Tolerability, Safety, and Feasibility of Naloxegol in Patients With Cancer and OIC (Opioid Induced Constipation)

Exclusion Criteria

• •Cancer-related/medical comorbidity-related
• •* Patients with a past or current history of intra-abdominal neoplasm AND clinical findings that, on review by the investigator, may increase the risk of bowel perforation
• •* An active condition associated with clinically significant brain pathology, including known brain metastases, meningeal metastases, past traumatic brain injury, multiple sclerosis, uncontrolled epilepsy with signs or symptoms of compromised blood brain barrier
• •* Patients expected to undergo a first course of a chemotherapy regimen during the study period, patients who received a vinca alkaloid within 2 months, patients who have any history of vinca-associated GI autonomic neuropathy and/or constipation, or patients receiving a chemotherapy regimen including a VEGF-inhibitor (e.g., bevacizumab, sorafenib).
• •* Requiring radiation therapy between the diaphragm and pelvis 2 weeks prior to Visit 1 (screening) and/or during the study
• •* Any other significant and/or progressive condition (medical, neurological, psychiatric or metabolic) or symptom that could increase the risk of participation in the study or affect the interpretation of study data as determined by the investigator (e.g., uncontrolled hypothyroidism, inadequately controlled clinical depression, poorly controlled seizure disorder)
• •* Hemorrhagic diathesis
• •* Expected to have a surgical procedure requiring general anesthesia during the study period
• •Other gastrointestinal disorders
• •* Medical conditions and treatments, which in the judgment of the investigator, may be associated with diarrhea, intermittent loose stools, or constipation, (e.g., active diverticular disease, peritonitis of any cause, inflammatory bowel disease, active irritable bowel syndrome, chronic idiopathic constipation).
• •* Any conditions that could affect the absorption or metabolism of the study drug (e.g., malabsorption syndrome, severe liver disease) as judged by the investigator
• •* Evidence of fecal impaction either by physical or x-ray exam
• •* Known or suspected mechanical GI obstruction
• •* Current peritoneal catheter for intra-peritoneal chemotherapy or dialysis
• •* Fecal ostomy
• •* History of fecal incontinence
• •* History of bowel surgery within 60 days of the screening period
• •* Any other potential non-opioid cause of bowel dysfunction that in opinion of investigator might be a contributor to the constipation
• •Pain-related
• •* Receiving opioid medication on less than daily dosing schedule only
• •* Severe background pain (eg, typical average daily pain intensity rating of 8 to 10 on an 11-point NRS) refractory opioid therapy
• •Any of the following findings or conditions between the enrollment and randomization visits:
• •* Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 x upper limit normal (ULN) and/or serum bilirubin \>2 x ULN (unless elevation is due to Gilbert's syndrome)
• •* Calculated Creatinine clearance \<30 ml/min
• •* A Fridericia corrected QT interval (QTcF) \> 500 msec at screening, history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure despite treatment, unstable angina, or symptomatic peripheral vascular disease
• •* Active substance or alcohol use that, in the opinion of the investigator, may compromise patient's ability to comply with the study instructions
• •* Use of prohibited medications as listed in Section 5.5
• •* Pregnancy or lactation
• •* Known history of intolerance or hypersensitivity to alvimopan, methylnaltrexone, or other peripherally acting opioid antagonists or to any other component in the tablets
• •* Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff, staff at the study site, and third-party vendors)
• •* Any receipt of an investigational medication within 30 days of screening.