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

NCT ID: NCT02641301

Last Updated: 2016-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2017-03-31

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.

Conditions

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Bypass Complications

Keywords

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obesity Roux-en-Y-gastric bypass pharmacokinetics Pain morphine

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Subjects Roux-en-Y-gastric bypass (RYGB)

Sustained release morphine sulfate, 30 mg

Group Type EXPERIMENTAL

Sustained release morphine sulfate, 30 mg

Intervention Type DRUG

A single oral administration of a capsule of sustained release morphine sulfate, 30 mg, on one day.

Control volunteers matched with RYGB

Sustained release morphine sulfate, 30 mg

Group Type ACTIVE_COMPARATOR

Sustained release morphine sulfate, 30 mg

Intervention Type DRUG

A single oral administration of a capsule of sustained release morphine sulfate, 30 mg, on one day.

Interventions

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Sustained release morphine sulfate, 30 mg

A single oral administration of a capsule of sustained release morphine sulfate, 30 mg, on one day.

Intervention Type DRUG

Other Intervention Names

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Code : 333 236-9 ; Access market authorisation 3400933323691

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
Minimum Eligible Age

20 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Hopital Lariboisière

OTHER

Sponsor Role lead

Responsible Party

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Célia Lloret-Linares, MD PhD

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jean-Francois JB Bergmann, MD, PhD

Role: STUDY_DIRECTOR

Hopital Lariboisiere

Locations

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Therapeutic Research Unit, Department of Internal Medicine, Hospital Lariboisiere

Paris, , France

Site Status

Hopital Pitie Salpetriere

Paris, , France

Site Status

Countries

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France

References

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Skottheim IB, Stormark K, Christensen H, Jakobsen GS, Hjelmesaeth J, Jenssen T, Reubsaet JL, Sandbu R, Asberg A. Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients. Clin Pharmacol Ther. 2009 Sep;86(3):311-8. doi: 10.1038/clpt.2009.82. Epub 2009 Jun 3.

Reference Type BACKGROUND
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Hamad GG, Helsel JC, Perel JM, Kozak GM, McShea MC, Hughes C, Confer AL, Sit DK, McCloskey CA, Wisner KL. The effect of gastric bypass on the pharmacokinetics of serotonin reuptake inhibitors. Am J Psychiatry. 2012 Mar;169(3):256-63. doi: 10.1176/appi.ajp.2011.11050719.

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Raebel MA, Newcomer SR, Reifler LM, Boudreau D, Elliott TE, DeBar L, Ahmed A, Pawloski PA, Fisher D, Donahoo WT, Bayliss EA. Chronic use of opioid medications before and after bariatric surgery. JAMA. 2013 Oct 2;310(13):1369-76. doi: 10.1001/jama.2013.278344.

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Hasselstrom J, Sawe J. Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations. Clin Pharmacokinet. 1993 Apr;24(4):344-54. doi: 10.2165/00003088-199324040-00007.

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Reference Type BACKGROUND
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Lloret-Linares C, Hirt D, Bardin C, Bouillot JL, Oppert JM, Poitou C, Chast F, Mouly S, Scherrmann JM, Bergmann JF, Decleves X. Effect of a Roux-en-Y gastric bypass on the pharmacokinetics of oral morphine using a population approach. Clin Pharmacokinet. 2014 Oct;53(10):919-30. doi: 10.1007/s40262-014-0163-0.

Reference Type BACKGROUND
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Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013 Apr;23(4):427-36. doi: 10.1007/s11695-012-0864-0.

Reference Type BACKGROUND
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Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010 Jan;11(1):41-50. doi: 10.1111/j.1467-789X.2009.00614.x. Epub 2009 Jun 2.

Reference Type BACKGROUND
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Skottheim IB, Jakobsen GS, Stormark K, Christensen H, Hjelmesaeth J, Jenssen T, Asberg A, Sandbu R. Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch. Clin Pharmacol Ther. 2010 Jun;87(6):699-705. doi: 10.1038/clpt.2010.32. Epub 2010 May 5.

Reference Type BACKGROUND
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Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301-16. doi: 10.1146/annurev.med.080708.082713.

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Lotsch J, Weiss M, Ahne G, Kobal G, Geisslinger G. Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers. Anesthesiology. 1999 Apr;90(4):1026-38. doi: 10.1097/00000542-199904000-00016.

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Other Identifiers

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OBEMO2

Identifier Type: -

Identifier Source: org_study_id