A Dose Linearity Study of the Labopharm Formulation of Tramadol HCl/Contramid®, 100 mg, 200 mg and 300 mg After A Single Oral Administration In Fasting Condition, In Healthy Human Volunteers
Condition: Healthy
Intervention: Tramadol HCl
Intervention description: One single oral administration of Tramadol HCl 100 mg, 200 mg or 300 mg as per randomization schedule.
Intervention MeSH terms: Tramadol
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy volunteers

Summary:

      The purposes of this study were:

        -  To evaluate the plasma pharmacokinetic profile of tramadol and its principal metabolite,
           the O-desmethyltramadol, after a single oral administration of 100, 200 and 300 mg of
           tramadol as the Labopharm extended-release formulation prepared with Contramid.

        -  To assess the dose linearity of tramadol and its principal metabolite, the
           O-desmethyltramadol, between 100 mg and 300 mg following a single dose administration of
           the Labopharm extended-release formulation prepared with Contramid under fasting
           conditions in young healthy volunteers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Availability of subject for the entire study period and willingness to adhere to
             protocol requirements as evidenced by the informed consent form duly signed by the
             subject.

          -  Males aged from 18 to 45 years inclusively and with Body Mass Index (BMI) between 18
             and 30 kg/m2 inclusively.

          -  Clinical laboratory values within 10% above or below the laboratory's stated normal
             range; if not within this range, the clinical investigator will decide if they were
             not clinically significant and recorded this fact on the Case Report Form (CRF).

          -  Healthy according to the physical examination and laboratory results.

          -  Normal cardiovascular function according to a 12-lead electrocardiogram (ECG).

          -  Non-smoker or subjects smoking no more than 5 cigarettes per day (or equivalent) and
             able to abstain from smoking during inpatient phases of the study.

          -  Subjects covered by Social Security in compliance with the recommendations of French
             Law relating to biomedical research.

          -  Subjects with normal dietary requirements (neither vegetarian, nor on a diet).

        Exclusion Criteria:

          -  History of hypersensitivity to tramadol or any other compounds.

          -  Presence or significant history of gastrointestinal, liver or kidney disease, or any
             other conditions known to interfere with the absorption, distribution, metabolism or
             excretion of drugs.

          -  Presence or significant history of cardiovascular, pulmonary, haematological,
             neoplasic, neurological, psychiatric, endocrine, immunological or dermatological
             disease.

          -  Presence or significant history of glaucoma.

          -  Supine pulse rate lower than 45 beats per minute (bpm) after 5 minutes at rest or
             higher than 100 bpm.

          -  History of hypotensive episodes or a standing systolic blood pressure reading of <100
             mmHg or a diastolic reading of <45 mmHg, measured on the screening day.

          -  History of hypertensive episodes or a supine systolic blood pressure reading of >145
             mmHg or a diastolic reading of >95 mmHg, measured on the screening day.

          -  Presence of atrioventricular (AV) block assessed during pre-study evaluation or during
             the study. The lower limit considered for a first degree AV block was be a PR interval
             of 200 millisecond (msec).

          -  Maintenance therapy with any drug, or history of drug dependency, alcohol abuse (>3
             units of alcohol per day), or serious psychological disease.

          -  Subjects consuming large quantities of drinks containing xanthine bases (coffee, tea,
             chocolate or cola; more than 6 cups or glasses per day).

          -  Any clinically significant illness in the previous 21 days before day 1 of this study.

          -  Subjects who had undergone general anesthesia within 3 months prior to the present
             study.

          -  Use of drugs known to affect liver enzymes (eg, inducers or inhibitors of Cytochrome
             P450) in the previous 30 days before day 1 of this study (eg, all barbiturates,
             corticosteroids, di & methyl-phenylhydantoin).

          -  Use of any medication (including OTC preparations) in the previous 14 days before day
             1 of this study.

          -  Donation of 350 mL (or more) of blood in the previous 3 months or participation in
             another clinical trial in the previous 3 months before day 1 of this study.

          -  Subjects undergoing dental care.

          -  Positive urine drug screening.

          -  Positive results to human immunodeficiency virus (HIV) 1 & 2 or hepatitis B surface
             antigen (HBsAg) or anti-HCV (hepatitis C virus) tests.

          -  History of fainting upon blood sampling.

          -  Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional
             or intellectual problems likely to limit the validity of the consent to participate in
             the study or to limit the ability to comply with the protocol requirements.

          -  Subjects unable to abstain from intensive muscular effort or sport competitions during
             the week prior to the study and throughout the study itself.

          -  Subjects who had forfeited his freedom by administrative or legal award or who were
             under guardianship.

          -  Subjects who received the ceiling amount of 25,000 francs within the last 12 months or
             who reached this ceiling with the payment of this allowance for this study.