Study of Two Tramadol Contramid® OAD 300 mg Controlled-Release Tablets From Two Different Manufacturing Sites Following a 300 mg Dose in Healthy Subjects Under Fasting and Fed Conditions
Condition: Healthy
Intervention: Tramadol hydrochloride; Tramadol HCl; Tramadol HCl
Intervention description: 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.; 1x300mg Tramadol Hydrochloride (HCl) tablet (Confab Laboratories), fed 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.; 1x300mg Tramadol Hydrochloride (HCl) tablet (Trillium Healthcare) 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.
Intervention MeSH terms: Tramadol
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy Subjects

Summary:

      The objective of this study is to compare the rate and extent of absorption of two Tramadol
      Contramid® OAD 300 mg controlled-release tablets from two different manufacturing sites,
      administered as 1 x 300 mg controlled-release tablet under fasting conditions. The effect of
      food on the to-be-marketed formulation was also assessed.
    

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).