Opioid Induced ConstipationNCT02813356
Naloxegol US PMR CV Safety.
An observational study of Opioid Induced Constipation, run by Valinor Pharma LLC at 2 sites in United States.
Trial summary
The overall research goal for this study is to provide additional data to characterize the safety of naloxegol in patients aged 18 years and older who do not have a diagnosis of cancer and who are treated with opioids chronically Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Opioid Induced Constipation
- What is being tested?
- naloxegol and non-PAMORA
- How many people
- 8,800 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Jun 2016to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All patients in this study will be 18 years of age or older, and they will have had at least 6 months of continuous data available before they enter one of the new-user cohorts. During the 6-month baseline period before cohort entry, they will have received at least 90 days of dispensed opioids, of which in the 60 days before cohort entry there were at least 30 days of opioids dispensed at an average of at least 30 morphine equivalent units (MEQ) per day. Patients will have no evidence of active cancer; they will have no evidence in the electronic record of MACE; they will not have received methylnatrexone bromide for subcutaneous injection. At the time of the index dispensing of naloxegol or comparison drug, cohort members will furthermore be current users of a dispensed opioid.
Who may be able to join
- Patient receives a new dispensing of naloxegol, lubiprostone/linaclotide, or an oral NNPAMORA. A new dispensing is one that occurs with no dispensing for the same drug having occurred in the preceding 182 days. A patient only qualifies once under this criterion for any drug.
- Patients 18 years of age or older at the index date
- Continuous availability of data for at least 183 days immediately before and including the index date
- 90 days of opioid dispensed in the 183 days before and including the index date of which at least 30 days of opioid dispensed at at least 30 MEQ/day in the 60 days before and including index date
- Current users of a dispensed opioid, meaning that the interval between index study drug dispensing and at least 1 prior opioid dispensing is less than the days supply associated with the opioid dispensing
Who cannot join
- Any medical care associated with a diagnosis of cancer in the 183 days before and including the index date; a diagnosis of cancer for this purpose is any diagnostic code of International Classification of Diseases, 9th revision (ICD-9) in the range 140-208 "Malignant neoplasms …" or of the 10th revision (ICD-10) in the range C00-C96, "Malignant neoplasms"
- Dispensing of methylnaltrexone for subcutaneous injection in the 183 days before and including the index date
- Indication in the electronic records of the occurrence of MACE in the 183 days before and including the index date; see Section 9.3.2 "MACE" for screening criteria
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Research Site
Hines, Illinois, 60141
Research Site
Wilmington, Delaware, 19803
About this study
Official title: United States Post-Marketing Observational Cardiovascular Safety Study in Patients Taking Naloxegol
The overall research goal for this study is to provide additional data to characterize the safety of naloxegol in patients aged 18 years and older who do not have a diagnosis of cancer and who are treated with opioids chronically
Read the detailed description
The primary objective is to assess the overall risk of major adverse cardiovascular events (MACE) among naloxegol-treated patients compared to that among patients on prescription non-peripherally acting mu-opioid antagonist (PAMORA) opioid induced constipation (OIC) treatment. The corresponding analysis is of a new-user cohort study that captures the occurrence of MACE in persons receiving naloxegol or comparison medications. The study takes place in actual-use settings in the US in which existing electronic data captures patient diagnoses, health care, and treatment. The occurrence of MACE in naloxegol-treated patients will be compared to the occurrence of MACE in medically-similar new users of other prescription-only treatments for OIC in the same settings, with both naloxegol-treated and comparison medication-treated patients being followed for as long as they continue on therapy.
In further pursuit of the primary objective, there will be a self-controlled study that follows all members of the new-user cohorts, including both new naloxegol users and new users of comparator products, for as long as data are available as the patients may go on or off treatment. A self-controlled study offers a complementary approach to the statistical control for the possible confounding effects of personal characteristics. Using the same data sources, this self-controlled design follows individuals from the time they finish their first course of treatment as new users for as long as the study continues. Patient treatment statuses are continuously updated since the treatment choices exercised by patients and their caregivers create extended periods of study time on and off naloxegol and possibly on and off other therapies for OIC. Comparisons of the occurrence of MACE occur within individuals and so are unaffected by differences between individuals, as in a crossover trial.
