Clinical trial NCT00798967: Study of Teduglutide Effectiveness in Parenteral Nutrition (PN)-Dependent Short Bowel Syndrome (SBS) Subjects
Official title: A 24-Week Study of the Efficacy and Safety of Teduglutide in Subjects With Parenteral Nutrition-Dependent Short Bowel Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Short Bowel Syndrome
Keywords: SBS
short bowel syndrome
TPN
parenteral nutrition
PN
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Nycomed
First posted: 2008-11-27
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Teduglutide is an investigative medicine being evaluated as a possible treatment for people with parenteral nutrition (PN) dependent Short Bowel Syndrome (SBS). Teduglutide is similar to a protein the body makes. When people have SBS, their bodies do not make enough of the protein and they have trouble getting nutrients and fluids from the food they eat and drink. This study was designed to provide evidence of efficacy, safety, and tolerability of teduglutide 0.05 mg/kg daily in SBS subjects.


Eligibility criteria: Inclusion Criteria:

* Signed and dated informed consent prior to any study-related procedures are performed
* Men and women 18 years of age or older at the time of informed consent signing
* Intestinal failure resulting in Short Bowel Syndrome
* At least 12 months of continuous PN dependency
* 12 weeks of clinical remission of Crohn's disease (CD) prior to dosing
* PN required at least 3 times weekly
* A stable PN volume for four weeks prior to dosing

Exclusion Criteria:

* History of cancer or clinically significant lymphoproliferative disease with fewer than 5 years documented disease-free state
* Participation in clinical study within 30 days for drug or 90 days for antibody
* Use of native GLP-2 or human growth hormone (HGH) within 6 months of screening
* Use of iv glutamine within 30 days prior to screening
* Use of teduglutide
* CD patients who have been treated with biological therapy within 6 months of screening
* IBD patients who require chronic systemic immunosuppressant therapy
* More than 4 SBS- or PN-related hospitalizations within 12 months of screening
* Unplanned hospitalization within one month of screening
* Pregnant or lactating women
* Body weight \> 88kg
* Body mass index (BMI) \< 15 kg/m2
* Severe hepatic impairment or disturbed renal function
* Female subjects who are not surgically sterile or postmenopausal or who are not using medically acceptable methods of birth control during and for 30 days after the treatment period
* Not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements
* Any condition or circumstance that is the investigator's opinion would put the subject at any undue risk, prevent completion of the study, or interfere with the analysis of the study results
* Significant active, uncontrolled, untreated systemic diseases

Primary outcomes:
measure: Responder
timeFrame: Weeks 20 and 24
Secondary outcomes:
measure: Absolute Change in PN/I.V. Volume From Baseline to Last Time Point
timeFrame: Week 0 to last visit when data was collected.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic & Research Foundation
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennslyvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Edmonton
country: Canada
facility: Critical Care Research, Royal Alexandra Hospital
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: North York
country: Canada
facility: Polyclinic Family and Specialty Medicine Facility
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto General Hospital
state: Ontario
city: København
country: Denmark
facility: Rigshospitalet - Abdominalcentret, Hepatologisk Kilinik A
city: Clichy
country: France
facility: Hôpital Beaujon
city: Lyon
country: France
facility: Hôpital Croix Rousse Unité de Nutrition Clinique Intensive
city: Nice Cedex 3
country: France
facility: Hôpital de l'Archet Pôle Digestif
city: Berlin
country: Germany
facility: Med. Klinik m.S. Hepatologie und Gastroenterologie
state: BE
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: BW
city: Hamburg
country: Germany
facility: Israelitisches Krankenhaus
state: HH
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria S. Giovanni Battista - Le Molinette
state: TO
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola - Malpighi centro insufficienza intestinale
city: Napoli
country: Italy
facility: Azienda Universitaria Policlinico Federico II
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Pirogowa, Pracownia Leczenia Zywieniowego
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4, Klinika Chirurgii Ogolnej i Transplantacyjnej
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny,
city: Warsaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny im. prof W. Orlowskiego CMKP, Oddzial Kliniczny Zywienia i Chirurgii
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Harrow
country: United Kingdom
facility: St. Mark's Hospital Northwick Park
state: Gt Lon
city: London
country: United Kingdom
facility: University College Hospital
state: Gt Lon
city: Manchester
country: United Kingdom
facility: Green Area, Main Hospital Salford Royal Hospitals NHS Foundation Trust
state: Gt Man
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Jeppesen PB, Sanguinetti EL, Buchman A, Howard L, Scolapio JS, Ziegler TR, Gregory J, Tappenden KA, Holst J, Mortensen PB. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients. Gut. 2005 Sep;54(9):1224-31. doi: 10.1136/gut.2004.061440.
citation: Jeppesen PB, Gabe SM, Seidner DL, Lee HM, Olivier C. Citrulline correlations in short bowel syndrome-intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study. Clin Nutr. 2020 Aug;39(8):2479-2486. doi: 10.1016/j.clnu.2019.11.001. Epub 2019 Nov 9.
citation: Jeppesen PB, Gabe SM, Seidner DL, Lee HM, Olivier C. Factors Associated With Response to Teduglutide in Patients With Short-Bowel Syndrome and Intestinal Failure. Gastroenterology. 2018 Mar;154(4):874-885. doi: 10.1053/j.gastro.2017.11.023. Epub 2017 Nov 22.
citation: Fujioka K, Jeejeebhoy K, Pape UF, Li B, Youssef NN, Schneider SM. Patients With Short Bowel on Narcotics During 2 Randomized Trials Have Abdominal Complaints Independent of Teduglutide. JPEN J Parenter Enteral Nutr. 2017 Nov;41(8):1419-1422. doi: 10.1177/0148607116663481. Epub 2016 Aug 9.
citation: Vipperla K, O'Keefe SJ. Study of teduglutide effectiveness in parenteral nutrition-dependent short-bowel syndrome subjects. Expert Rev Gastroenterol Hepatol. 2013 Nov;7(8):683-7. doi: 10.1586/17474124.2013.842894. Epub 2013 Oct 17.
citation: Jeppesen PB, Pertkiewicz M, Forbes A, Pironi L, Gabe SM, Joly F, Messing B, Loth S, Youssef NN, Heinze H, Berghofer P. Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study. Clin Nutr. 2013 Oct;32(5):713-21. doi: 10.1016/j.clnu.2013.03.016. Epub 2013 Mar 28.
citation: Berghofer P, Fragkos KC, Baxter JP, Forbes A, Joly F, Heinze H, Loth S, Pertkiewicz M, Messing B, Jeppesen PB. Development and validation of the disease-specific Short Bowel Syndrome-Quality of Life (SBS-QoL) scale. Clin Nutr. 2013 Oct;32(5):789-96. doi: 10.1016/j.clnu.2012.12.001. Epub 2012 Dec 12.
citation: Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O'keefe SJ, Forbes A, Heinze H, Joelsson B. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012 Dec;143(6):1473-1481.e3. doi: 10.1053/j.gastro.2012.09.007. Epub 2012 Sep 11.