Pain
Conditions
Brief summary
The main purpose of this study is to compare the pharmacokinetic profile to establish the better controlled liberation of the test product (Tramadol HCL OAD tablets of 200 mg, Labopharm) and its bioavailability in relation with the commercialised reference (Zytram® tablets of 200 mg, Zambon), single dose administered.
Interventions
DRUGTramadol Contramid OAD
1 Tramadol Contramid OAD 200 mg tablet as a single dose
DRUGZytram
1 Zytram 200 mg tablet as a single dose
Sponsors
Labopharm Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects of either gender * Age between 18 and 45 years * Body mass index between 19 and 27kg/m2 * Normal medical history * Normal or no clinically significant physical examination findings * Normal or no clinically significant findings in analytical tests * Negative hepatitis B, hepatitis C or HIV serology * Negative drugs of abuse in urine * Negative pregnancy test in females * The subject understands and accepts the study procedures and grants in writing his/her informed consent
Exclusion criteria
* Did not fulfill the inclusion criteria * Organic disorders or underwent major surgery, within 90 days before study screening * Psychiatric history * Alcohol drink intake greater than 30gr/day * Cigarette smoking greater than 10 cigarettes/day * Excessive consumption of food or beverages containing xanthines (more than five units of coffee, tea or cola per day) * Medical treatment within 30 days before screening, and/or any medication 7 days before starting the study * Participation in other clinical study or donate blood within 90 days before starting this study * Antecedents of gastric, hepatic, renal and other kind of disorder that could affect ADME (absorption, distribution, metabolism or excretion of the study drug) * Hepatitis B, hepatitis C or HIV positive serology * Pregnant or breastfeeding * Clinically relevant hypersensitivities (in particular to drugs) * Woman taking oral contraceptive drugs * Incapable of communicating and cooperating with investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-t) | 48 hours | Area under the plasma concentration versus time curve to the last measured concentration. h=hour |
| AUC (0-∞) | 48 hours | The area under the plasma concentration curve was estimated by extrapolating to infinity AUC0-t. The extrapolation to infinity was done by regression with the last log-transformed data to estimate the terminal area by means of the line that maximized R'2 (coefficient of determination). The units are ng.h/mL. h=hours |
| Cmax | 48 hours | Maximum plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 | 48 hours | Apparent terminal elimination half-life |
| Tmax | 48 hours | Time to maximum plasma concentration |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tramadol Contramid Once A Day Single oral administration of 1x200mg Tramadol OAD tablet according to randomization schedule. There were 2 treatment sequences, each separated by at least one week wash-out period.
OAD: Once-A-Day | 13 |
| Zytram (R) Single oral administration of 1x200mg Zytram tablet according to randomization schedule. There were 2 treatment sequences, each separated by at least one week wash-out period.
OAD: Once-A-Day | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Tramadol Contramid Once A Day | Zytram (R) | 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 | 5 Participants | 8 Participants | 13.0 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 26 | 9 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 26 |
Outcome results
Primary
AUC (0-∞)
The area under the plasma concentration curve was estimated by extrapolating to infinity AUC0-t. The extrapolation to infinity was done by regression with the last log-transformed data to estimate the terminal area by means of the line that maximized R'2 (coefficient of determination). The units are ng.h/mL. h=hours
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol Contramid Once A Day | AUC (0-∞) | 6112 ng.h/mL | Standard Deviation 2078 |
| Zytram (R) | AUC (0-∞) | 5638 ng.h/mL | Standard Deviation 2274 |
Primary
AUC(0-t)
Area under the plasma concentration versus time curve to the last measured concentration. h=hour
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol Contramid Once A Day | AUC(0-t) | 5886 ng.h/mL | Standard Deviation 1843 |
| Zytram (R) | AUC(0-t) | 4761 ng.h/mL | Standard Deviation 1623 |
Primary
Cmax
Maximum plasma concentration
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol Contramid Once A Day | Cmax | 270 ng/mL | Standard Deviation 96 |
| Zytram (R) | Cmax | 219 ng/mL | Standard Deviation 50 |
Secondary
t1/2
Apparent terminal elimination half-life
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tramadol Contramid Once A Day | t1/2 | 7.41 hours | Standard Deviation 2.15 |
| Zytram (R) | t1/2 | 14.92 hours | Standard Deviation 7.11 |
Secondary
Tmax
Time to maximum plasma concentration
Time frame: 48 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tramadol Contramid Once A Day | Tmax | 9.0 hours |
| Zytram (R) | Tmax | 4.5 hours |