Safety and Efficacy of IV Infusion of TZP-101 for POI After Major Open Abdominal Surgery

Postoperative Ileus Clinical Trial

Official title:

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess Efficacy and Safety of TZP-101 When Administered as 30 Minute i.v. Infusion for POI to Subjects Undergoing Major Open Abdominal Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00617552
• Other study ID #: TZP-101-CL-P005
• Status: Completed
• Phase: Phase 2
• First received: February 6, 2008
• Last updated: December 5, 2012
• Start date: July 2007
• Est. completion date: August 2008

Study information

• Verified date: December 2012
• Source: Tranzyme, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRomania: National Medicines AgencyLithuania: State Medicine Control Agency - Ministry of HealthIndia: Drugs Controller General of India
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether TZP-101 is effective in the management of post operative ileus in subjects undergoing major open abdominal surgery (i.e. partial large bowel resection).

Description:

Subjects will be randomized according to an adaptive randomization procedure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: August 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

Subjects who meet all of the following inclusion criteria may be enrolled in the study:

• Male or Female, 18 to 80 years of age, inclusive

• If female, post-menopausal for the past 12 months, surgically sterile (i.e. tubal ligation, hysterectomy), or using an adequate method of birth control (i.e., oral contraceptives, double barrier method, IUD cover or sterilized partner

• Subject is scheduled to undergo a partial large bowel resection with primary anastomosis - See Appendix II

• Subject's body weight is =100kg

• Subject is scheduled to receive postoperative pain management with i.v. opioids

• Subject is scheduled to have nasogastric tube removed at the end of surgery

• Subject is scheduled to be offered liquids on postoperative day 1

• Subject is scheduled to be encouraged for ambulation on postoperative day 1

• Subject is scheduled to be offered solid food on postoperative day 2

Exclusion Criteria:

Subjects who meet any of the following exclusion criteria may not be enrolled in the study:

• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450(men)/ >470(women) milliseconds)

• Subject has history of additional risk factors for Torsades de Pointes (heart failure, hypokalemia, family history of Long QT Syndrome)

• Subject requires use of concomitant medication that prolongs the QT interval - List provided in Study Procedures Manual

• Subject requires use of concomitant medication that is a known to interact with isoenzyme CYP3A4

• Subject has complete bowel obstruction

• Subject is scheduled to receive a thoracic epidural

• Subject is scheduled to receive total colectomy, colostomy, or ileostomy

• Subject is scheduled to receive a lower anterior resection

• Subject is scheduled for laparoscopic procedure

• Subject is scheduled to receive prophylactic antiemetics post surgery; however subjects may receive intraoperatively as part of the anesthesia protocol and postoperative antiemetics for symptomatic treatment

• Subject has significant impairment of liver or renal function (ALT/AST 2 ½ times the upper limit of normal; creatinine clearance < 50mL/min.)

• Subject has a psychiatric disorder or cognitive impairment that would interfere with participation in the study

• Subject has severe cardiovascular, pulmonary, hematological diseases

• Subject has participated in an investigational study 30 days prior or received TZP-101 90 days prior to the study initiation

• Subject is pregnant (confirmed by quantitative serum pregnancy test) or is breast-feeding

• Subject has a known history of Hep B, Hep C or HIV

• Subject has a known history of drug or alcohol abuse

• Subject has a recent, adult history of clinically significant hypersensitivity reaction(s) to any drug

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Postoperative Ileus

Intervention

Drug:
• 5% dextrose in water
60 ml IV infusion over 30 minutes
• TZP-101
20 micrograms/kg IV 2ml/minute for 30 minutes
• TZP-101
40 micrograms/kg IV 2 ml/minute for 30 minutes
• TZP-101
80 micrograms/kg IV 2ml/minute for 30 minutes
• TZP-101
160 micrograms/kg IV 2ml/minute over 30 minutes
• TZP-101
320 micrograms/kg IV 2ml/minute for 30 minutes
• TZP-101
480 micrograms/kg IV 2ml/minute over 30 minutes
• TZP-101
600 micrograms/kg IV 2ml/minute for 30 minutes

Locations

Country	Name	City	State
India	St. John's Hospital	Bangalore	Karnataka
India	Stanley Medical College	Chennai
India	Amrita Institute of Medical Sciences	Cochin
India	Lakeshore Hospital	Cochin
India	Asian Institute of Gastroenterology	Hyderabad
India	Mediciti Hospitals	Hyderabad
India	Nizams Institute of Medical Science	Hyderabad
India	Sanjay Gandhi Post-Graduate Institute of Medical Sciences	Lucknow
Romania	Spitalul Universitar Elias	Bucharest
Romania	Spitalul Urg. SF. Pantelimon	Bucharest
Romania	Clinica de Chirugie General IV, Spitalul Universitar	Bucuresti
Romania	Clinica de Chirugie Generala I, Spitalul Universitar	Bucuresti
Romania	Clinica de Chirugie Generala III, Spitalul Universitar	Bucuresti
Romania	Institul Clinic Fundeni	Bucuresti
Romania	Spitalul Clinic Colentina	Bucuresti
Romania	Spitalul Clinic Coltea	Bucuresti
Romania	Spitalul Clinic de Urgenta Floreasca	Bucuresti
United States	Univ. of Maryland, R.A. Cowley Shock Trauma Center	Baltimore	Maryland
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	Northwestern University	Chicago	Illinois
United States	Michigan State/Spectrum Health	Grand Rapids	Michigan
United States	The Methodist Hospital	Houston	Texas
United States	Office of Dr. Phillip Fleshner	Los Angeles	California
United States	University of Miami Clinic	Miami	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	Baystate Medical Center/Baystate Health	Springfield	Massachusetts
United States	Stony Brook University Hospital	Stony Brook	New York

Sponsors (1)

Lead Sponsor	Collaborator
Tranzyme, Inc.

Countries where clinical trial is conducted

United States,  India,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to recovery of gastrointestinal function as defined by the time to first bowel movement.		7 days of dosing plus 7 days after administration of last dose	No
Secondary	time to tolerance of first solid food		7 days post administration of last dose	No