A Study to Compare the Bioavailability of Two Tramadol Hydrochloride Tablet Products (50 mg and 200 mg, Respectively) at Steady-state Under Fasting Conditions

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Labopharm Inc.
ClinicalTrials.gov Identifier:
NCT00834288
First received: January 30, 2009
Last updated: April 24, 2012
Last verified: April 2012
  Purpose

The purpose of this study was to compare the pharmacokinetic profiles at steady-state of the test product, Tramadol HCl Once-A-Day (OAD) 200 mg tablets and the reference product, Tramadol HCl 50 mg (IR) tablets (Ortho-McNeil Ultram®). For this purpose, the extent of absorption of tramadol and formation of O-desmethyltramadol (measures of systemic exposure) after multiple administration of 50 mg 6-hourly at 07:30, 13:30, 19:30 and 01:30 (reference product) and 200 mg 24-hourly at 07:30 (test product), were compared.


Condition Intervention Phase
Healthy Subjects
Pharmacokinetics
Bioavailability
Drug: Tramadol HCl
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study to Compare the Bioavailability of Two Tramadol Hydrochloride Tablet Products (50 mg and 200 mg, Respectively) at Steady-state Under Fasting Conditions

Resource links provided by NLM:


Further study details as provided by Labopharm Inc.:

Primary Outcome Measures:
  • Area Under the Plasma Concentration Versus Time Data Pairs at Steady State (AUCss) [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]

    Area under the plasma concentration versus time data pairs over 24 hours (24h) at steady state, on day 5.

    ss = steady state. AUCss is also known as AUCtau.



Secondary Outcome Measures:
  • Maximum Plasma Concentration at Steady State(Cmax,ss) [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]
    Maximum plasma concentration over 24 hours (24h) at steady state, on day 5. ss = steady state.

  • Minimum Plasma Concentration at Steady State(Cmin,ss) [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]
    Minimum plasma concentration over 24 hours (24h) at steady state on day 5. ss = steady state.

  • Time to Peak Exposure (Tmax) [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]
    Time to peak exposure over 24 hours (24h) at steady state on day 5.

  • Percentage Peak-trough Fluctuation (% PTF) [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]

    Percentage peak-trough fluctuation over 24 hours (24h) at steady state on day 5.

    Percent peak-to-trough fluctuation is calculated as (Cmax - Cmin)/Cav*100, where Cmax is the maximum observed concentration, Cmin is the minimum observed concentration and Cav is the average concentration over 24 hours (where Cav = AUCss/24).


  • Percentage Swing [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]

    Percentage swing is a pharmacokinetic parameter recommended by the FDA for submission and is calculated as follows:((Cmax,ss - Cmin,ss)/Cmin,ss)*100. It was calculated over 24 hours on day 5.

    Where:

    Cmax,ss = Maximum concentration at steady state; Cmin,ss = Minimum concentration at steady state.


  • Half-value Duration (HVD) [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]
    Time over which plasma concentrations were above one half Cmax on day 5. 24h = 24 hours.

  • Plateau Time (T75%Cmax) [ Time Frame: 24 hours (day 5) ] [ Designated as safety issue: No ]
    Time over which plasma concentrations were above 75% Cmax on day 5. 24h = 24 hours.


Enrollment: 26
Study Start Date: June 2003
Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: 1x200 mg Tramadol HCl OAD tablet daily Drug: Tramadol HCl
1x200 mg Tramadol HCl OAD tablet daily
Active Comparator: 2: 1x50 mg Tramadol HCl IR (Ultram®) tablet 6-hourly Drug: Tramadol HCl
1x50 mg Tramadol HCl IR (Ultram®) tablet 6-hourly

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy, non-smoking, male and female subjects between the ages 18 to 55 years (inclusive).
  • Body mass within 10% of the ideal mass in relation to height and age, according to the BMI
  • Body mass not less than 70 kg.
  • Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results with the "normal ranges" for the relevant laboratory tests (unless the clinical investigator considers the deviation to be irrelevant for the purpose of the study).
  • Normal ECG and vital signs, or abnormalities which the clinical investigator did not consider a disqualification for participation in the study
  • Willingness to undergo a pre-study physical examination and pre- and post-study laboratory investigations.
  • Ability to comprehend and willingness to sign both statements of Informed Consent (for screening and phase-related procedures)
  • Non-smokers or past smokers who stopped smoking at least three months before entering the study
  • For females, the following conditions had to be met:

    • had been postmenopausal for at least two years, or
    • had been surgically sterilized, or
    • was of childbearing potential, and all of the following conditions were met:
    • had a normal menstrual flow within one month before study entry, and
    • had negative urine pregnancy test at screening and on Day 1 of each study period. If the result of either test was positive, the subject would have been excluded from the study before receiving study medication.
    • had to agree to use an accepted method of contraception. The subject had to agree to continue with the same method throughout the study. Hormonal contraceptives were not allowed.

Exclusion Criteria:

  • Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
  • History of, or current compulsive alcohol abuse (> 10 drinks weekly), or regular exposure to other substances of abuse.
  • Use of any medication, prescribed or over-the-counter, within 2 weeks prior to the first administration of study medication except if this would not have affected the outcome of the study in the opinion of the clinical investigator. Use of hormonal contraceptives agents by females was not allowed.
  • Participation in another study with an experimental drug within 8 weeks before the first administration of study medication.
  • Treatment within the previous 3 months with any drug with a well-defined potential for adversely affecting a major organ or system with evidence to this effect.
  • Major illness during the 3 months before commencement of the screening period.
  • History of hypersensitivity to the study drug or any related drugs.
  • History of bronchial asthma.
  • History of epilepsy.
  • Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome.
  • Donation or loss of blood equal to or exceeding 500 ml during the 8 weeks before the first administration of study medication.
  • Diagnosis of hypotension made during the screening period.
  • Diagnosis of hypertension made during the screening period or current diagnosis of hypertension.
  • Resting pulse of > 100 beats per minutes or < 45 beats per minutes during the screening period, either supine or standing.
  • Positive testing for hepatitis B antigen.
  • Significant liver disease, defined as active hepatitis or elevated liver enzymes (e.g., AST, ALT) > 3 times the upper boundary of the normal range.
  • Positive urine screen for drugs of abuse.
  • Positive urine screen for tobacco use.
  • History of marijuana, barbiturates, amphetamine, or narcotic abuse within 12 months prior to study start.
  • Previous participation in a tramadol study.
  • pregnancy or lactation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
Publications:
Responsible Party: Labopharm Inc.
ClinicalTrials.gov Identifier: NCT00834288     History of Changes
Other Study ID Numbers: MDT1-009
Study First Received: January 30, 2009
Results First Received: April 8, 2009
Last Updated: April 24, 2012
Health Authority: South Africa: Medicines Control Council

Keywords provided by Labopharm Inc.:
Healthy subjects
Pharmacokinetics
Bioavailability

Additional relevant MeSH terms:
Tramadol
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics, Opioid

ClinicalTrials.gov processed this record on July 28, 2014