Healthy
Conditions
Keywords
Healthy volunteers
Brief summary
To determine whether the test product, Labopharm Tramadol HCl Once-A-Day (OAD) 200 mg film-coated tablets, and the reference product, Labopharm Tramadol HCl OAD 200 mg uncoated tablets, are bioequivalent.
Interventions
DRUGTramadol HCl
Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet or Tramadol HCl 200 mg Uncoated Tablets based on randomization schedule.
Sponsors
Labopharm Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects 18 to 55 years of age (inclusive). * Body mass within 10% of the ideal mass in relation to height and age, according to the Body Mass Index (BMI). * Body mass not less than 60 kg. * Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the normal ranges for the relevant laboratory tests (unless the investigator considered the deviation to be irrelevant for the purpose of the study). * Normal electrocardiogram (ECG) and vital signs, or abnormalities which the 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-smoker or past smoker who stopped smoking at least 3 months before entering the study. * For females, the following conditions were to be met: * had been postmenopausal for at least 2 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 1 month before study entry, and * had negative serum pregnancy test at screening. If this test was positive, the subject was to have been excluded from the study before receiving study medication. In the rare circumstance that a pregnancy was discovered after the subjects received study drug, then every attempt must be made to follow such subjects to term, and * must agree to use an accepted method of contraception (i.e., spermicide and barrier methods or spermicide and Intrauterine Device (IUD)). The subject had to agree to continue with the same method throughout the study. Hormonal contraceptives will not be 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 contraceptive agents by females were 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. * A 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 minute or \<45 beats per minute 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 (aspartate aminotransferase), Alanine transaminase (ALT)) \>2 times the upper boundary of the normal range. * Positive urine screen for drugs of abuse. * Positive urine screen for tobacco use (SureStepTM Smoke Check Tests and One-Step Cotinine (COT) Tests). * A serum pregnancy test (beta-hCG) either positive or not performed or lactation. * History of marijuana, barbiturate, amphetamine or narcotic abuse within 12 months prior to study start. * Participation in a tramadol study within the previous 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-t) | 48 hours | Area under plasma concentration versus time curve to the last measurable concentration. Unit is ng.h/mL. h=hours. |
| AUC(0-Inf) | 48 hours | Area under plasma concentration versus time curve extrapolated to infinity. Unit is ng.h/mL. h=hour. |
| Cmax | 48 hours | Maximum plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | 48 hours | Time to the maximum concentration |
| t1/2 | 48 hours | Apparent terminal elimination half-life |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tramadol HCl 200 mg Film-coated Tablets Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule. | 13 |
| Tramadol HCl 200 mg Uncoated Tablets Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Adverse Event | 1 | 1 |
Baseline characteristics
| Characteristic | Tramadol HCl 200 mg Film-coated Tablets | Tramadol HCl 200 mg Uncoated Tablets | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 13 Participants | 26.0 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11.0 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 15.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 25 | 10 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
AUC(0-Inf)
Area under plasma concentration versus time curve extrapolated to infinity. Unit is ng.h/mL. h=hour.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol HCl 200 mg Film-coated Tablets | AUC(0-Inf) | 5328 ng.h/mL | Standard Deviation 1421 |
| Tramadol HCl 200 mg Uncoated Tablets | AUC(0-Inf) | 5175 ng.h/mL | Standard Deviation 1241 |
Primary
AUC(0-t)
Area under plasma concentration versus time curve to the last measurable concentration. Unit is ng.h/mL. h=hours.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol HCl 200 mg Film-coated Tablets | AUC(0-t) | 5181 ng.h/mL | Standard Deviation 1338 |
| Tramadol HCl 200 mg Uncoated Tablets | AUC(0-t) | 5010 ng.h/mL | Standard Deviation 1176 |
Primary
Cmax
Maximum plasma concentration
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol HCl 200 mg Film-coated Tablets | Cmax | 218 ng/mL | Standard Deviation 49 |
| Tramadol HCl 200 mg Uncoated Tablets | Cmax | 209 ng/mL | Standard Deviation 45 |
Secondary
t1/2
Apparent terminal elimination half-life
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol HCl 200 mg Film-coated Tablets | t1/2 | 7.08 hours | Standard Deviation 1.45 |
| Tramadol HCl 200 mg Uncoated Tablets | t1/2 | 7.38 hours | Standard Deviation 1.76 |
Secondary
Tmax
Time to the maximum concentration
Time frame: 48 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tramadol HCl 200 mg Film-coated Tablets | Tmax | 6 hours |
| Tramadol HCl 200 mg Uncoated Tablets | Tmax | 6 hours |