PainPhase 2/3NCT01071499
Pharmacokinetics of Oral Morphine and Pharmacogenomics of CYP2D6 and UGT2B7, in an Urban Pediatric Population Presenting for Elective Surgery
A Phase 2/3 study testing Morphine in people with Pain, run by University of British Columbia at 1 site in Canada.
Trial summary
The purpose of this study is to identify and collect samples from children who have taken a single oral dose of the pain medication morphine, and to determine the genetic differences in the way children metabolize (break down in the body and how it affects them) morphine. Read more about this study
- Who is it for?
- Ages 2 to 6 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain
- What is being tested?
- Morphine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2010to Nov 2012
- Phase
- Phase 2/3
- 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 2 to 6 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 2 - 6 years of age
- ASA 1 \& 2 elective surgical patients - Procedures requiring opioid analgesia - Minimal hospital stay of 4 hrs
- Informed consent
Who cannot join
- Allergy or adverse reaction to morphine
- Contraindication to morphine analgesia, such as a potential difficult airway -- Abnormal hepatic or renal function known by history or available laboratory results
- Current regular opioid use
- Surgical or anesthetic contraindication to oral premedication such as gastro-esophageal reflux disease
- Children with a BMI of <10'ile or >90'ile
- Declines study participation
Trial locations and contacts
1 site in 1 country.
Canada1 site
British Columbia Children's Hospital-Dept of Anesthesia
Vancouver, British Columbia, V6H 3V4
About this study
Official title: Pharmacokinetics of Oral Morphine and Pharmacogenomics of CYP2D6 and UGT2B7, in an Urban Pediatric Population (2 - 6 Years of Age) Presenting for Elective Surgery
The purpose of this study is to identify and collect samples from children who have taken a single oral dose of the pain medication morphine, and to determine the genetic differences in the way children metabolize (break down in the body and how it affects them) morphine.
Read the detailed description
Hypothesis:
Oral morphine will produce more reliable peak plasma morphine concentrations and more reliable analgesia than codeine, which is currently the drug of choice.
Background:
Codeine is the most commonly used oral opiate for analgesia in children. Codeine is a pro-drug that requires activation by the isozyme CYP2D6. Genetically determined variations in the activity of CYP2D6 can result in inappropriately low analgesic efficacy due to inadequate conversion of the drug in "poor-metabolizers" and conversely, adverse reactions such as respiratory depression and death in "ultra-metabolizers". In some ethnic groups as many as 40% of patients may be susceptible to concentration-dependent toxicity from greater than expected metabolism of codeine to morphine. We hypothesize that oral morphine is a feasible and safe alternative to codeine. The primary aim of this study is to define and trial an appropriate dose of morphine to provide children with effective and reliable perioperative analgesia with a minimum risk of adverse drug effects. A secondary aim is to investigate the pharmacogenetics of codeine and morphine metabolism in children.
Specific Objectives:
The pharmacokinetic properties of 3 (0.1 mg/kg, 0.2 mg/kg or 0.3 mg/kg) doses of oral morphine will be described. We will determine the dose of oral morphine that results in a peak plasma concentration that occurs within 60 - 90 min and results in the analgesic therapeutic range (10 - 40 ng/mL). Pharmacogenetic profiles for two key enzymes involved in codeine and morphine metabolism (CYP2D6 and UGT2B7) will be determined.
Methods:
After obtaining institutional review board approval, and written parental informed consent, we will recruit 45 children for Phase I aged 2-6 years undergoing elective surgery. A perceived ethnicity questionnaire will also be administered. Subjects recruited for Phase I will be block assigned to one of the three doses of morphine. In Phase I, sampling will be done for 4 hrs to determine the key pharmacokinetic parameters including Tmax, Cmax and AUC. Monitoring will occur throughout and analgesic efficacy and adverse effects will be measured post-operatively. All subjects will receive 24 hr telephone follow up for analgesic efficacy and adverse drug effects.
