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

NCT01189500 | Completed Phase 4 Results

• 2 other identifiers: B20610273151A1-1206
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Pharmacokinetics

Keywords

Pharmacokinetic; safety and tolerability; genetic testing; CYP 2D6

Outcome Measures

Primary Outcomes (2)

• 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

  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, 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.

• 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

  Endoxifen is a metabolite of Tamoxifen. 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, 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 (26)

• Tamoxifen Maximum Observed Concentration (Cmax) Following Tamoxifen 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, 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.

• Tamoxifen Time for Cmax (Tmax) Following Tamoxifen 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, 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.

• Tamoxifen Terminal Half-life (t 1/2) Following Tamoxifen 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, 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.

• Tamoxifen Apparent Clearance (CL/F) Following Tamoxifen 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, 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.

• Tamoxifen Apparent Volume of Distribution (Vz/F) Following Tamoxifen 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, 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.

Study Arms (1)

Tamoxifen and Desvenlafaxine SR

EXPERIMENTAL

Drug: Tamoxifen; Drug: Tamoxifen and Desvenlafaxine Succinate Sustained Release

Interventions

Tamoxifen DRUG

Period 1-Tamoxifen 40mg on study day 1.

Tamoxifen and Desvenlafaxine SR

Tamoxifen and Desvenlafaxine Succinate Sustained Release DRUG

Period 2-Desvenlafaxine SR 100mg on days 1-28 with coadministration of Tamoxifen 40mg on day 7.

Tamoxifen and Desvenlafaxine SR

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Pfizer Investigational Site

Miami, Florida, 33126, United States

Location

Pfizer Investigational Site

Miami, Florida, 33134, United States

Location

Related Publications (1)

• 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.

  PMID: 25138680 DERIVED

MeSH Terms

Interventions

Tamoxifen

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 26, 2010
• Study Start: August 1, 2010
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: November 7, 2011
• Results First Posted: October 17, 2011

Record last verified: 2011-11

Locations

US (2)