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AgingPhase 1NCT02329561

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

A Phase 1 study testing Tramadol extended release 200 mg and CP/T in people with Aging and Pain, run by Université de Montréal.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Aging, Pain
What is being tested?
Tramadol extended release 200 mg and CP/T
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
35 participants
Where
No sites listed yet
Study dates
Jan 2007to Feb 2007
Phase
Phase 1
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 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
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  • 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.

About this study

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

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.

Read the 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.

Conditions
Aging, Pain
Being tested
Tramadol extended release 200 mg, CP/T, Placebo
Keywords
Pharmacokinetics, Opioid, Geriatric, Pharmacodynamics
Medical subject headings
Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tramadol extended release 200 mgDrug

    Also called Tramadol Contramid 200 mg extended-release

    Tramadol extended release 200 mg: Administration of a single 200mg tramadol extended-release tablet

  • CP/TBehavioural

    Also called Electrically stimulated experimental pain model (ESEPM)

    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.

  • PlaceboDrug

    Also called sugar pill

    Administration of a single placebo tablet identical in appearance to a 200mg tramadol extended-release tablet

Study groups in NCT02329561
Study groupRoleWhat they receive
Tramadol extended release and CP/TActive comparatorTramadol extended release: 200mg Single-dose, extended-release, once-daily, tablet; Current Perception and Tolerance (CP/T)
Receives: Drug: Tramadol extended release 200 mg; Behavioral: CP/T
Placebo and CP/TPlacebo comparatorSingle-dose, placebo identical in appearance to an extended release once-daily tablet; Current Perception and Tolerance (CP/T)
Receives: Behavioral: CP/T; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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

    Measured: 48 hours

Secondary outcomes (2)

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

    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)

    Measured: 30 hours

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

    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)

    Measured: 30 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2014 (estimated)
  2. Study startJan 2007
  3. Primary completionFeb 2007
  4. Study completionFeb 2007

Resources

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 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02329561
Sponsor's protocol ID
MDT1-20
Status last verified
Dec 2014
First submitted
19 Dec 2014
Last updated
31 Dec 2014
Results posted
No
Data monitoring committee
No

Publications

  • Robertson SS, Mouksassi MS, Varin F. Population Pharmacokinetic/Pharmacodynamic Modeling of O-Desmethyltramadol in Young and Elderly Healthy Volunteers. Drugs Aging. 2019 Aug;36(8):747-758. doi: 10.1007/s40266-019-00681-w.

    PubMed 31161580

  • 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.

    PubMed 26508138

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tramadol extended release 200 mg and CP/T in people with Aging and Pain, run by Université de Montréal.

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 8 inclusion and 26 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 31 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

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). 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 NCT02329561, which also lists 2 linked publications.

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 31 Dec 2014.

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