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)

A Randomized, Two-way Crossover Study to Compare the Bioavailability of 300 mg Trazodone Hydrochloride Extended-release Caplets (Containing Contramid®) (Administered as a Single Dose) and 100 mg Trazodone Hydrochloride Immediate-release Tablets (Administered Three Times Daily) Under Fasting Conditions

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Trazodone HCl; Drug: Trazodone HCl

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trazodone HCl OAD; OAD: Once A Day	Drug: Trazodone HCl; 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.; Other Names: Oleptro; Drug: Trazodone HCl; 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.
Active Comparator: Trazodone HCl (Apotex Corp.)	Drug: Trazodone HCl; 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.; Other Names: Oleptro; Drug: Trazodone HCl; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioequivalence Based Cmax	Cmax = Maximum plasma concentration. Measured in nanogram per milliliter (ng/mL).	68 hours
Bioequivalence Based on AUC(0-tlast)	AUC(0-tlast) = Area under the plasma concentration curve (AUC) vs (versus) time data pairs, where tlast is the time of the last quantifiable concentration. Measured in nanogram x hours per milliliter (ng*h/mL).	68 hours
Bioequivalence Based on AUC(0-∞)	AUC(0-∞) = Area under the plasma concentration curve vs time data pairs, with extrapolation to infinity (∞). Measured in nanogram x hours per milliliter (ng*h/mL).	68 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration vs. Time Data Pairs, for the First 24 Hours [AUC(0-24)]		24 hours
Time to Maximum Plasma Concentration (Tmax)		68 hours
Apparent Terminal Elimination Rate Constant (λz)	The elimination rate constant of trazodone (Lamda z). It is the ratio of clearance to volume of distribution and is expressed in units of 1/hour. This constant is used in half-life calculations.	68 hours
Apparent Terminal Half-life (t½.z)	The elimination half-life (T½z) of trazodone in plasma (time it takes for the concentration of trazodone to fall to half), expressed in hours.	68 hours

Collaborators and Investigators

• Sponsor: Labopharm Inc.

Publications and helpful links

Helpful Links

• Approved Labelling

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: May 10, 2010
• First Submitted That Met QC Criteria: May 11, 2010
• First Posted (Estimate): May 12, 2010

Study Record Updates

• Last Update Posted (Estimate): April 27, 2012
• Last Update Submitted That Met QC Criteria: April 24, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Healthy subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Trazodone
• Other Study ID Numbers: 04ACL1-010