Data Analysis: All continuous parametric data (weight, age, BMI) will be analyzed using t-tests. Non-parametric ordinal data such as pain scores will be analyzed by the Mann-Whitney U test.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
One dose of morphine (0.1 mg/kg)
MorphineDrug
One dose of morphine (0.2 mg/kg)
MorphineDrug
One dose of morphine (0.3 mg/kg)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Subjects recruited will be block assigned to one of the three doses of morphine. Sampling will be done for 4 hrs to determine the key pharmacokinetic parameters. Receives: Drug: Morphine |
| 2 | Active comparator | Subjects recruited will be block assigned to one of the three doses of morphine. Sampling will be done for 4 hrs to determine the key pharmacokinetic parameters. Receives: Drug: Morphine |
| 3 | Active comparator | Subjects recruited will be block assigned to one of the three doses of morphine. Sampling will be done for 4 hrs to determine the key pharmacokinetic parameters. Receives: Drug: Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
1 mL blood sample will be obtained at 30, 60, 90, 120, 180 and 240 min after morphine administration.
Measured: 4 hours
Secondary outcomes (1)
Face, Legs, Activity, Cry and Consolability (FLACC) pain score
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2010 (estimated)
- Study startMar 2010
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carolyne Montgomery, University of British Columbia
- Investigators
- Carolyne Montgomery, Dr., Principal investigator, University of British ColumbiaGillian Lauder, Dr., Study director, University of British ColumbiaKatherine Brand, Dr., Study director, University of British ColumbiaBruce Carleton, Dr., Study director, University of British ColumbiaGideon Koren, Dr., Study director, University of British ColumbiaMichael Rider, Dr., Study director, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01071499
- Sponsor's protocol ID
- H09-03286
- Status last verified
- May 2017
- First submitted
- 17 Feb 2010
- Last updated
- 5 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Velez de Mendizabal N, Jimenez-Mendez R, Cooke E, Montgomery CJ, Dawes J, Rieder MJ, Aleksa K, Koren G, Jacobo-Cabral CO, Gonzalez-Ramirez R, Castaneda-Hernandez G, Carleton BC. A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose. Clin Pharmacokinet. 2015 Oct;54(10):1083-90. doi: 10.1007/s40262-015-0256-4.
PubMed 25773480
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Oral Morphine and Pharmacogenomics of CYP2D6 and UGT2B7, in an Urban Pediatric Population (2 - 6 Years of Age) Presenting for Elective Surgery
- ClinicalTrials.gov ID
- NCT01071499
- Acronym / sponsor ID
- H09-03286
- Conditions
- Pain
- Keywords
- pharmacokinetics, pharmacogenetics, morphine, children
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 19 Feb 2010 (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 purpose of this study is to identify and collect samples from children who have taken a single oral dose of the pain medication morphine, and to determine the genetic differences in the way children metabolize (break down in the body and how it affects them) morphine.
Detailed description
Hypothesis:
Oral morphine will produce more reliable peak plasma morphine concentrations and more reliable analgesia than codeine, which is currently the drug of choice.
Background:
Codeine is the most commonly used oral opiate for analgesia in children. Codeine is a pro-drug that requires activation by the isozyme CYP2D6. Genetically determined variations in the activity of CYP2D6 can result in inappropriately low analgesic efficacy due to inadequate conversion of the drug in "poor-metabolizers" and conversely, adverse reactions such as respiratory depression and death in "ultra-metabolizers". In some ethnic groups as many as 40% of patients may be susceptible to concentration-dependent toxicity from greater than expected metabolism of codeine to morphine. We hypothesize that oral morphine is a feasible and safe alternative to codeine. The primary aim of this study is to define and trial an appropriate dose of morphine to provide children with effective and reliable perioperative analgesia with a minimum risk of adverse drug effects. A secondary aim is to investigate the pharmacogenetics of codeine and morphine metabolism in children.
