An Observational Post-Authorization Safety Study (PASS) of MOVENTIG® (Naloxegol) Among Patients Aged 18 Years and Older Treated with Opioids Chronically

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Retrospective study

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  NALOXEGOL
• Medical condition to be studied:
  Large intestine perforation

  Small intestinal perforation

  Acute myocardial infarction

  Cerebral infarction

  Cerebellar infarction

  Cerebrovascular accident

  Cerebral haemorrhage

  Cerebellar haemorrhage

  Death

  Hypertension

Population studied

• Short description of the study population:
  The study focused on patients from the UK, Germany, and the Netherlands who receive naloxegol prescriptions. Patients aged 18 and above, with at least one year of continuous data, and exposure to regular opioid use, will be included in the National Institute of Addiction and Metabolism (NIC). Patients with non-PAMORA laxative prescriptions will be included in the Clinical Research Centre (CRC). Patients will be grouped by cancer or non-cancer for analysis.; 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 EU at the time naloxegol is authorised are permitted).; ; Patients will be excluded from either the NIC or CRC if they meet any of the following 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 (current regular opioid use defined by > 302 days of opioid exposure within the 180 days prior to and inclusive of the cohort entry date).; 4. Exposure to PAMORA laxatives, alvimopan, methylnaltrexone, or naloxone + opioid combination (including fixed-dose combinations) prior to cohort entry date.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  10000

Study design details

• Main study objective:
  To assess the incidence of bowel perforation, acute MI, stroke, all-cause mortality, and hypertension in patients treated with naloxegol, a concurrent reference cohort, and by subpopulations (patients aged ?65 years, or pregnant, or with prior cardiovascular risk, or with prior renal or hepatic impairment, or with concurrent methadone use or use of CYP3A inhibitors/inducers or PgP modulators)
• Outcomes:
  Bowel perforation, acute MI, stroke, all-cause mortality, and hypertension. CV-specific mortality, opioid withdrawal, abdominal pain, diarrhea, syncope, and change in pain severity
• Data analysis plan:
  Demographic, clinical, and treatment characteristics in the patients’ medical history for the naloxegol inception cohort and concurrent reference cohort overall and within sub-populations of interest are described. Incidence proportion and exposure-adjusted incidence rates for pre-specified health outcomes of interest, and their 95% confidence interval, are reported, by presence or absence of cancer. Incidence proportion is the number of patients with the outcome divided by the total number of patients. Exposure-adjusted incidence rate is the number of first occurrences of each health outcome divided by the total aggregate person-time accrued by all patients in that exposure group. The 95% CI were calculated based on the Wilson Score method. Sensitivity analyses were not conducted due to early termination of the study. Empirical time-to-event curves were derived for time to each of outcomes of interest. The Kaplan-Meier method was used to ascertain the shape of the distributions.

Documents

Study results

Naloxegol_SES_final report_2022_V1.0_Abstract