Study of Two Tramadol Contramid® OAD 300 mg Controlled-Re... | NCT00834912

Status Module

Label	Type	Intervention Names
1: Tramadol HCl (Confab Laboratories) fasting	Experimental	Drug: Tramadol hydrochloride
2: Tramadol HCl (Confab Laboratories) fed	Experimental	Drug: Tramadol HCl
3: Tramadol HCl (Trillium Healthcare) fasting	Experimental	Drug: Tramadol HCl

Name	Type	Description	Arm Group Labels	Other Names
Tramadol hydrochloride	Drug	1x300mg Tramadol Hydrochloride (HCl) tablet (Confab Laboratories), fasting condition. Taken for one treatment period only, then subjects switched treatment at each period as per randomization schedule. Results are presented per treatment group overall.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
AUC(0-t)	Area under the plasma concentration (AUC) versus time curve to the last measurable concentration.	48 hours
AUC(0-∞)	The area under the plasma concentration (AUC) 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	48 hours
Cmax	Maximum plasma concentration (Cmax)	48 hours

Measure	Description	Time Frame
Tmax	Time to maximum plasma concentration (Tmax)	48 hours
t1/2	Apparent terminal elimination half-life (t1/2)	48 hours

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, non-smoker, ≥18 and ≤55 years of age.
Capable of consent.
Body Mass Index (BMI) ≥19.0 and <30.0 kg/m2.

Exclusion Criteria:

Clinically significant illness or surgery within 4 weeks prior to dosing.
Any clinically significant abnormality or abnormal laboratory test results found during medical screening.
Any reason which, in the opinion of the Medical Sub-Investigator, would prevent the subject from participating in the study.
Positive test for hepatitis B, hepatitis C, or HIV at screening.
Electrocardiogram (ECG) abnormalities (clinically significant) or vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 50 or over 100 beats per minute [bpm]) at screening.
History of significant alcohol abuse or drug abuse within one year prior to the screening visit.
Regular use of alcohol within six months prior to the screening visit (more than fourteen units of alcohol per week [1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
Use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine [PCP] and crack) within 1 year prior to the screening visit or positive urine drug screen at screening.
History of allergic reactions to tramadol or other related drugs.
Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; examples of inhibitors: antidepressants (Selective serotonin reuptake inhibitors [SSRIs]), cimetidine, diltiazem, macrolides, imidazoles, neuroleptics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to administration of the study medication.
Use of an investigational drug or participation in an investigational study within 30 days prior to dosing.
Clinically significant history or presence of any gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the drug.
Any clinically significant history or presence of neurological, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric, or metabolic disease.
Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products (including natural food supplements, vitamins, garlic as a supplement) within 7 days prior to administration of study medication, except for topical products without systemic absorption and hormonal contraceptives.
Difficulty to swallow study medication.
Use of any tobacco products in the 3 months preceding drug administration.
Any food allergy, intolerance, restriction or special diet that, in the opinion of the Medical Sub-Investigator, could contraindicate the subject's participation in this study.
A depot injection or an implant of any drug (other than hormonal contraceptives) within 3 months prior to administration of study medication.
Donation of plasma (500 mL) within 7 days prior to drug administration. Donation or loss of whole blood (excluding the volume of blood that will be drawn during the screening procedures of this study) prior to administration of the study medication as follows:
50 mL to 499 mL of whole blood within 30 days,
more than 499 mL of whole blood within 56 days prior to drug administration.
Consumption of food or beverages containing grapefruit (e.g. fresh, canned, or frozen) within 7 days prior to administration of the study medication.
History or presence of substance addiction.
History of anaphylactoid reactions to codeine and other opioids.
History of respiratory depression.
History of increased intracranial pressure or head injury.
History or presence of asthma, chronic obstructive pulmonary disease or other pulmonary condition that may predispose to hypoventilation.
Opioid consumption in the 3 months preceding drug administration or history of drug dependence to any opioids.
Positive urine pregnancy test at screening.
Breast-feeding subject.
Female subjects of childbearing potential having unprotected sexual intercourse with any non-sterile male partner (i.e. male who has not been sterilized by vasectomy for at least 6 months) within 14 days prior to study drug administration. Acceptable methods of contraception are:
intra-uterine contraceptive device (placed at least 4 weeks prior to study drug administration;
condom or diaphragm + spermicide;
hormonal contraceptives (starting at least 4 weeks prior to study drug administration).