Specific Objectives:
The pharmacokinetic properties of 3 (0.1 mg/kg, 0.2 mg/kg or 0.3 mg/kg) doses of oral morphine will be described. We will determine the dose of oral morphine that results in a peak plasma concentration that occurs within 60 - 90 min and results in the analgesic therapeutic range (10 - 40 ng/mL). Pharmacogenetic profiles for two key enzymes involved in codeine and morphine metabolism (CYP2D6 and UGT2B7) will be determined.
Methods:
After obtaining institutional review board approval, and written parental informed consent, we will recruit 45 children for Phase I aged 2-6 years undergoing elective surgery. A perceived ethnicity questionnaire will also be administered. Subjects recruited for Phase I will be block assigned to one of the three doses of morphine. In Phase I, sampling will be done for 4 hrs to determine the key pharmacokinetic parameters including Tmax, Cmax and AUC. Monitoring will occur throughout and analgesic efficacy and adverse effects will be measured post-operatively. All subjects will receive 24 hr telephone follow up for analgesic efficacy and adverse drug effects.
Data Analysis: All continuous parametric data (weight, age, BMI) will be analyzed using t-tests. Non-parametric ordinal data such as pain scores will be analyzed by the Mann-Whitney U test.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: MorphineSubjects recruited will be block assigned to one of the three doses of morphine. Sampling will be done for 4 hrs to determine the key pharmacokinetic parameters. |
| 2 | Active comparator | Drug: MorphineSubjects recruited will be block assigned to one of the three doses of morphine. Sampling will be done for 4 hrs to determine the key pharmacokinetic parameters. |
| 3 | Active comparator | Drug: MorphineSubjects recruited will be block assigned to one of the three doses of morphine. Sampling will be done for 4 hrs to determine the key pharmacokinetic parameters. |
Who may qualify
- Ages
- 2 to 6 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 2 - 6 years of age
- ASA 1 \& 2 elective surgical patients - Procedures requiring opioid analgesia - Minimal hospital stay of 4 hrs
- Informed consent
Key exclusion criteria (6 listed)
- Allergy or adverse reaction to morphine
- Contraindication to morphine analgesia, such as a potential difficult airway -- Abnormal hepatic or renal function known by history or available laboratory results
- Current regular opioid use
- Surgical or anesthetic contraindication to oral premedication such as gastro-esophageal reflux disease
- Children with a BMI of <10'ile or >90'ile
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 |
|---|---|---|
| MorphineOne dose of morphine (0.1 mg/kg) | Drug | 1 |
| MorphineOne dose of morphine (0.2 mg/kg) | Drug | 2 |
| MorphineOne dose of morphine (0.3 mg/kg) | Drug | 3 |
Primary outcome
1 mL blood sample will be obtained at 30, 60, 90, 120, 180 and 240 min after morphine administration.
Time frame: 4 hours
1 secondary outcome
Face, Legs, Activity, Cry and Consolability (FLACC) pain score
Time frame: 4 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2017.
- Derived from this study: PubMed 25773480Velez de Mendizabal N, Jimenez-Mendez R, Cooke E, Montgomery CJ, Dawes J, Rieder MJ, Aleksa K, Koren G, Jacobo-Cabral CO, Gonzalez-Ramirez R, Castaneda-Hernandez G, Carleton BC. A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose. Clin Pharmacokinet. 2015 Oct;54(10):1083-90. doi: 10.1007/s40262-015-0256-4.
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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.
Carolyne Montgomery, Dr. principal investigator
University of British Columbia
Gillian Lauder, Dr. study director
University of British Columbia
Katherine Brand, Dr. study director
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Morphine in people with Pain, run by University of British Columbia at 1 site in Canada.
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 3 inclusion and 6 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: finished, as of the sponsor's last update on 5 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
1 mL blood sample will be obtained at 30, 60, 90, 120, 180 and 240 min after morphine administration. (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01071499, which also lists 1 linked publication.
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 5 Jul 2017.