Clinical trial NCT02813369: Naloxegol Health Outcome Post Authorisation Safety Study
Official title: An Observational Post-Authorisation Safety Study (PASS) of MOVENTIG® (Naloxegol) Among Patients Aged 18 Years and Older Treated With Opioids Chronically
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Opioid Induced Constipation
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-06-27
Enrollment: 10000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients in the targeted European countries who receive prescriptions for naloxegol will be identified for inclusion in the naloxegol inception cohort, while patients in these countries who receive a prescription for a non-PAMORA laxative will be identified for inclusion in the concurrent reference cohort. All patients in this study will be ≥18 years of age; have ≥1 year of continuous data available; have exposure to current, regular opioid use; and have no prior exposure to PAMORA laxatives alvimopan, methylnaltrexone, or naloxone + opioid combination (including fixed-dose combinations).

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.

Eligibility criteria: 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:

1. Patients \<18 years of age on cohort entry date
2. Patients with \<1 year of continuous data available prior to cohort entry date
3. 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
4. Patients with evidence of a cancer indicator (diagnosis or treatment) prior to cohort entry date
5. Exposure to PAMORA laxatives, alvimopan, methylnaltrexone, or naloxone + opioid combination (including fixed-dose combinations) prior to cohort entry date

Primary outcomes:
measure: Presence (yes/no) of bowel perforation
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence (yes/no) of acute MI
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence (yes/no) of stroke
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence (yes/no) of all-cause mortality
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence (yes/no) of hypertension
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
Secondary outcomes:
measure: Presence of (yes/no) CV-specific mortality
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence of (yes/no) opioid withdrawal
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence of (yes/no) abdominal pain
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence of (yes/no) diarrhea
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence of (yes/no) syncope
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Presence of (yes/no) change in pain severity
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
Other outcomes:
measure: Demographic characteristics
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Time characteristics
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Opioid-induced Constipation Characteristics: Prior constipation diagnosis
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Opioid-induced Constipation Characteristics: Type of prior opioid use
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Opioid-induced Constipation Characteristics: Amount of prior opioid use per day
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Opioid-induced Constipation Characteristics: The amount of opioid exposure within 180 days
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Opioid-induced Constipation Characteristics: Type of laxative use
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Opioid-induced Constipation Characteristics: Strength of laxative use
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Opioid-induced Constipation Characteristics: Pre-existing conditions and comorbidities
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Evaluation of patients biochemical measurements at baseline
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Healthcare resource utilization during 12 month baseline period prior to index date
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: History of GI surgery
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
measure: Exposure
timeFrame: Exposure to naloxegol or the concurrent reference laxative started on the index date. The exposure end date was calculated by an algorithm used to derive continuous exposure
measure: Prior and Concomitant Medications at Baseline
timeFrame: Can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 7 years
Locations:
city: Utrecht
country: Netherlands
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
state: Surrey
Study officials:
References: