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

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

Detailed Description
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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.

Official Title
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Crossover Comparative Bioavailability Study of Trazodone Contramid(r) OAD 300 mg Extended-release Caplets and Desyrel(r) 100 mg Immediate-release Tablets in Healthy Adult Volunteers Under Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Trazodone HCl
* Drug: Trazodone HCl


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trazodone Contramid OAD<br> | Drug: Trazodone HCl<br>* 300 mg extended-release caplet, single dose<br>* Other names: Oleptro;|
| Active Comparator: Desyrel<br> | Drug: Trazodone HCl<br>* 100 mg immediate-release tablet, dosing q8h<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioavailability, pharmacokinetics, healthy, crossover, trazodone