Naloxegol Health Outcome Post Authorisation Safety Study
- Conditions
- Opioid Induced Constipation
- Interventions
- Drug: non-PAMORA laxative
- Registration Number
- NCT02813369
- Lead Sponsor
- Kyowa Kirin Pharmaceutical Development Ltd
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 10000
- 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.)
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description non-PAMORA laxative non-PAMORA laxative patient exposed to non-peripherally acting mu-opioid receptor antagonist (PAMORA) laxative naloxegol naloxegol patients exposed to naloxegol
- Primary Outcome Measures
Name Time Method 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 of a diagnostic code for cerebral, cerebellar haemorrhage or infarction, cerebral embolism, stroke or cerebrovascular accident
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 of a diagnostic or procedure code
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 of a diagnostic code for acute MI, a diagnostic code for electrocardiogram supportive of MI or cardiac enzyme lab tests with positive results
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 Record of death
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 Presence of a hypertension (HT) diagnostic code where no record of HT or treatment for HT was observed in the baseline, or a record of change in HT treatment type or dose from baseline was observed.
- Secondary Outcome Measures
Name Time Method Presence of (yes/no) opioid withdrawal Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years Presence of a diagnosis or symptom code
Presence of (yes/no) diarrhea Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years Presence of a diagnosis or symptom code
Presence of (yes/no) CV-specific mortality Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years Record of death that indicates the cause was a CV event
Presence of (yes/no) abdominal pain Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years Presence of a diagnosis or symptom code
Presence of (yes/no) syncope Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years Presence of a diagnosis code
Presence of (yes/no) change in pain severity Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years At least a doubling in opioid dose based on the morphine milligram equivalents (MME) from baseline
Trial Locations
- Locations (1)
Research Site
🇬🇧Sutton, Surrey, United Kingdom