post-operative ileus in subjects who have undergone partial bowel resection MedDRA version: 14.0 Level: PT Classification code 10054048 Term: Postoperative ileus System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Product Name: TZP-101 (ulimorelin) concentrate for solution for infusion
Product Code: TZP-101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ulimorelin hydrocholoride
Sponsors
Tranzyme, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following inclusion criteria may be enrolled in the study: • Subject is 18 to 80 years of age, inclusive. • Subject is scheduled to undergo open bowel resection with colonic anastomosis. • Subject is scheduled to receive post-operative pain management with parenteral opioids (eg, administered IV or IM), but not via thoracic epidural. • Subject is scheduled for the following Enhanced Recovery After Surgery (ERAS) measures: o Nasogastric (NG) tube removed at the end of surgery/anesthesia o Liquids offered on post-operative day 1 (dosing day 2) o Solid food offered on post-operative day 2 (dosing day 3) o Ambulation encouraged on post-operative day 1 (dosing day 2) • Female subjects must be postmenopausal (for at least 1 year and confirmed by serum follicle-stimulating hormone [FSH]), surgically sterile, practicing true sexual abstinence, OR must be using adequate contraception (in the opinion of the investigator) for the duration of the study including the follow-up period (eg, contraceptive implants, injectables, oral contraceptives, some intrauterine devices [IUD], and/or barrier method (condom or occlusive cap) with spermicidal foam/gel/film/cream/suppository). • Hormonal and IUD methods of contraception must be established for a period of 3 months prior to dosing, and if changed, alternative methods should be used as directed by the investigator throughout the duration of the study. • Females of childbearing potential must have a negative pregnancy test at screening and admission (human chorionic gonadotropin [beta- hCG]). After surgery and prior to administration of the first dose of study drug, the following eligibility criteria must be assessed: Inclusion: • Subject underwent open bowel resection with colonic anastomosis Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 235 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: • Subject weighs more than 200kg (441 pounds). • Subject is classified as American Society of Anesthesiologists (ASA) Class 4, 5, or 6 (See Section 11.2). • Subject has complete bowel obstruction. • Subject is scheduled to receive total colectomy. • Subject is scheduled to receive a low rectal or an anal anastomosis (eg, proctectomy, ileoanal anastomosis • Subject is scheduled to receive a stoma (eg, ileostomy, jejunostomy colostomy). • Subject is scheduled for laparoscopic or laparoscopic hand-assisted procedure. • Subject is scheduled to receive prophylactic anti-emetics post surgery; however subjects may receive intraoperative anti-emetics as part of the anesthesia protocol. • Subject is scheduled to receive a thoracic epidural for anesthesia or analgesia. • Subject’s surgical procedure is considered to be an emergency procedure. • Subject is scheduled to receive ENTEREG®/alvimopam or any other peripheral opioid antagonist such as RELISTOR®/methylnaltrexone bromide. • Subject has significant impairment of liver or renal function (alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) 2.5 times the upper limit of normal; creatinine clearance 450ms for males and QTc > 470ms for females at screening. • Subjects with clinically significant bradycardia or hypotension as judged by the investigator. • Subject is anticipated to require prolonged post-operative ventilation. • Subject has a psychiatric disorder or cognitive impairment that, in the opinion of the Investigator, would interfere with participation in the study. • Subject has participated in an investigational study 30 days prior to the study initiation • Subject has a positive laboratory test result for controlled substances (other than for those prescribed by a medical professional and/or accounted for by concomitant medications) at screening. • Subject is known to have Hepatitis B or Hepatitis C infection currently associated with clinically significant symptoms or abnormal liver function. • Subject has a recent, adult history of clinically significant hypersensitivity reaction(s) to any drug, in the opinion of the Investigator. • Subject is pregnant (confirmed by serum pregnancy test) or is breastfeeding. • Subject has known history of drug or alcohol abuse within the previous year. After surgery and prior to administration of the first dose of study drug, the following eligibility criteria must be assessed: Exclusion: • Subject has complete bowel obstruction. • Subject received a total colectomy. • Subject received a low rectal or anal anastomosis (eg, proctectomy or ileoanal anastomosis). • Subject received a stoma (eg, jejunostomy, ileostomy, colostomy). • Subject underwent a laparoscopic procedure (including a hand-assisted laparoscopic procedure). • Subject received a thoracic epidural for anesthesia or analgesia. • Subjects with clinically significant ECG findings, bradycardia or hypotension as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy and safety of 2 doses of IV ulimorelin in comparison to placebo administered post-operatively to accelerate recovery of GI motility in subjects who have undergone partial bowel resection, thereby reducing the duration of post-operative ileus (POI);Secondary Objective: No secondary objectives;Primary end point(s): The primary endpoint is the time to recovery of GI function as defined by the time from the end of surgery to GI2, the later of first BM and tolerance of solid food (ie, having finished a meal that required chewing and having experienced no significant nausea/vomiting for 4hr after the meal).;Timepoint(s) of evaluation of this end point: The time to reach GI2 is the primary endpoint. There will be a twice-daily review of clinical milestones (including primary endpoint) until discharge. Daily infusions of ulimorelin will continue until one of the following occurs: 1. GI2 (the later of first BM and tolerance of solid food). 2. Hospital discharge. 3. 7 days of treatment with study drug. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time from the end of surgery to first BM • GI2 by 72hr post surgery with no AE of “ileus*”, as defined per protocol, during the index admission, ie, the original admission for surgery (“responder” endpoint) • Time to “met discharge criteria” defined as meeting all of the following criteria: effective transit of intestinal contents (ie, had BM or flatus); tolerance of oral intake (ie, tolerance of 2 solid meals); analgesia consistent with discharge status (eg, adequate oral analgesia) and medically stable for discharge (eg, hospitalization is not required for treatment of a medical condition such as pneumonia, sepsis etc.) • GI2 by 72hr post surgery • Vomiting reported as an AE • Nausea reported as an AE • Ileus* reported as an AE • Time to “Discharge Order Written” • NG tube reinsertion • Failure to reach GI2 by end of Day 5 (120hr post surgery) • Time to discharge from the hospital * For the purposes of this study, any AE of “ ileus”(including “prolonged” and “paralytic” ileus etc.) needs to meet the following definition: NG tube reinsertion and/or “down-grading” of permitted oral intake to “NPO” (nothing by mouth), unless bowel obstruction is identified radiologically or at subsequent surgery.;Timepoint(s) of evaluation of this end point: There will be a twice-daily review of clinical milestones (including primary endpoint) until discharge | — |
Countries
Bulgaria, Czech Republic, France, Germany, Hungary, Lithuania, Spain, United States
Contacts
Public ContactClinical Trial Manager
Norgine Ltd
Outcome results
None listed