Label	URL
Approved labelling	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Confab Fasting / Confab Fed / Trillium Fasting	Confab fasting / Confab fed / Trillium fasting Group includes patients receiving once daily administration of the following Tramadol Hydrochloride (HCl) treatment: 1 x 300 mg tablet manufactured at Confab Laboratories, fasting condition in treatment period 1, 1x 300 mg tablet manufactured at Confab Laboratories, fed condition in treatment period 2, and 1 x 300 mg tablet manufactured at Trillium Healthcare Inc., fasting condition in treatment period 3.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Confab Fasting / Confab Fed / Trillium Fasting	Confab fasting / Confab fed / Trillium fasting Group includes patients receiving once daily administration of the following Tramadol Hydrochloride (HCl) treatment: 1 x 300 mg tablet manufactured at Confab Laboratories, fasting condition in treatment period 1, 1x 300 mg tablet manufactured at Confab Laboratories, fed condition in treatment period 2, and 1 x 300 mg tablet manufactured at Trillium Healthcare Inc., fasting condition in treatment period 3.
BG001	Confab Fasting / Trillium Fasting / Confab Fed	Confab fasting / Trillium fasting / Confab fed Group includes patients receiving once daily administration of the following Tramadol Hydrochloride (HCl) treatment: 1 x 300 mg tablet manufactured at Confab Laboratories, fasting condition in treatment period 1, 1 x 300 mg tablet manufactured at Trillium Healthcare Inc., fasting condition in treatment period 2, and 1x 300 mg tablet manufactured at Confab Laboratories, fed condition in treatment period 3.
BG002	Confab Fed / Confab Fasting / Trillium Fasting	Confab fed / Confab fasting / Trillium fasting Group includes patients receiving once daily administration of the following Tramadol Hydrochloride (HCl) treatment: 1x 300 mg tablet manufactured at Confab Laboratories, fed condition in treatment period 1, 1 x 300 mg tablet manufactured at Confab Laboratories, fasting condition in treatment period 2, 1 x 300 mg tablet manufactured at Trillium Healthcare Inc., fasting condition in treatment period 3.
BG003	Confab Fed / Trillium Fasting / Confab Fasting	Confab fed / Trillium fasting / Confab fasting Group includes patients receiving once daily administration of the following Tramadol Hydrochloride (HCl) treatment: 1x 300 mg tablet manufactured at Confab Laboratories, fed condition in treatment period 1, 1 x 300 mg tablet manufactured at Trillium Healthcare Inc., fasting condition in treatment period 2, and 1 x 300 mg tablet manufactured at Confab Laboratories, fasting condition in treatment period 3.
BG004	Trillium Fasting / Confab Fasting / Confab Fed	Trillium fasting / Confab fasting / Confab fed Group includes patients receiving once daily administration of the following Tramadol Hydrochloride (HCl) treatment: 1 x 300 mg tablet manufactured at Trillium Healthcare Inc., fasting condition in treatment period 1, 1 x 300 mg tablet manufactured at Confab Laboratories, fasting condition in treatment period 2, and 1x 300 mg tablet manufactured at Confab Laboratories, fed condition in treatment period 3.
BG005	Trillium Fasting / Confab Fed / Confab Fasting	Trillium fasting / Confab fasting / Confab fed Group includes patients receiving once daily administration of the following Tramadol Hydrochloride (HCl) treatment: 1 x 300 mg tablet manufactured at Trillium Healthcare Inc., fasting condition in treatment period 1, 1 x 300 mg tablet manufactured at Confab Laboratories, fed condition in treatment period 2, and 1x 300 mg tablet manufactured at Confab Laboratories, fasting condition in treatment period 3.
BG006	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG0026 BG0036 BG0046 BG0056 BG00636

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

AUC(0-t)

Area under the plasma concentration (AUC) versus time curve to the last measurable concentration.

Data from all randomized subjects who completed at least 2 periods of the study are presented.