The first secondary objective is to assess the potential confounding effects of lifestyle risk factors on relative risk of MACE among naloxegol-treated patients compared with that among patients on other prescription non-PAMORA OIC treatment. The corresponding analysis is of a case-control study nested within the primary study population. All of the MACE "cases" will be matched to other members of the cohorts ("controls"). In cases and controls, the outpatient medical record will be abstracted for information on lifestyle risk factors. The case-control analysis will provide information on the presence and effect of lifestyle confounding factors that may be identifiable only by chart review.
Further secondary analyses will investigate the relative risks analyzed under an intent-to-treat paradigm over fixed time periods of membership in the naloxegol and comparator cohorts, relative risks for specific components of MACE, relative risks associated with new oral PAMORA agents other than naloxegol (non-naloxegol oral PAMORAs [NNPAMORAs]) that may come onto the US market during the course of the study, and an exploration of the possible variations in risk associated with variations in the dose and timing of naloxegol dispensing in the case-control study.
- Conditions
- Opioid Induced Constipation
- Being tested
- naloxegol, non-PAMORA
- Medical subject headings
- Opioid-Induced Constipation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
naloxegolDrug
non-interventional study where naloxegol is prescribed during normal clinical practice
non-PAMORADrug
non-interventional study where patients are exposed to non-peripherally acting mu-opioid antagonists during the normal course of clinical practice
| Study group | Role | What they receive |
|---|---|---|
| naloxegol | patients exposed to naloxegol Receives: Drug: naloxegol | |
| non-PAMORA | patients exposed to non-peripherally acting mu-opioid antagonist Receives: Drug: non-PAMORA |
What is being measured
The primary outcome is the main question the study is designed to answer.
major adverse cardiovascular events
while exposed to naloxegol or comparator exposure, composite of major adverse cardiovascular events which includes cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke
Measured: can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2016 (estimated)
- Study start24 Jun 2016
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Induced ConstipationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 8,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Valinor Pharma LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Beth Nordstrom, Principal investigator, Evidera
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02813356
- Sponsor's protocol ID
- D3820R00008
- Other IDs
- EUPAS18201
- Status last verified
- May 2023
- First submitted
- 7 Jun 2016
- Last updated
- 15 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- United States Post-Marketing Observational Cardiovascular Safety Study in Patients Taking Naloxegol
- ClinicalTrials.gov ID
- NCT02813356
- Acronym / sponsor ID
- D3820R00008
- Conditions
- Opioid Induced Constipation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 8,800 participants (estimated)
- Lead sponsor
- Valinor Pharma LLCIndustry (pharma, biotech, devices)
- Study start
- 24 Jun 2016 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 27 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall research goal for this study is to provide additional data to characterize the safety of naloxegol in patients aged 18 years and older who do not have a diagnosis of cancer and who are treated with opioids chronically
Detailed description
The primary objective is to assess the overall risk of major adverse cardiovascular events (MACE) among naloxegol-treated patients compared to that among patients on prescription non-peripherally acting mu-opioid antagonist (PAMORA) opioid induced constipation (OIC) treatment. The corresponding analysis is of a new-user cohort study that captures the occurrence of MACE in persons receiving naloxegol or comparison medications. The study takes place in actual-use settings in the US in which existing electronic data captures patient diagnoses, health care, and treatment. The occurrence of MACE in naloxegol-treated patients will be compared to the occurrence of MACE in medically-similar new users of other prescription-only treatments for OIC in the same settings, with both naloxegol-treated and comparison medication-treated patients being followed for as long as they continue on therapy.
In further pursuit of the primary objective, there will be a self-controlled study that follows all members of the new-user cohorts, including both new naloxegol users and new users of comparator products, for as long as data are available as the patients may go on or off treatment. A self-controlled study offers a complementary approach to the statistical control for the possible confounding effects of personal characteristics. Using the same data sources, this self-controlled design follows individuals from the time they finish their first course of treatment as new users for as long as the study continues. Patient treatment statuses are continuously updated since the treatment choices exercised by patients and their caregivers create extended periods of study time on and off naloxegol and possibly on and off other therapies for OIC. Comparisons of the occurrence of MACE occur within individuals and so are unaffected by differences between individuals, as in a crossover trial.
