation 9. History of cancer or clinically significant lymphoproliferative disease, not including resected cutaneous basal or squamous cell carcinoma, or in situ non-aggressive and surgically resected cancer 10. Pregnant or lactating female subjects (in the teduglutide treatment arm only) 11. Participation in a clinical study using an experimental drug (other than glutamine or Omegaven) within 3 months or 5.5 half-lives of the experimental drug, whichever is longer, prior to screening and for the duration of the study 12. Previous use of teduglutide or native/synthetic glucagon-like peptide-2 (GLP-2) 13. Previous use of glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening 14. Previous use of octreotide or dipeptidyl peptidase-4 (DPP-4) inhibitors within 3 months prior to screening 15. Subjects with active Crohn's disease who had been treated with biological therapy (eg, antitumor necrosis factor [anti-TNF]) within the 6 months prior to the screening visit 16. Subjects with inflammatory bowel disease (IBD) who require chronic systemic immunosuppressant therapy that had been introduced or changed during the 3 months prior to screening 17. More than 3 SBS-related or PN-related hospital admissions (eg, documented infect
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this clinical study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy/pharmacodynamics of teduglutide in pediatric subjects (through 17 years) with SBS who are dependent on parenteral support.;Secondary Objective: Not applicable;Timepoint(s) of evaluation of this end point: 24 weeks or EoT; Primary end point(s): A 20% reduction or greater (including complete weaning) from baseline in volume of PN/IV at the end of 24 weeks of treatment The primary pharmacodynamic (PD) parameter is parenteral support reduction of 20% to 100% at 24 weeks (or EOT) compared to baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): provide further information on the safety, PK, and efficacy/PD profile of teduglutide in pediatric subjects treated for up to 24 weeks.; Timepoint(s) of evaluation of this end point: Additional PD endpoints include: ?100% reduction in PN/IV volume (complete weaning of PN/IV support) at week 24 (or EOT) compared to baseline ? Changes (absolute and percent change) from baseline in PN/IV support (volume and calories), citrulline and enteral nutritional support (volume and calories), separately, at each clinic visit ? Changes (absolute and percent change) from week 24 (or EOT) in PN/IV support (volume and calories), citrulline, and enteral nutritional support (volume and calories), separately, to week 28 (or EOS) ? Change in hours per day and days per week of PN/IV support ? =20% reduction in PN/IV volume at each clinic visit Pharmacokinetics: teduglutide treatment arm only blood collected on day 0 predose and 1, 2, and 4 hours postdose. | — |
Countries
Belgium, Canada, Finland, France, Germany, Italy, United Kingdom, United States
Contacts
Public ContactClinical Medical Monitor
Shire
Outcome results
None listed