Posted

Mean

Standard Deviation

ng.h/mL

48 hours

ID	Title	Description
OG000	1: Tramadol HCl 300 mg (Confab Laboratories) Fasting	Tramadol HCl 300 mg (Confab Laboratories) fasting Group includes the treatment period 1 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fasting / Trillium fasting / Confab fed sequences at period 1, plus the treatment period 2 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Trillium fasting / Confab fasting / Confab fed sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fed / Trillium fasting / Confab fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 3.
OG001	2: Tramadol HCl 300 mg (Confab Laboratories) Fed	Tramadol HCl 300 mg (Confab Laboratories) fed Group includes the treatment period 1 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Confab fed / Trillium fasting / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Trillium fasting / Confab fasting / Confab fed sequences at period 3.
OG002	3: Tramadol HCl 300 mg (Trillium Healthcare) Fasting	Tramadol HCl 300 mg (Trillium Healthcare) fasting Group includes the treatment period 1 data from subjects in the Trillium fasting / Confab fasting / Confab fed and Trillium fasting / Confab fed / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Confab fed / Trillium fasting / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fed / Confab fasting / Trillium fasting sequences at period 3.

Units	Counts
Participants	OG00034 OG00133 OG00233

Title

Denominators

Categories

Title	Measurements
	OG0009708± 3875 OG0019696± 3750 OG0029431± 3225

Primary

AUC(0-∞)

The area under the plasma concentration (AUC) 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

Data from all randomized subjects who completed at least 2 periods of the study are presented. The pharmacokinetic variables AUC(0-∞) of one subject for Tramadol HCl 300 mg (Confab Laboratories) fasting were not used in the analyses due to the morphology of the plasma concentration-time curves.

Posted

Mean

Standard Deviation

ng.h/mL

48 hours

ID	Title	Description
OG000	1: Tramadol HCl 300 mg (Confab Laboratories) Fasting	Tramadol HCl 300 mg (Confab Laboratories) fasting Group includes the treatment period 1 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fasting / Trillium fasting / Confab fed sequences at period 1, plus the treatment period 2 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Trillium fasting / Confab fasting / Confab fed sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fed / Trillium fasting / Confab fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 3.
OG001	2: Tramadol HCl 300 mg (Confab Laboratories) Fed	Tramadol HCl 300 mg (Confab Laboratories) fed Group includes the treatment period 1 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Confab fed / Trillium fasting / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Trillium fasting / Confab fasting / Confab fed sequences at period 3.

Primary

Cmax

Maximum plasma concentration (Cmax)

Data from all randomized subjects who completed at least 2 periods of the study are presented.

Posted

Mean

Standard Deviation

ng/mL

48 hours

ID	Title	Description
OG000	1: Tramadol HCl 300 mg (Confab Laboratories) Fasting	Tramadol HCl 300 mg (Confab Laboratories) fasting Group includes the treatment period 1 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fasting / Trillium fasting / Confab fed sequences at period 1, plus the treatment period 2 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Trillium fasting / Confab fasting / Confab fed sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fed / Trillium fasting / Confab fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 3.
OG001	2: Tramadol HCl 300 mg (Confab Laboratories) Fed	Tramadol HCl 300 mg (Confab Laboratories) fed Group includes the treatment period 1 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Confab fed / Trillium fasting / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Trillium fasting / Confab fasting / Confab fed sequences at period 3.

Secondary

Tmax

Time to maximum plasma concentration (Tmax)

Data from all randomized subjects who completed at least 2 periods of the study are presented.

Posted

Median

Full Range

hours

48 hours

ID	Title	Description
OG000	1: Tramadol HCl 300 mg (Confab Laboratories) Fasting	Tramadol HCl 300 mg (Confab Laboratories) fasting Group includes the treatment period 1 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fasting / Trillium fasting / Confab fed sequences at period 1, plus the treatment period 2 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Trillium fasting / Confab fasting / Confab fed sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fed / Trillium fasting / Confab fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 3.
OG001	2: Tramadol HCl 300 mg (Confab Laboratories) Fed	Tramadol HCl 300 mg (Confab Laboratories) fed Group includes the treatment period 1 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Confab fed / Trillium fasting / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Trillium fasting / Confab fasting / Confab fed sequences at period 3.

Secondary

t1/2

Apparent terminal elimination half-life (t1/2)

Data from all randomized subjects who completed at least 2 periods of the study are presented. The pharmacokinetic variable T1/2 of one subject for Tramadol HCl 300 mg (Confab Laboratories) fasting were not used in the analyses due to the morphology of the plasma concentration-time curves.

