A Study to Compare the Relative Bioavailability of Two 200 Mg Tramadol Hydrochloride Tablet Products Under Fasting Conditions

• Sponsor: Labopharm Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834366
• Collaborator: (none)
• Enrollment: 26
• Arms: 2
• Duration (Days): 28

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Tramadol HCl	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Mar 1, 2005
• Actual Study Completion Date: Mar 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Tramadol 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.
Experimental: Tramadol HCl 200 mg Uncoated Tablets Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.	Drug: Tramadol 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.

Outcome Measures

Primary Outcome Measures

1. AUC(0-t) [48 hours]

   Area under plasma concentration versus time curve to the last measurable concentration. Unit is ng.h/mL. h=hours.

2. AUC(0-Inf) [48 hours]

   Area under plasma concentration versus time curve extrapolated to infinity. Unit is ng.h/mL. h=hour.

3. Cmax [48 hours]

   Maximum plasma concentration

Secondary Outcome Measures

1. Tmax [48 hours]

   Time to the maximum concentration

2. t1/2 [48 hours]

   Apparent terminal elimination half-life

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Labopharm Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Approved labelling

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834366
• Other Study ID Numbers: MDT1-013
• First Posted: Feb 3, 2009
• Last Update Posted: Apr 30, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by , ,: Healthy volunteers
• Additional relevant MeSH terms: Tramadol

Study Results

Participant Flow

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets	Tramadol HCl 200 mg Uncoated Tablets
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.
Period Title: Treatment Period 1
STARTED	13	13
COMPLETED	12	12
NOT COMPLETED	1	1
Period Title: Treatment Period 1
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets	Tramadol HCl 200 mg Uncoated Tablets	Total
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0.0 0%
Between 18 and 65 years	13 100%	13 100%	26.0 100%
>=65 years	0 0%	0 0%	0.0 0%
Sex: Female, Male (Count of Participants)
Female	6 46.2%	5 38.5%	11.0 42.3%
Male	7 53.8%	8 61.5%	15.0 57.7%

Outcome Measures

1. Primary Outcome

Title	AUC(0-t)
Description	Area under plasma concentration versus time curve to the last measurable concentration. Unit is ng.h/mL. h=hours.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets	Tramadol HCl 200 mg Uncoated Tablets
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.
Measure Participants	12	12
Mean (Standard Deviation) [ng.h/mL]	5181 (1338)	5010 (1176)

2. Secondary Outcome

Title	Tmax
Description	Time to the maximum concentration
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets	Tramadol HCl 200 mg Uncoated Tablets
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.
Measure Participants	12	12
Median (Full Range) [hours]	6	6

3. Primary Outcome

Title	AUC(0-Inf)
Description	Area under plasma concentration versus time curve extrapolated to infinity. Unit is ng.h/mL. h=hour.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets	Tramadol HCl 200 mg Uncoated Tablets
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.
Measure Participants	12	12
Mean (Standard Deviation) [ng.h/mL]	5328 (1421)	5175 (1241)

4. Primary Outcome

Title	Cmax
Description	Maximum plasma concentration
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets	Tramadol HCl 200 mg Uncoated Tablets
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.
Measure Participants	12	12
Mean (Standard Deviation) [ng/mL]	218 (49)	209 (45)

5. Secondary Outcome

Title	t1/2
Description	Apparent terminal elimination half-life
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets	Tramadol HCl 200 mg Uncoated Tablets
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.
Measure Participants	12	12
Mean (Standard Deviation) [hours]	7.08 (1.45)	7.38 (1.76)

Adverse Events

Arm/Group Title	Tramadol HCl 200 mg Film-coated Tablets		Tramadol HCl 200 mg Uncoated Tablets
Arm/Group Description	Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Film-coated Tablet based on randomization schedule.		Single oral administration in fasting conditions of 1x200mg Tramadol HCl 200 mg Uncoated Tablet based on randomization schedule.
All Cause Mortality
	Tramadol HCl 200 mg Film-coated Tablets		Tramadol HCl 200 mg Uncoated Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tramadol HCl 200 mg Film-coated Tablets		Tramadol HCl 200 mg Uncoated Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Tramadol HCl 200 mg Film-coated Tablets		Tramadol HCl 200 mg Uncoated Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/25 (36%)		10/25 (40%)
Gastrointestinal disorders
Nausea	4/25 (16%)	4	1/25 (4%)	2
Nervous system disorders
Drowsiness	1/25 (4%)	1	5/25 (20%)	5
Dizziness	7/25 (28%)	9	6/25 (24%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a publication based on the results of this study is envisaged, approval from the sponsor will be obtained and a draft manuscript will be submitted to the sponsor for scrutiny and comment.