E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of short bowel syndrome dependent on parenteral support |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of short bowel syndrome dependent on parenteral support |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this clinical study was to evaluate the safety, tolerability, efficacy, pharmacodynamics, and pharmacokinetics of teduglutide in Japanese pediatric subjects (4 months through 15 years of age) with short bowel syndrome who were dependent on parenteral support. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed consent by a parent or guardian prior to any study-related procedures - When applicable, informed assent (as deemed appropriate by the Institutional Review Board) by the participant prior to any study-related procedures - Male or female infant 4 to <12 months corrected gestational age or child or adolescent aged 1 year through 15 years - Current history of SBS as a result of major intestinal resection (eg, due to necrotizing enterocolitis, midgut volvulus, intestinal atresia, or gastroschisis) - Short bowel syndrome that requires PN/IV support that provides at least 30% of caloric and/or fluid/electrolyte needs - Stable PN/IV support, defined as: -- For infants 4 to <12 months corrected gestational age: 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 1 month prior to and during screening, as assessed by the investigator. -- For children 1 to 15 years of age: 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 of sepsis is allowed if the PN/IV support returns to within 10% of baseline prior to the event. - Sexually active female participants of childbearing potential must use medically acceptable methods of birth control during and for 4 weeks following the last dose of investigational product. |
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E.4 | Principal exclusion criteria |
- Participants who are not expected to be able to advance oral or tube feeding regimens - Serial transverse enteroplasty or any other bowel lengthening procedure performed within 3 months of screening - Known clinically significant untreated intestinal obstruction contributing to feeding intolerance and inability to reduce parenteral support - Unstable absorption due to cystic fibrosis or other known DNA abnormalities (eg, Familial Adenomatous Polyposis, Fanconi-Bickel syndrome) - 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. - Evidence of clinically significant obstruction on the most recent upper GI series done within 6 months prior to screening. - Major GI surgical intervention including significant intestinal resection within 3 months prior to screening (insertion of feeding tube, anastomotic ulcer repair, minor intestinal resections <=10 centimeter (cm), or endoscopic procedure is allowed) - Unstable cardiac disease or congenital heart disease or cyanotic disease, with the exception of participants who had undergone ventricular or atrial septal defect repair, and patent ductus arteriosus (PDA) ligation - History of cancer or clinically significant lymphoproliferative disease, not including resected cutaneous basal or squamous cell carcinoma, or in situ nonaggressive and surgically resected cancer. Participants with known cancer predisposition syndrome, such as juvenile polyposis or Beckwith-Wiedemann syndrome, or first degree relative with early onset of GI cancer (including hepatobiliary and pancreatic cancer) will also be excluded. - Pregnant or lactating female participants - 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 - Previous use of teduglutide or native/synthetic GLP-2 - Previous use of glucagon-like peptide-1 analog or human growth hormone within 3 months prior to screening - Previous use of octreotide or dipeptidyl peptidase-4 (DPP-4) inhibitors within 3 months prior to screening - Participants 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 - Participants with inflammatory bowel disease (IBD) who require chronic systemic immunosuppressant therapy that had been introduced or changed during the 3 months prior to screening - More than 3 serious complications of SBS (eg, documented infection-related catheter sepsis, clots, bowel obstruction, severe water-electrolyte disturbances) within 3 months prior to the screening visit - A serious complication that affects parenteral support requirements within 1 month prior to or during screening, excluding uncomplicated treatment of bacteremia, central line replacement/repair, or issues of similar magnitude in an otherwise stable participant - Body weight < 5 kilogram (kg) at screening and baseline visits - Signs of active, severe, or unstable clinically significant hepatic impairment during the screening period - Signs of known continuous active or unstable, clinically significant renal dysfunction shown by results of an estimated glomerular filtration rate (eGFR) below 50 mL/min/1.73 m^2 - Unstable, clinically significant, active, untreated pancreatic or biliary disease
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in Parenteral Nutrition/Intravenous Fluids (PN/IV) Support - Change in Plasma Citrulline Levels - Change in Enteral Nutritional (EN) Support - Number of Participants With Adverse Events (AEs) - Change in Urine Output - Change in Fecal Output - Pharmacokinetics |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |