Naloxegol Health Outcome Post Authorisation Safety Study

Study Overview
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Brief Summary
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This post-authorization observational safety study (PASS) monitors clinically important identified and potential risks within a cohort of patients treated with naloxegol, including the occurrence of bowel perforation, acute myocardial infarction (MI), stroke, cardiovascular (CV)-specific mortality, all-cause mortality, hypertension, opioid withdrawal, abdominal pain, diarrhea, syncope, and change in pain severity. This study is part of a broader post-marketing commitment to augment routine evaluation of the safety profile of naloxegol in clinical practice.

Detailed Description
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The overall research goal for this study is to provide additional data to characterize the safety of naloxegol in the indicated population, grouped by cancer or non-cancer, and within at-risk vulnerable non-cancer populations identified in the naloxegol risk management plan (RMP) by describing type and frequency of identified and potential risks (including bowel perforation, acute MI, stroke, CV-specific mortality, all-cause mortality, hypertension, opioid withdrawal, abdominal pain, diarrhea, syncope, and change in pain severity) in patients ≥18 years of age who were treated with opioids chronically and subsequently treated with naloxegol in routine post-authorization use. The primary objective of the study is to assess the incidence risk of bowel perforation, acute MI, stroke, all-cause mortality, and hypertension in patients treated with naloxegol (Naloxegol Inception Cohort, (NIC)), grouped by cancer or non cancer, a Concurrent Reference Cohort (CRC) by cancer or non-cancer, and by pre-specified non-cancer sub-populations that include patients aged ≥65 years, pregnant patients, patients with prior CV, patients with prior renal or hepatic impairment, patients with concurrent methadone use, and patients with concurrent use of cytochrome P450 (CYP) 3A inhibitors/inducer or P-glycoprotein (Pgp) modulators. An exploratory objective of the study is to assess the incidence risk of CV-specific mortality, opioid withdrawal, abdominal pain, diarrhea, syncope, and change in pain severity in patients treated with naloxegol (NIC) grouped by cancer and non cancer, a CRC grouped by cancer or non cancer, and by pre-specified non-cancer sub-populations that include patients aged ≥65 years, pregnant patients, patients with prior cardiovascular risk, patients with prior renal or hepatic impairment, patients with concurrent methadone use, and patients with concurrent use of CYP3A inhibitors/inducer or Pgp modulators.

Official Title
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An Observational Post-Authorisation Safety Study (PASS) of MOVENTIG® (Naloxegol) Among Patients Aged 18 Years and Older Treated With Opioids Chronically

Conditions
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Opioid Induced Constipation

Intervention / Treatment
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* Drug: naloxegol
* Drug: non-PAMORA laxative


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patient receives a new prescription for naloxegol or a non-PAMORA laxative. (Note: Only non-PAMORA laxatives that are approved/marketed in the European Union at the time naloxegol is authorized are permitted.) Exclusion Criteria: Patients <18 years of age on cohort entry date Patients with <1 year of continuous data available prior to cohort entry date Patients without exposure to current regular opioid use defined by >30 days of opioid exposure within the 180 days prior to and inclusive of the cohort entry date Patients with evidence of a cancer indicator (diagnosis or treatment) prior to cohort entry date Exposure to PAMORA laxatives, alvimopan, methylnaltrexone, or naloxone + opioid combination (including fixed-dose combinations) prior to cohort entry date
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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| naloxegol<br>patients exposed to naloxegol | Drug: naloxegol<br>* non-interventional study where patients are exposed to naloxegol during normal clinical practice<br>|
| non-PAMORA laxative<br>patient exposed to non-peripherally acting mu-opioid receptor antagonist (PAMORA) laxative | Drug: non-PAMORA laxative<br>* non-interventional study where patients are exposed to non-peripherally acting mu-opioid receptor antagonist (PAMORA) laxative<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence (yes/no) of bowel perforation |  | can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years | 
| Presence (yes/no) of acute MI |  | can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years | 
| Presence (yes/no) of stroke |  | can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years | 
| Presence (yes/no) of all-cause mortality |  | can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years | 
| Presence (yes/no) of hypertension |  | can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years |