Comparative Bioavailability Study of Extended-release and Immediate-release Trazodone in Healthy Adult Volunteers

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Trazodone HCl

Registration Number: NCT00839072

Lead Sponsor: Labopharm Inc.

Brief Summary: The objective of the study is to compare the pharmacokinetic profiles of extended-release and immediate-release trazodone formulations

Detailed Description: The bioavailability of once-daily trazodone extended-release 300 mg caplets (test product) and trazodone immediate-release 100 mg tablets administered q8h (reference product) will be compared in healthy adult volunteers in a randomized, crossover fashion. Morning doses will be administered after an overnight fast. Blood samples will be collected predose and at pre-defined times over 72 hours following the morning dose. Pharmacokinetic parameters will be analyzed using ANOVA. Comparative bioavailability will be assessed on the basis of the ratio of least-squares means and/or 90% confidence interval criteria.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Availability for entire study period and willingness to adhere to protocol requirements as evidenced by signed informed consent
Male or female volunteer, aged between 18 and 45 years inclusively
BMI ≥20 and <30 kg/m2
Minimum body weight: 60 kg
Clinical laboratory values within normal range, or without clinical significance
Healthy according to medical history, clinical laboratory results and physical examination
Nonsmoker or ex-smoker

Exclusion Criteria

Significant history of hypersensitivity to trazodone or any related products, or severe hypersensitivity reactions to any drugs
Presence or history of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs or known to potentiate or predispose to undesired effects
Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease
Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric disease
Use of MAO inhibitors within 28 days of day 1 of the study
Presence of significant heart disease or disorder according to ECG
Seated systolic blood pressure lower than 90 or over 140 mmHg or diastolic blood pressure lower than 50 or over 90 mmHg at screening
Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (>3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
Any clinically significant illness in the previous 28 days before day 1 of this study
Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, and rifampin), in the previous 28 days before day 1 of this study
Females who are pregnant according to a positive serum pregnancy test, or are lactating
Females of childbearing potential who refuse to use an acceptable method of contraception from the screening visit and throughout the study
Volunteers who took an investigational product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study
Poor motivation, intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with the protocol requirements or inability to cooperate adequately, inability to understand and to observe the instructions of the physician
Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc) in the previous 56 days before day 1 of the study
Positive urine screening for drugs of abuse
Any history of tuberculosis and/or prophylaxis for tuberculosis
Positive results to HIV, HBsAg, or anti-HCV tests

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Trazodone Contramid OAD	Trazodone HCl	-
Desyrel	Trazodone HCl	-

Primary Outcome Measures

Name	Time	Method
Bioequivalence Based on Cmax	72 hours post-dose	Cmax = Maximum plasma concentration Measured in nanograms per millilitre (ng/mL)
Bioequivalence Based on AUCT	72 hours post-dose	AUCT = Area under the concentration-time curve from 0 to the time of the last quantifiable concentration
Bioequivalence Based on AUC∞	72 hours post-dose	AUC∞ = Area under the concentration-time curve extrapolated to infinity

Secondary Outcome Measures

Name	Time	Method
Time of Maximum Measured Plasma Concentration (Tmax)	72 hours post-dose
Apparent Terminal Elimination Half-Life [T½el]	72 hours post-dose	The elimination half-life (T½el) of trazodone in plasma (time it takes for the concentration of trazodone to fall to half), expressed in hours.
Area Under the Concentration-time Curve From 0 to 24 Hours [AUC0-24]	24 hours