Posted

Mean

Standard Deviation

hours

48 hours

ID	Title	Description
OG000	1: Tramadol HCl 300 mg (Confab Laboratories) Fasting	Tramadol HCl 300 mg (Confab Laboratories) fasting Group includes the treatment period 1 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fasting / Trillium fasting / Confab fed sequences at period 1, plus the treatment period 2 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Trillium fasting / Confab fasting / Confab fed sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fed / Trillium fasting / Confab fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 3.
OG001	2: Tramadol HCl 300 mg (Confab Laboratories) Fed	Tramadol HCl 300 mg (Confab Laboratories) fed Group includes the treatment period 1 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Confab fed / Trillium fasting / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Trillium fasting / Confab fasting / Confab fed sequences at period 3.

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	1: Tramadol HCl 300 mg (Confab Laboratories) Fasting	Tramadol HCl 300 mg (Confab Laboratories) fasting Group includes the treatment period 1 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fasting / Trillium fasting / Confab fed sequences at period 1, plus the treatment period 2 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Trillium fasting / Confab fasting / Confab fed sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fed / Trillium fasting / Confab fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 3.	36	27	36
EG001	2: Tramadol HCl 300 mg (Confab Laboratories) Fed	Tramadol HCl 300 mg (Confab Laboratories) fed Group includes the treatment period 1 data from subjects in the Confab fed / Confab fasting / Trillium fasting and Confab fed / Trillium fasting / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Trillium fasting / Confab fed / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Trillium fasting / Confab fasting / Confab fed sequences at period 3.	36	27	36
EG002	3: Tramadol HCl 300 mg (Trillium Healthcare) Fasting	Tramadol HCl 300 mg (Trillium Healthcare) fasting Group includes the treatment period 1 data from subjects in the Trillium fasting / Confab fasting / Confab fed and Trillium fasting / Confab fed / Confab fasting sequences at period 1, plus the treatment period 2 data from subjects in the Confab fasting / Trillium fasting / Confab fed and Confab fed / Trillium fasting / Confab fasting sequences at period 2, and plus the treatment period 3 data from subjects in the Confab fasting / Confab fed / Trillium fasting and Confab fed / Confab fasting / Trillium fasting sequences at period 3.	36	19	36

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Difficulty to concentrate	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events2 affected36 at risk EG0020 events0 affected36 at risk
Difficulty voiding bladder	Renal and urinary disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected36 at risk EG0021 events1 affected36 at risk
Dizziness	Nervous system disorders	Non-systematic Assessment	EG00012 events12 affected36 at risk EG00113 events11 affected36 at risk EG0027 events7 affected36 at risk
Dry mouth	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events2 affected36 at risk EG0021 events1 affected36 at risk
Fatigue	General disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0011 events1 affected36 at risk EG0022 events2 affected36 at risk
Feels euphoric	Psychiatric disorders	Non-systematic Assessment	EG0004 events4 affected36 at risk EG0014 events4 affected36 at risk EG0022 events2 affected36 at risk
Feels sleepy	Nervous system disorders	Non-systematic Assessment	EG0007 events7 affected36 at risk EG0017 events7 affected36 at risk EG0026 events6 affected36 at risk
Headache	General disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0017 events7 affected36 at risk EG0023 events3 affected36 at risk
Hot flashes	Cardiac disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0016 events6 affected36 at risk EG0025 events5 affected36 at risk
Itching	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0003 events3 affected36 at risk EG0014 events4 affected36 at risk EG0021 events1 affected36 at risk
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG00011 events10 affected36 at risk EG00114 events13 affected36 at risk EG0029 events9 affected36 at risk
Stomach ache	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected36 at risk EG0012 events2 affected36 at risk EG0020 events0 affected36 at risk
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG0008 events8 affected36 at risk EG00110 events10 affected36 at risk EG0028 events8 affected36 at risk
Weakness	General disorders	Non-systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected36 at risk EG0021 events1 affected36 at risk

ID	Term
D003511	Cyclohexanols
D000441	Hexanols
D005233	Fatty Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D004123	Dimethylamines
D008744	Methylamines
D000588	Amines
D008055	Lipids