Study Evaluating the Effect of Desvenlafaxine on the Pharmacokinetics of Midazolam

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Desvenlafaxine Succinate Sustained Release; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: August 3, 2009
• First Submitted That Met QC Criteria: August 4, 2009
• First Posted (ESTIMATE): August 6, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 15, 2011
• Last Update Submitted That Met QC Criteria: August 9, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: depression
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Midazolam; Desvenlafaxine Succinate
• Other Study ID Numbers: 3151A1-1205; B2061001