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

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

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).

Study Overview

• Status: Completed
• Conditions: Postoperative Ileus
• Intervention / Treatment: Drug: 5% dextrose in water; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101; Drug: TZP-101

Detailed Description

Subjects will be randomized according to an adaptive randomization procedure.

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Chennai, India, 600001
    • Stanley Medical College
  • Cochin, India, 682026
    • Amrita Institute of Medical Sciences
  • Cochin, India, 682304
    • Lakeshore Hospital
  • Hyderabad, India, 500082
    • Asian Institute of Gastroenterology
  • Hyderabad, India, 500083
    • Nizams Institute of Medical Science
  • Hyderabad, India, 50063
    • Mediciti Hospitals
  • Lucknow, India, 226014
    • Sanjay Gandhi Post-Graduate Institute of Medical Sciences
  • Karnataka
    • Bangalore, Karnataka, India
      • St. John's Hospital
• Romania
  • Bucharest, Romania, 021659 RO
    • Spitalul Urg. SF. Pantelimon
  • Bucharest, Romania
    • Spitalul Universitar Elias
  • Bucuresti, Romania, 00000 RO
    • Clinica de Chirugie General IV, Spitalul Universitar
  • Bucuresti, Romania, 00000 RO
    • Clinica de Chirugie Generala I, Spitalul Universitar
  • Bucuresti, Romania, 00000 RO
    • Clinica de Chirugie Generala III, Spitalul Universitar
  • Bucuresti, Romania, 00000 RO
    • Institul Clinic Fundeni
  • Bucuresti, Romania, 00000 RO
    • Spitalul Clinic Colentina
  • Bucuresti, Romania, 00000 RO
    • Spitalul Clinic Coltea
  • Bucuresti, Romania, 00000 RO
    • Spitalul Clinic de Urgenta Floreasca
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Office of Dr. Phillip Fleshner
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Clinic
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ. of Maryland, R.A. Cowley Shock Trauma Center
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center/Baystate Health
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Michigan State/Spectrum Health
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
  • Texas
    • Houston, Texas, United States, 77030
      • The Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Drug: TZP-101; 20 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 40 micrograms/kg IV 2 ml/minute for 30 minutes; Drug: TZP-101; 80 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 160 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 320 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 480 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 600 micrograms/kg IV 2ml/minute for 30 minutes
Placebo Comparator: 1	Drug: 5% dextrose in water; 60 ml IV infusion over 30 minutes; Other Names: D5W
Experimental: 3	Drug: TZP-101; 20 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 40 micrograms/kg IV 2 ml/minute for 30 minutes; Drug: TZP-101; 80 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 160 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 320 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 480 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 600 micrograms/kg IV 2ml/minute for 30 minutes
Experimental: 4	Drug: TZP-101; 20 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 40 micrograms/kg IV 2 ml/minute for 30 minutes; Drug: TZP-101; 80 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 160 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 320 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 480 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 600 micrograms/kg IV 2ml/minute for 30 minutes
Experimental: 5	Drug: TZP-101; 20 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 40 micrograms/kg IV 2 ml/minute for 30 minutes; Drug: TZP-101; 80 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 160 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 320 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 480 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 600 micrograms/kg IV 2ml/minute for 30 minutes
Experimental: 6	Drug: TZP-101; 20 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 40 micrograms/kg IV 2 ml/minute for 30 minutes; Drug: TZP-101; 80 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 160 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 320 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 480 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 600 micrograms/kg IV 2ml/minute for 30 minutes
Experimental: 7	Drug: TZP-101; 20 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 40 micrograms/kg IV 2 ml/minute for 30 minutes; Drug: TZP-101; 80 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 160 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 320 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 480 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 600 micrograms/kg IV 2ml/minute for 30 minutes
Experimental: 8	Drug: TZP-101; 20 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 40 micrograms/kg IV 2 ml/minute for 30 minutes; Drug: TZP-101; 80 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 160 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 320 micrograms/kg IV 2ml/minute for 30 minutes; Drug: TZP-101; 480 micrograms/kg IV 2ml/minute over 30 minutes; Drug: TZP-101; 600 micrograms/kg IV 2ml/minute for 30 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
time to tolerance of first solid food	7 days post administration of last dose

Collaborators and Investigators

• Sponsor: Tranzyme, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: February 6, 2008
• First Submitted That Met QC Criteria: February 6, 2008
• First Posted (Estimate): February 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 7, 2012
• Last Update Submitted That Met QC Criteria: December 5, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: postoperative ileus; POI; major open abdominal surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Ileus
• Other Study ID Numbers: TZP-101-CL-P005