Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02329561
Recruitment Status : Completed
First Posted : December 31, 2014
Last Update Posted : December 31, 2014
Sponsor:
Collaborators:
Labopharm Inc.
MDS Pharma Services
Information provided by (Responsible Party):
France Varin, Université de Montréal

Tracking Information
First Submitted Date  ICMJE December 19, 2014
First Posted Date  ICMJE December 31, 2014
Last Update Posted Date December 31, 2014
Study Start Date  ICMJE January 2007
Actual Primary Completion Date February 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 30, 2014)
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 [ Time Frame: 48 hours ]
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 healthy adult young and elderly subjects. Plasma samples were taken at 16 timepoints throughout 48 hours and evaluated for plasma concentrations of (+)- and (-)- tramadol
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 30, 2014)
  • To characterise and compare threshold of current perception in young and elderly subjects [ Time Frame: 30 hours ]
    Healthy adult young and elderly subjects were tested to determine the milliamperes of current that resulted in perception of an electrical stimulus in the non-dominant forefinger at 15 timepoints throughout 30 hours using an electrically stimulated pain model after treatment with active drug and placebo with random assignment of treatment sequence (placebo then tramadol or tramadol then placebo)
  • To characterise and compare threshold of pain tolerance in young and elderly subjects [ Time Frame: 30 hours ]
    Healthy adult young and elderly subjects were tested to determine the milliamperes of current they were willing to tolerate at 15 timepoints throughout 30 hours using an electrically stimulated pain model after treatment with active drug and placebo with random assignment of treatment sequence (placebo then tramadol or tramadol then placebo)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PK PD of the Enantiomers of Tramadol and O-desmethyltramadol in Elderly and Young Subjects
Official Title  ICMJE 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
Brief 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE
  • Aging
  • Pain
Intervention  ICMJE
  • Drug: Tramadol extended release 200 mg
    Tramadol extended release 200 mg: Administration of a single 200mg tramadol extended-release tablet
    Other Name: Tramadol Contramid 200 mg extended-release
  • Behavioral: CP/T
    Subjects were evaluated for perception and tolerance of electrical current. An experimentally induced pain model utilizing electrical stimulation from the FDA approved Neurometer, as the painful stimulus was used to assess Current Perception Threshold and Pain Tolerance Threshold (CP/T) in young and elderly subjects following administration of tramadol and of placebo.
    Other Name: Electrically stimulated experimental pain model (ESEPM)
  • Drug: Placebo
    Administration of a single placebo tablet identical in appearance to a 200mg tramadol extended-release tablet
    Other Name: sugar pill
Study Arms  ICMJE
  • Active Comparator: Tramadol extended release and CP/T
    Tramadol extended release: 200mg Single-dose, extended-release, once-daily, tablet; Current Perception and Tolerance (CP/T)
    Interventions:
    • Drug: Tramadol extended release 200 mg
    • Behavioral: CP/T
  • Placebo Comparator: Placebo and CP/T
    Single-dose, placebo identical in appearance to an extended release once-daily tablet; Current Perception and Tolerance (CP/T)
    Interventions:
    • Behavioral: CP/T
    • Drug: Placebo
Publications * Skinner-Robertson S, Fradette C, Bouchard S, Mouksassi MS, Varin F. Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-Release Tablets to Elderly and Young Subjects. Drugs Aging. 2015 Dec;32(12):1029-43. doi: 10.1007/s40266-015-0315-4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 30, 2014)
35
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2007
Actual Primary Completion Date February 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02329561
Other Study ID Numbers  ICMJE MDT1-20
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party France Varin, Université de Montréal
Study Sponsor  ICMJE Université de Montréal
Collaborators  ICMJE
  • Labopharm Inc.
  • MDS Pharma Services
Investigators  ICMJE
Principal Investigator: France Varin, BPharm, PhD Université de Montréal
PRS Account Université de Montréal
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP