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

Study Overview
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Brief Summary
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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
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Subjects will be randomized according to an adaptive randomization procedure.

Official Title
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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

Conditions
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Postoperative Ileus

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative ileus, POI, major open abdominal surgery