Sustained-release Morphine Pharmacokinetics in Roux-en-Y Gastric Bypass Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine whether sustained release morphine pharmacokinetics parameters in patients undergone roux-en-y gastric bypass (RYGB) differ from subjects who did not. Our hypothesis is that exposure is comparable. Indeed, in the Study OBEMO (Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass; NCT00943969) the investigators observed changes in pharmacokinetics parameters for immediate release morphine, probably due to an earlier absorption of the morphine, in agreement with the expected clinical effect of this formulation.

Detailed Description
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This is an open label study with two arms: patients undergone roux-en-y gastric bypass and volunteers who did not matched by sex, age and Body Mass Index (BMI). In the pharmacokinetic visit the subject takes an oral administration of sustained release morphine, 30 mg, then 11 samples are collected during 12 hours.

Official Title
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Study of the Concentrations of Long Acting Morphine After Oral Absorption in Subjects Who Underwent Gastric Bypass (OBEMO 2)

Conditions
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Bypass Complications

Intervention / Treatment
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* Drug: Sustained release morphine sulfate, 30 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RYGB Group (n=12) : Subjects who undergone RYGB for at least 24 months Stable weight since almost one year (or weight loss below 10kg over the last year) Control group (n=12) : Volunteers subjects, matched for age, sex, and Body mass index No history of bariatric surgery Same characteristics Subjects volunteers for the study Age 20-65 years Written consent Exclusion Criteria: Known allergy to morphine or naloxone Patients not affiliated to the french social security system Subjects yet recruited in a study with remuneration Abnormalities in liver function Prothrombin ratio <70% and/ or aspartate transaminase > 5 times the usual values and/ or alanine aminotransferase >5 times the usual values and/ or in renal function (creatinine clearance Modification of Diet in Renal Disease (MDRD) < 60ml/ min Respiratory insufficiency defined by an oximetry below 90% Pregnancy and breastfeeding Use of drugs contra-indicated or not advised with morphine: Agonists-antagonists opioids ( buprenorphine, nalbuphine, pentazocine ), naltrexone Alcohol intake > 30g by day Cough medicine morphine-like ( dextromethorphan, noscapine, pholcodine ) Codeine, ethylmorphine Other morphine agonist ( alfentanil, codeine, dextromoramide, dextropropoxyphene, dihydrocodeine, fentanyl, oxycodone, pethidin, phenoperidine, remifentanil, sufentanil, tramadol ) Barbiturates, benzodiazepines Rifampicin

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects Roux-en-Y-gastric bypass (RYGB)<br>Sustained release morphine sulfate, 30 mg | Drug: Sustained release morphine sulfate, 30 mg<br>* A single oral administration of a capsule of sustained release morphine sulfate, 30 mg, on one day.<br>* Other names: Code : 333 236-9 ; Access market authorisation 3400933323691;|
| Active Comparator: Control volunteers matched with RYGB<br>Sustained release morphine sulfate, 30 mg | Drug: Sustained release morphine sulfate, 30 mg<br>* A single oral administration of a capsule of sustained release morphine sulfate, 30 mg, on one day.<br>* Other names: Code : 333 236-9 ; Access market authorisation 3400933323691;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine area under the curve (AUC0-inf) after its oral administration according to the morphine concentration. |  | During the study visit: morphine concentration at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after its oral administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under ther curve [AUC] of morphine-3-glucuronide, morphine-6-glucuronide |  | During the study visit: concentration at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | 
| Time of the maximum plasma concentration [Tmax] of morphine, morphine-3-glucuronide, morphine-6-glucuronide |  | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | 
| Observed clearance [Cl/F] of morphine, morphine-3-glucuronide, morphine-6-glucuronide | Blood samples gathered from hour 0,5 to hour 12 and urine sample gathered from the start to the end of the study visit. | During the study visit: concentrations at time 0,5h; 1h; 1,5h; 2h; 2,5h; 3h; 4h; 5h; 6h; 8h; 12h after morphine oral administration | 
| Observed Volume of distribution [Vd / F] of morphine, morphine-3-glucuronide, morphine-6-glucuronide |  | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | 
| Plasma Half-Life [T1 /2] of morphine, morphine-3-glucuronide, morphine-6-glucuronide |  | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | 
| Maximum plasma concentration [Cmax] of morphine, morphine-3-glucuronide, morphine-6-glucuronide |  | During the study visit: concentrations at time hour 0,5 ; hour 1; hour 1,5 ; hour 2; hour2,5; hour3; hour 4; hour 5; hour 6; hour 8; hour 12 after morphine oral administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, Roux-en-Y-gastric bypass, pharmacokinetics, Pain, morphine