Clinical trial NCT01189500: Open-Label Drug Interaction Study Evaluating Desvenlafaxine Succinate Sustained Release (DVS SR) 100mg On The Pharmacokinetics Of Tamoxifen When Coadministered To Healthy Post-Menopausal Female Subjects
Official title: 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 Tamoxifen When Co-Administered In Healthy Post-Menopausal Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pharmacokinetics
Keywords: Pharmacokinetic
safety and tolerability
genetic testing
CYP 2D6
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-08-26
Enrollment: 30
Sex: FEMALE
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this study is to evaluate the effect of multiple doses of Desvenlafaxine SR on the pharmacokinetics of Tamoxifen and endoxifen when coadministered to healthy post-menopausal female subjects. This study will also evaluate the safety and tolerability of Desvenlafaxine SR and Tamoxifen when coadministered to healthy post-menopausal female subjects.


Eligibility criteria: Inclusion Criteria:

* Healthy post-menopausal female subjects, at least 45 years of age, with confirmed post-menopausal status
* Hysterectomized subjects
* Body Mass Index (BMI) less than or equal to 34.0 kg/m2
* 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
* Presence or history of deep vein thrombosis or transient ischemic attack
* History of seizure disorder
* Presence or history of glaucoma or increased intraocular pressure
* Allergy to or unable to tolerate tamoxifen, 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
* Use of CYP 2D6 inhibitors and CYP 3A4 inhibitors/inducers

Primary outcomes:
measure: Tamoxifen Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Endoxifen (Metabolite) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Endoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
Secondary outcomes:
measure: Tamoxifen Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Tamoxifen Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Tamoxifen Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Tamoxifen Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Tamoxifen Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Endoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Endoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Endoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Endoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Endoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: N-desmethyl-tamoxifen (Metabolite) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: N-desmethyl-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: N-desmethyl-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: N-desmethyl-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: N-desmethyl-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: N-desmethyl-tamoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: 4-hydroxy-tamoxifen (Metabolite) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: 4-hydroxy-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: 4-hydroxy-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: 4-hydroxy-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: 4-hydroxy-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: 4-hydroxy-tamoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: Period 1 / Day 1: 0, 0.5, 1, 2, 3, 4, 6, 8, 12,16, 24, 48, 72, 120, 168, 216, 264, 312, 384, 456, and 528 hours after dosing; Period 2 / Day 1 and Day 7: 0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours; 0 hour on Day 8, 9, 10, 12, 14, 16, 18, 20, 23, 26 and 29.
measure: Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: 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, 312, 384, 456, and 528 hours after dosing
measure: Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: 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, 312, 384, 456, and 528 hours after dosing
measure: Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: 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, 312, 384, 456, and 528 hours after dosing
measure: Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
timeFrame: 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, 312, 384, 456, and 528 hours after dosing
Other outcomes:
Locations:
city: Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Nichols AI, Lubaczewski S, Liang Y, Matschke K, Braley G, Ramey T. Open-label, 2-period sequential drug interaction study to evaluate the effect of a 100-mg dose of desvenlafaxine on the pharmacokinetics of tamoxifen when coadministered in healthy postmenopausal female subjects. Int J Clin Pharmacol Ther. 2014 Oct;52(10):830-41. doi: 10.5414/CP201958.