A Study to Compare the Bioavailability of 300 mg Trazodone Hydrochloride Extended-release Caplets and 100 mg Trazodone Hydrochloride Immediate-release Tablets (Administered Three Times Daily)
Condition: Healthy
Intervention: Trazodone HCl; Trazodone HCl
Intervention description: Dosage form: Extended-release caplets containing 300 mg trazodone HCl
Dose: 300 mg trazodone HCl extended-release caplets (one caplet) at 23:30 on Day 1 of the test product treatment period following a fasting period of at least 4 hours.; Dosage form: Immediate-release tablets containing 100 mg trazodone HCl
Dose: 100 mg trazodone HCl immediate-release tablets (one tablet per dosing time) at 23:30 on Day 1, at 07:30 and 15:30 on Day 2 of the reference product treatment period.
Intervention MeSH terms: Trazodone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy subjects

Summary:

      The objective of this study was to compare the pharmacokinetic profiles of the test product,
      300 mg trazodone hydrochloride (HCl) extended-release caplets (containing Contramid®), when
      administered as a single dose, and the reference product, 100 mg trazodone HCl
      immediate-release tablets (Apotex Corp), when administered three times daily. For this
      purpose the rate and extent of absorption of trazodone and formation of
      m-chlorophenylpiperazine (mCPP) after administration of the two formulations, were compared
      under fasting conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy male and female subjects 18 to < 56 years of age.

          -  Body mass within 10% of the ideal mass in relation to height and age, according to
             Body Mass Index.

          -  Body mass not less than 53 kg.

          -  Findings within the range of clinical acceptability in medical history and physical
             examination, and laboratory results within the laboratory reference ranges for the
             relevant laboratory tests (unless the investigator considered the deviation to be
             irrelevant for the purpose of the study).

          -  Normal 12-lead 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- and post-study physical examination and laboratory
             investigations.

          -  Ability to comprehend and willingness to sign both statements of informed consent (for
             screening and period-related procedures).

          -  Non-smoker or past smoker who stopped the use of any form of tobacco, including snuff
             or similar products, at least 3 months before entering the study.

          -  For females, the following conditions had to be met:

               1. Had been surgically sterilized or undergone a hysterectomy, or

               2. Was of childbearing potential, and all of the following conditions were met:

                    1. Had a negative pregnancy test at screening. If this test was positive, the
                       subject was to be excluded from the study before receiving study medication.
                       In the rare circumstance that a pregnancy was discovered after the subjects
                       received the study medication, every attempt was to be made to follow such
                       subjects to term.

                    2. Had to agree to use an accepted method of contraception (i.e., spermicide
                       and barrier methods or spermicide and non-hormonal intrauterine
                       contraceptive device). The subject had to agree to continue with the same
                       method throughout the study. Hormonal contraceptives were not allowed.

               3. Females not of childbearing potential could also have been included if they had
                  no menstrual period for one year and were considered as post-menopausal.

        Exclusion Criteria:

          -  Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional
             or intellectual problems likely to have limited the validity of consent to participate
             in the study or to have limited 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 investigator. Hormonal contraceptive agents
             were not allowed.

          -  Participation in another study with an experimental drug, where the last
             administration (of previous study medication) was 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.

          -  A major illness during the 3 months before commencement of the screening period.

          -  History of hypersensitivity to the study medication or any related medication.

          -  History of bronchial asthma.

          -  History of epilepsy.

          -  History of porphyria.

          -  Relevant history or laboratory or clinical findings indicative of acute or chronic
             disease, likely to have influenced the 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 < 40 beats per minute during the screening
             period, either supine or standing.

          -  Positive testing for HIV and/or Hepatitis B and/or Hepatitis C.

          -  Positive urine screen for drugs of abuse.

          -  Positive urine screen for tobacco use.

          -  A serum pregnancy test (beta human chorionic gonadotropin [β-HCG]) either positive or
             not performed or lactation.