Study Evaluating the Effect of Desvenlafaxine on the Pharmacokinetics of Midazolam

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00952653
First received: August 3, 2009
Last updated: August 9, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Desvenlafaxine Succinate Sustained Release
Drug: Midazolam
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    AUCinf measured as nanograms multiplied by hours divided by milliliters (ng*hr/mL).

  • Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Cmax measured as nanograms per milliliters (ng/mL).

  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    1-Hydroxy-Midazolam is an analyte of Midazolam.

  • 1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: June 2010
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00952653

Locations
United States, Connecticut
Pfizer Investigational Site
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc
ClinicalTrials.gov Identifier: NCT00952653     History of Changes
Other Study ID Numbers: 3151A1-1205, B2061001
Study First Received: August 3, 2009
Results First Received: July 6, 2011
Last Updated: August 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
depression

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Midazolam
O-desmethylvenlafaxine
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Antidepressive Agents

ClinicalTrials.gov processed this record on July 22, 2014