Open Label Drug Interaction Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) 100mg On The Pharmacokinetics Of Aripiprazole When Coadministered To Healthy Subjects

An Open-Label, 2-Period Sequential Drug Interaction Study To Evaluate The Effect Of A 100 Mg Dose Of Desvenlafaxine SR On The Pharmacokinetics Of Aripiprazole When Coadministered In Healthy Subjects

The goal of this study is to evaluate the effect of multiple doses of Desvenlafaxine Sustained Release (SR) on the pharmacokinetics of Aripiprazole when coadministered to healthy adult subjects. This study will also evaluate the safety and tolerability of Desvenlafaxine SR and Aripiprazole when coadministered to healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Cytochrome P-450 CYP2D6; CYP3A4 Protein, Human
• Intervention / Treatment: Drug: Aripiprazole; Drug: Aripiprazole + desvenlafaxine succinate sustained release

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33134
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 18 and 55 years
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight >50 kg (110 lbs)
• Nonsmoker or smoker of fewer than 5 cigarettes per day as determined by history
• An informed consent document signed and dated by the subject

Exclusion Criteria:

• History of significant blood, kidney, endocrine, lung, gastrointestinal, heart, liver, psychiatric, neurologic, or allergic disease
• History of seizure disorder
• Presence or history of glaucoma or increased intraocular pressure
• Allergy to or unable to tolerate aripiprazole, desvenlafaxine, or venlafaxine
• History of substance abuse within 1 year of study
• A positive urine drug screen
• Treatment with an investigational drug within 30 days
• Consumption of grapefruit or grapefruit related citrus fruits
• 12 lead ECG demonstrating QTc >450 msec at screening
• Pregnant or nursing females
• Use of prescription or nonprescription drugs and dietary supplements
• History of sensitivity to heparin or heparin induced thrombocytopenia
• Severe acute or chronic medical or psychiatric condition or laboratory abnormality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aripiprazole + Desvenlafaxine SR	Drug: Aripiprazole; Period 1-Aripiprazole 5mg on study day 1.; Other Names: DVS-233; Pristiq; Drug: Aripiprazole + desvenlafaxine succinate sustained release; Period 2-Desvenlafaxine SR 100mg on days 1-19 with coadministration of Aripiprazole 5mg on day 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aripiprazole Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SR	Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞); measured as nanograms multiplied by hours divided by milliliters (ng*hr/mL).	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aripiprazole Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR	Cmax measured as nanograms per milliliters (ng/mL).	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Aripiprazole Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR	Time for maximum observed plasma concentration.	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Aripiprazole Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR	Terminal half-life is the time measured for the plasma concentration to decrease by one half.	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Aripiprazole Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SR	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood calculated as (Dose/AUCinf); measured as milliliters per minute (mL/min).	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Aripiprazole Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SR	Calculated as Dose / (AUCinf * kel); where kel=terminal phase rate constant.	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Dehydro-aripiprazole (Metabolite) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Aripiprazole Alone and When Coadministered With DVS SR	Dehydro-aripiprazole is a metabolite of Aripiprazole. Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Dehydro-aripiprazole (Metabolite) Maximum Observed Plasma Concentration (Cmax) Following Aripiprazole Alone and When Coadministered With DVS SR		Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing
Dehydro-aripiprazole (Metabolite) Time for Cmax (Tmax) Following Aripiprazole Alone and When Coadministered With DVS SR	Time for maximum observed plasma concentration.	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Dehydro-aripiprazole (Metabolite) Terminal Half-life (t 1/2) Following Aripiprazole Alone and When Coadministered With DVS SR	Terminal half-life is the time measured for the plasma concentration to decrease by one half.	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Dehydro-aripiprazole (Metabolite) Apparent Clearance (CL/F) Following Aripiprazole Alone and When Coadministered With DVS SR	Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood calculated as (Dose/AUCinf).	Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Dehydro-aripiprazole (Metabolite) Apparent Volume of Distribution (Vz/F) Following Aripiprazole Alone and When Coadministered With DVS SR		Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing; Period 2 / Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours after dosing; also 0 hour Period 2 / Day 8, 9, 10, 12, 14, 16, 18, and Day 20
Plasma Aripiprazole Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg + Aripiprazole 5 mg	Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.	Period 1 / Day 1 and Period 2 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after dosing
Plasma Dehydro-aripiprazole (Metabolite) Concentration Versus Time Summary: Aripiprazole 5mg, DVS SR 100 mg, Aripiprazole 5 mg	Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.100 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.	Period 1 / Day 1 and Period 2 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 120, 168, 216, 264, and 312 hours after 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: August 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: August 24, 2010
• First Submitted That Met QC Criteria: August 24, 2010
• First Posted (Estimate): August 25, 2010

Study Record Updates

• Last Update Posted (Estimate): November 6, 2011
• Last Update Submitted That Met QC Criteria: November 1, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: genetic testing; Pharmacokinetic; safety and tolerability; CYP 2D6 and CYP 3A4
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Serotonin and Noradrenaline Reuptake Inhibitors; Aripiprazole; Desvenlafaxine Succinate
• Other Study ID Numbers: B2061026; 3151A1-1207