The first secondary objective is to assess the potential confounding effects of lifestyle risk factors on relative risk of MACE among naloxegol-treated patients compared with that among patients on other prescription non-PAMORA OIC treatment. The corresponding analysis is of a case-control study nested within the primary study population. All of the MACE "cases" will be matched to other members of the cohorts ("controls"). In cases and controls, the outpatient medical record will be abstracted for information on lifestyle risk factors. The case-control analysis will provide information on the presence and effect of lifestyle confounding factors that may be identifiable only by chart review.
Further secondary analyses will investigate the relative risks analyzed under an intent-to-treat paradigm over fixed time periods of membership in the naloxegol and comparator cohorts, relative risks for specific components of MACE, relative risks associated with new oral PAMORA agents other than naloxegol (non-naloxegol oral PAMORAs [NNPAMORAs]) that may come onto the US market during the course of the study, and an exploration of the possible variations in risk associated with variations in the dose and timing of naloxegol dispensing in the case-control study.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| naloxegol | – | Drug: naloxegolpatients exposed to naloxegol |
| non-PAMORA | – | Drug: non-PAMORApatients exposed to non-peripherally acting mu-opioid antagonist |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients in this study will be 18 years of age or older, and they will have had at least 6 months of continuous data available before they enter one of the new-user cohorts. During the 6-month baseline period before cohort entry, they will have received at least 90 days of dispensed opioids, of which in the 60 days before cohort entry there were at least 30 days of opioids dispensed at an average of at least 30 morphine equivalent units (MEQ) per day. Patients will have no evidence of active cancer; they will have no evidence in the electronic record of MACE; they will not have received methylnatrexone bromide for subcutaneous injection. At the time of the index dispensing of naloxegol or comparison drug, cohort members will furthermore be current users of a dispensed opioid.
Key inclusion criteria (5 listed)
- Patient receives a new dispensing of naloxegol, lubiprostone/linaclotide, or an oral NNPAMORA. A new dispensing is one that occurs with no dispensing for the same drug having occurred in the preceding 182 days. A patient only qualifies once under this criterion for any drug.
- Patients 18 years of age or older at the index date
- Continuous availability of data for at least 183 days immediately before and including the index date
- 90 days of opioid dispensed in the 183 days before and including the index date of which at least 30 days of opioid dispensed at at least 30 MEQ/day in the 60 days before and including index date
- Current users of a dispensed opioid, meaning that the interval between index study drug dispensing and at least 1 prior opioid dispensing is less than the days supply associated with the opioid dispensing
Key exclusion criteria (3 listed)
- Any medical care associated with a diagnosis of cancer in the 183 days before and including the index date; a diagnosis of cancer for this purpose is any diagnostic code of International Classification of Diseases, 9th revision (ICD-9) in the range 140-208 "Malignant neoplasms …" or of the 10th revision (ICD-10) in the range C00-C96, "Malignant neoplasms"
- Dispensing of methylnaltrexone for subcutaneous injection in the 183 days before and including the index date
- Indication in the electronic records of the occurrence of MACE in the 183 days before and including the index date; see Section 9.3.2 "MACE" for screening criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| naloxegolnon-interventional study where naloxegol is prescribed during normal clinical practice | Drug | naloxegol |
| non-PAMORAnon-interventional study where patients are exposed to non-peripherally acting mu-opioid antagonists during the normal course of clinical practice | Drug | non-PAMORA |
Primary outcome
major adverse cardiovascular events
Time frame: can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 8 years
while exposed to naloxegol or comparator exposure, composite of major adverse cardiovascular events which includes cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beth Nordstrom principal investigator
Evidera
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Opioid Induced Constipation, run by Valinor Pharma LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
major adverse cardiovascular events (time frame: can occur anytime through study completion, given no fixed follow-up timepoints, which can range from 1 day to 8 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023; AzTrials last refreshed its copy on 6 Nov 2026.