Study Evaluating the Potential of DVS SR to Inhibit the CYP2D6 Pathway

Study Overview
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Brief Summary
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To evaluate the effects of multiple oral doses of desvenlafaxine sustained release (DVS SR) and paroxetine on the biotransformation of codeine to morphine in healthy subjects. To assess the safety and tolerability of DVS SR and paroxetine when coadministered with codeine to healthy subjects.

Detailed Description
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This is a randomized, open-label, inpatient/outpatient, 3-period crossover study in healthy subjects.The study will consist of 3 treatment periods. In treatment period 1, subjects will be randomly assigned on study day 1. A single 60-mg dose of codeine will be administered to all subjects. In periods 2 and 3, subjects will receive either DVS SR 100 mg/day or paroxetine 20 mg/day until the steady state is reached. At steady state, subjects will receive codeine 60 mg concomitantly with either DVS SR 100 mg or paroxetine 20 mg, depending on the treatment sequence to which they are assigned. DVS SR 100 mg or paroxetine 20 mg administration will continue for an additional 2 days. In treatment period 3, subjects will receive the alternative treatment sequence.

Official Title
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A Randomized, Open-Label, 3-Period Crossover Study to Evaluate the Effect of Multiple Doses of DVS SR and Paroxetine on the CYP2D6 Biotransformation of Codeine to Morphine in Healthy Subjects.

Conditions
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Depressive Disorder, Major, Diabetic Neuropathies, Fibromyalgia, Vasomotor Symptoms

Intervention / Treatment
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* Drug: desvenlafaxine sustained release (DVS SR)
* Drug: Paroxetine
* Drug: Codeine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy men and nonlactating and nonpregnant women of nonchildbearing potential aged from 18 to 45 years. Body mass index in the range of 18 to 30 kg/m2 and body weight ≥50 kg. Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Exclusion criteria: History of bronchial asthma, of seizure disorder (other than a single childhood febrile seizure)and of any clinically important drug allergy and any known allergy to desvenlafaxine, venlafaxine, paroxetine, codeine, or any of the non-active excipients in the dosage forms. Use of any CYP2D6 inhibitors or inducers within 30 days before test article administration. Demonstration of a positive orthostatic test at screening.

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

Sexes Eligible for Study
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Male

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

| Intervention/Treatment |
| --- |
|Drug: desvenlafaxine sustained release (DVS SR)|nan|
|Drug: Paroxetine|nan|
|Drug: Codeine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the biotransformation of codeine to morphine and the safety and tolerability of DVS SR |  |  |