Clinical trial NCT00617552: Safety and Efficacy of IV Infusion of TZP-101 for POI After Major Open Abdominal Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postoperative Ileus
Keywords: postoperative ileus
POI
major open abdominal surgery
Lead sponsor: Tranzyme, Inc.
Sponsor class: INDUSTRY
First posted: 2008-02-18
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: Subjects will be randomized according to an adaptive randomization procedure.

Eligibility criteria: 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

Primary outcomes:
measure: Time to recovery of gastrointestinal function as defined by the time to first bowel movement.
timeFrame: 7 days of dosing plus 7 days after administration of last dose
Secondary outcomes:
measure: time to tolerance of first solid food
timeFrame: 7 days post administration of last dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Office of Dr. Phillip Fleshner
state: California
city: Miami
country: United States
facility: University of Miami Clinic
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Univ. of Maryland, R.A. Cowley Shock Trauma Center
state: Maryland
city: Springfield
country: United States
facility: Baystate Medical Center/Baystate Health
state: Massachusetts
city: Grand Rapids
country: United States
facility: Michigan State/Spectrum Health
state: Michigan
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Bangalore
country: India
facility: St. John's Hospital
state: Karnataka
city: Chennai
country: India
facility: Stanley Medical College
city: Cochin
country: India
facility: Amrita Institute of Medical Sciences
city: Cochin
country: India
facility: Lakeshore Hospital
city: Hyderabad
country: India
facility: Asian Institute of Gastroenterology
city: Hyderabad
country: India
facility: Nizams Institute of Medical Science
city: Hyderabad
country: India
facility: Mediciti Hospitals
city: Lucknow
country: India
facility: Sanjay Gandhi Post-Graduate Institute of Medical Sciences
city: Bucharest
country: Romania
facility: Spitalul Urg. SF. Pantelimon
city: Bucharest
country: Romania
facility: Spitalul Universitar Elias
city: Bucuresti
country: Romania
facility: Clinica de Chirugie General IV, Spitalul Universitar
city: Bucuresti
country: Romania
facility: Clinica de Chirugie Generala I, Spitalul Universitar
city: Bucuresti
country: Romania
facility: Clinica de Chirugie Generala III, Spitalul Universitar
city: Bucuresti
country: Romania
facility: Institul Clinic Fundeni
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Bucuresti
country: Romania
facility: Spitalul Clinic Coltea
city: Bucuresti
country: Romania
facility: Spitalul Clinic de Urgenta Floreasca
Study officials:
References: