Study Evaluating the Effect of Desvenlafaxine on the Pharmacokinetics of Midazolam

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the effect of desvenlafaxine administered as DVS SR on the pharmacokinetics of midazolam in healthy male and female subjects. The amount of drug in the body and the effect of the drug will also be evaluated.

Official Title
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An Open-Label, Two-Period, Sequential Drug Interaction Study to Evaluate the Effect of Multiple Doses of Desvenlafaxine Succinate Sustained Release (DVS SR) on the Pharmacokinetics of Midazolam When Coadministered in Healthy Subjects

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Desvenlafaxine Succinate Sustained Release
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or non-pregnant, non-lactating women, 18 to 55 years of age inclusive at screening. Healthy as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG). Nonsmoker or smoker of fewer than 10 cigarettes per day as determined by history. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 Ilbs). Exclusion Criteria: Presence or history of any significant cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease. Presence or history of glaucoma or intraocular pressure. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational product. Allergy to midazolam, other benzodiazepine, desvenlafaxine, or venlafaxine. Acute disease state (eg, nausea, vomiting, fever, or diarrhea) with 7 days before study day 1. Admitted alcohol abuse or history of alcohol use that may interfere with the subject's ability to comply with the protocol requirements. History of drug abuse within 1 year before study day 1.

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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DVS SR<br> | Drug: Desvenlafaxine Succinate Sustained Release<br>* 50 mg DVS SR tablet days 1-6, period 2 only.<br>Drug: Midazolam<br>* 4 mg midazolam (2 mL midazolam syrup) day 1, period 1 and day 6, period 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midazolam Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR | AUCinf measured as nanograms multiplied by hours divided by milliliters (ng*hr/mL). | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR | Cmax measured as nanograms per milliliters (ng/mL). | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| 1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR | 1-Hydroxy-Midazolam is an analyte of Midazolam. | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| 1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR |  | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midazolam Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR |  | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR |  | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR |  | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| 1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR |  | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| 1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR |  | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 
| 1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR |  | Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression