Study Evaluating the Pharmacokinetics of Venlafaxine Extended-Release (ER) and Desvenlafaxine Succinate Sustained-Release (DVS SR) 50 mg in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine if the relative difference in Pharmacokinetics (PK) between extensive metabolizers (EMs) and poor metabolizers (PMs) is the same with desvenlafaxine SR and venlafaxine ER when a single dose is administered.

Official Title
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A Randomized, Open-Label, Two-Period, Parallel Group, Crossover Study to Evaluate the Pharmacokinetics of Venlafaxine Extended-Release and DVS SR in Healthy Subjects Who Are Extensive or Poor Cytochrome P450 2D6 Substrate Metabolizers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)
* Drug: Venlafaxine Extended Release (VEN ER)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women aged 18 to 55 years. Healthy as determined by the investigator on the basis of medical history and physical examination, laboratory test results, vital signs, and 12-lead electrocardiogram (ECG). History of being a nonsmoker for at least 1 year. Subjects have to be either extensive CYP2D6 metabolizers with a normal complement of 1 or 2 fully active enzyme gene alleles or poor CYP2D6 metabolizers (lack of active enzyme gene alleles) via genetic testing of a blood sample. Exclusion Criteria: Presence or history of any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease or any severe conditions of the ears, eyes or throat (such as glaucoma or increased intraocular pressure). Known or suspected alcohol abuse or consumption of more than 2 standard units per day (a standard unit equals 12 ounces of beer, 1½ ounces of 80-proof alcohol, or 6 ounces of wine) within the past 6 months. Known or suspected current abuse of prohibited drugs or other substances. Use of any hormonal therapy within 30 days before study day -1 until the end of the partial inpatient confinement period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DVS/VEN<br> | Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)<br> <br> Drug: Venlafaxine Extended Release (VEN ER)<br> <br> |
| Active Comparator: VEN/DVS<br> | Drug: Desvenlafaxine Succinate Sustained-Release (DVS SR)<br> <br> Drug: Venlafaxine Extended Release (VEN ER)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) of Venlafaxine After Single Dose of Venlafaxine Extended-release (VEN ER) by Metabolizer Status | Cmax is a measure of drug metabolism and presented as least squares geometric mean with 90% Confidence Interval. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers. | single dose | 
| Area Under the Concentration-time Curve (AUC) of Venlafaxine After Single Dose of VEN ER by Metabolizer Status | AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers. | single dose | 
| Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status | Cmax is a measure of drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers. | single dose | 
| Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of VEN ER by Metabolizer Status | AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers. | single dose | 
| Maximum Concentration (Cmax) of Desvenlafaxine After Single Dose of Desvenlafaxine Succinate Sustained-Release (DVS SR) by Metabolizer Status | Cmax is a measure of drug metabolism and is presented as least squares geometric mean with 90% Confidence Interval.Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), and ultrarapid (UM) metabolizers. | single dose | 
| Area Under the Concentration-time Curve (AUC) of Desvenlafaxine After Single Dose of DVS SR by Metabolizer Status | AUC is drug level over time and measures drug metabolism. Variations in drug metabolism among individuals can be due to differences in genetic expression (phenotype) of Cytochrome P450 (CYP450) enzymes. Enzyme CYP2D6 has 4 metabolizer phenotypes: poor (PM), intermediate (IM), extensive (EM), ultrarapid (UM) metabolizers. | single dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Subjects