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PK PD of the Enantiomers of Tramadol and O-desmethyltramadol in Elderly and Young Subjects

Information source: Université de Montréal
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Aging; Pain

Intervention: Tramadol extended release 200 mg (Drug); CP/T (Behavioral); Placebo (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Université de Montréal

Official(s) and/or principal investigator(s):
France Varin, BPharm, PhD, Principal Investigator, Affiliation: Université de Montréal

Summary

This study evaluates the pharmacokinetics and pharmacodynamics of the enantiomers of tramadol and O-desmethyltramadol (ODM) in generally healthy young and elderly adults. Using a randomised, double-blind, crossover design, participants were administered a single 200mg tramadol extended-release tablet and placebo.

Clinical Details

Official title: Comparative, Randomized, Double-Blind, Single-Dose, 2-way Crossover Study to Evaluate the Pharmacokinetics and Analgesic Effect of Labopharm Tramadol Contramid® OAD 200 mg Tablets or Placebo in Healthy Young and Elderly Adult Volunteers

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Primary outcome: To characterise and compare the pharmacokinetic parameters of AUC 0-t, AUCinf, Cmax, tmax, t½, CL/F, Varea/F, Ae 0 48, Rmax and CLr for the enantiomers of tramadol and O-desmethyltramadol in young and elderly subjects

Secondary outcome:

To characterise and compare threshold of current perception in young and elderly subjects

To characterise and compare threshold of pain tolerance in young and elderly subjects

Detailed description: The pharmacokinetics of the enantiomers of tramadol and O-desmethyltramadol (ODM) have not been extensively studied in elderly patients. Given the importance of hepatic function in the metabolism of tramadol into the more potent ODM metabolite and the fact that tramadol is primarily renally excreted, age-related changes in hepatic and renal function may affect the pharmacokinetics and pharmacodynamics of tramadol. Data on the pharmacokinetics of tramadol, the ODM metabolite and their enantiomers will provide important information as to the source of any differences in the metabolism or elimination of Tramadol Contramid® OAD in the elderly as compared to younger subjects. Differences in the PK of tramadol and O-desmethyltramadol could result in differences in Pharmacodynamics of tramadol, specifically in analgesic effect. An Electrically Stimulated Pain Model was used to evaluate any differences in current perception and pain tolerance between the age groups.

Eligibility

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Healthy adult male or female volunteers, 18-40 years of age.

- Adult male or female volunteers aged 75 years or more

- Subjects with a BMI less than 35 kg/m2.

- Generally healthy, elderly subjects with mild renal impairment (creatinine clearance

50-80 mL/min or glomerular filtration rate ≥ 50 mL/min/1. 73 m2) or mild hepatic impairment (Child-Pugh Class A)

- Medically stable healthy subjects with non-clinically significant laboratory

profiles, vital signs and ECGs.

- Subjects will be non-smokers for at least 3 months prior to the first dose or

consistent moderate smokers (fewer than 10 cigarettes per day) for at least 3 months prior to the first dose.

- Females of childbearing potential must be using medically acceptable birth control

methods

- Voluntary written informed consent

Exclusion Criteria:

- History or presence of significant unstable or untreated cardiovascular, pulmonary,

hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease.

- alcoholism or drug abuse within the past year;

- previous or current opioid dependency or other substance abuse or dependence, other

than nicotine;

- hypersensitivity or idiosyncratic reaction to tramadol hydrochloride, codeine,

opioids or other synthetic opioids of the aminocyclohexanol group;

- seizures (other than infantile febrile seizures);

- significant head trauma.

- Subjects who tested positive at screening for HIV, HBsAg or HCV.

- Subjects whose sitting blood pressure is less than 110/60 mmHg at screening or prior

to dosing.

- Subjects whose pulse is lower than 55 b. p.m. at screening or prior to dosing for

young subjects or less than 60 b. p.m at screening or prior to dosing for the elderly subjects.

- Subjects who have used any drugs or substances known to be strong inhibitors of CYP

enzymes (formerly known as cytochrome P450 enzymes) within 10 days prior to the first dose.

- Subjects who have used any drugs or substances known to be strong inducers of CYP

enzymes (formerly known as cytochrome P450 enzymes) within 28 days prior to the first dose.

- Subjects who are revealed upon genotyping to be CYP2D6 poor metabolisers.

- Subjects who have received monoamine oxidase inhibitors (MAOI) or antidepressants

(tricyclic or SSRIs), within 28 days prior to the first dose.

- Subjects who have received drugs belonging to the opioids/analgesic class, within 5

elimination half-lives prior to the first dose.

- Subjects who have received coumarin derivatives (e. g warfarin) or digoxin, within 28

days prior to the first dose.

- Subjects who have received CNS depressant drugs (such as benzodiazepines,

barbiturates, sedative H1 antihistamines, neuroleptics, some beta-blockers, anxiolytics other than benzodiazepines), tricyclic compounds (such as cyclobenzaprine, promethazine), drugs increasing serotonin levels or thalidomide within 5 elimination half-lives prior to the first dose.

- Subjects with significant liver disease (Child-Pugh Score greater than or equal to

7).

- Significant renal disease as determined by the Cockcroft-Gault formula

- Bowel disease affecting absorption.

- Major illness requiring hospitalization during the last 3 months prior to the first

dose.

- Previous failure of treatment with tramadol or discontinuation of treatment with

tramadol due to adverse events.

- Subjects who have been on a special diet (for whatever reason) during the 28 days

prior to the first dose and throughout the study.

- Subjects who have any condition that, in the opinion of the Investigator, makes the

subject unsuitable for the study.

- Subjects who donated significant amounts of blood in the last year

- Subjects who have participated in another clinical trial within 28 days prior to the

first dose.

- Subjects who are unable to tolerate the training for the ESEPM.

Locations and Contacts

Additional Information

Starting date: January 2007
Last updated: December 30, 2014

Page last updated: August 23, 2015

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