Short Bowel Syndrome MedDRA version: 16.1 Level: PT Classification code 10049416 Term: Short-bowel syndrome System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: teduglutide for injection
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: Teduglutide
CAS Number: 197922-42-2
Other descriptive name: TEDUGL
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 prior to any study-related procedures (as deemed appropriate by the Ethics Committee/Institutional Review Board) 3. Current history of SBS as a result of major intestinal resection, (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis) for at least 12 months prior to screening 4. Short bowel syndrome that requires parenteral nutrition/intravenous (PN/IV) support that provides at least 30% of caloric and/or fluid/electrolyte needs 5. Stable PN/IV support for at least 3 months prior to enrollment based upon the opinion of the investigator and approval by the Sponsor’s Medical Monitor 6. Female subjects of child-bearing potential must use medically acceptable methods of birth control during and for 30 days after the treatment period. Are the trial subjects under 18? yes Number of subjects for this age range: 36 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. Serial transverse enteroplasty or any other bowel lengthening procedure performed within the past 3 months 2. Evidence of untreated intestinal obstruction or active stenosis 3. Unstable absorption due to cystic fibrosis, untreated Hirschsprung’s disease or known DNA abnormalities (ie, Familial Adenomatous Polyposis, Fanconi syndrome) 4. Radiographic or manometric evidence of pseudo-obstruction or severe known dysmotility syndrome, including gastroschisis-related motility disorders 5. Evidence of obstruction on upper gastrointestinal (GI) series done within 6 months prior to screening 6. Major gastrointestinal surgical intervention within 3 months prior to screening (insertion of feeding tube or endoscopic procedure is allowed) 7. Unstable cardiac disease, congenital heart disease or cyanotic disease, with the exception of subjects who had undergone ventricular or atrial septal defect repair 8. History of cancer or clinically significant lymphoproliferative disease within 5 years, not including resected cutaneous basal or squamous cell carcinoma, or in situ non-aggressive and surgically resected cancer 9. Pregnant or lactating female subjects 10. Participation in a clinical study using an experimental drug within 1 month or an experimental antibody treatment within 3 months prior to screening, or concurrent participation in any clinical study using an experimental drug that would affect the safety of teduglutide 11. Previous use of native glucagon-like peptide-2 (GLP-2) and glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening 12. Previous use of oral or IV glutamine, octreotide, or dipeptidyl peptidase IV (DPP-IV) inhibitors within 3 months prior to screening 13. Previous use of teduglutide 14. Subjects with active Crohn’s disease who had been treated with biological therapy (eg, antitumor necrosis factor [anti-TNF] or natalizumab) within the 6 months prior to screening 15. Subjects with inflammatory bowel disease (IBD) who required chronic systemic immunosuppressant therapy that had been introduced or changed during the last 3 months 16. More than 3 SBS-related or PN-related hospital admissions (eg, catheter sepsis, clots, bowel obstruction, severe water-electrolyte disturbances) within 3 months prior to screening visit 17. Hospital admission, other than scheduled, within 1 month prior to screening 18. Body weight < 5 percentile for age or < 10 kg 19. Signs of severe hepatic impairment: a. Total bilirubin = 2 x upper limit of normal (ULN) b. Aspartate aminotransferase (AST) = 5 x ULN c. Alanine aminotransferase (ALT) = 5 x ULN For subjects with Gilbert’s disease: d. Indirect (unconjugated) bilirubin = 2 x ULN 20. Signs of or disturbed renal function: a. Serum creatinine = 2 x ULN b. Creatinine clearance < 50 mL/min 21. Parent(s) and/or subjects who are not capable of understanding or not willing to adhere to the study visit schedule and other protocol requirements 22. Active or history of clinically significant pancreatic or biliary disease 23. Any condition or circumstance that in the investigator’s opinion puts the subject at any undue risk, prevented completion of the study, or interfered with analysis of the study results 24. Presence of any of the excluded disease states
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this clinical study is to evaluate the pharmacokinetic (PK) profile, safety and tolerability, and pharmacodynamic effects of teduglutide compared with standard of care in pediatric subjects (aged 1 year through 17 years) with short bowel syndrome (SBS) who are dependent on parenteral support.;Secondary Objective: Not applicable;Primary end point(s): Pharmacokinetic parameters: Study drug doses will be evaluated based on PK sampling and increased absorptive capacity as measured by PN/IV volume reduction. Samples for PK analysis will be collected pre-dose, at 1 and 6 hours post-dose at the start of treatment (SOT) and again at Week 4 predose, and 2 and 4 hours postdose for subjects in Cohorts 1, 2, and 3. If blood samples are not/cannot be collected at Week 4, the uncollected samples can be collected during any future visit while the subject is still on study drug. The following parameters will be derived: • Area under the plasma concentration–time curve (AUC) of zero to infinity (0–inf); • AUC from zero to the last measurable concentration (AUC0–t); • Maximum plasma concentration (Cmax); • Time to Cmax (tmax); • Terminal-phase half-life (t1/2?z); • Apparent clearance (CL/F); • Apparent volume of distribution (V?z/F) Safety and Tolerability Safety and tolerability will be assessed by evaluations of: • Adverse events, including GI symptoms • Vital signs, including changes in body weight • Electrocardiograms • Laboratory safety data, including electrolyte balance • Antibodies to teduglutide and Escherichia coli protein (ECP). Samples for antibody analysis will be drawn at SOT and at the end of treatment (EOT ) visit (prior to the administration of teduglutide and at least 14 hours after the previous dose). One sample will also be collected at the final visit 4 weeks after the EOT. It is planned to follow-up with any subjects testing positive for antibodies to teduglutide for up to 6 months after the last dose of study drug. • Maintaini | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Sweden, United Kingdom, United States
Contacts
Public ContactClinical Operations
NPS Pharmaceuticals, Inc.
Outcome results
None listed