Phase 4
Completed N=30
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
Pharmacokinetics
Source: ClinicalTrials.gov NCT01189500 ↗
Enrolled (actual)
30
Serious AEs
1.1%
Results posted
Oct 2011
Primary outcomePrimary: 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 — 5751; 5888 ng*hr/mL
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
5751; 5888 | — |
| PRIMARY 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 |
677.7; 505.6 | — |
| SECONDARY Tamoxifen Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
70.58; 70.33 | — |
| SECONDARY Tamoxifen Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
4.00; 4.00 | — |
| SECONDARY Tamoxifen Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR |
250.5; 242.3 | — |
| SECONDARY Tamoxifen Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
115.9; 113.2 | — |
| SECONDARY Tamoxifen Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
2474; 2321 | — |
| SECONDARY Endoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
1.077; 1.226 | — |
| SECONDARY Endoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
216; 120 | — |
| SECONDARY Endoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR |
207.5; 232.5 | — |
| SECONDARY Endoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
— | — |
| SECONDARY Endoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
— | — |
| SECONDARY 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 |
8187; 9329 | — |
| SECONDARY N-desmethyl-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
18.30; 24.42 | — |
| SECONDARY N-desmethyl-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
35.9; 47.9 | — |
| SECONDARY N-desmethyl-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR |
256.0; 265.6 | — |
| SECONDARY N-desmethyl-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
— | — |
| SECONDARY N-desmethyl-tamoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
— | — |
| SECONDARY 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 |
117.5; 133.9 | — |
| SECONDARY 4-hydroxy-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
0.6716; 0.7247 | — |
| SECONDARY 4-hydroxy-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR |
6.00; 6.00 | — |
| SECONDARY 4-hydroxy-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR |
165.2; 177.0 | — |
| SECONDARY 4-hydroxy-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
— | — |
| SECONDARY 4-hydroxy-tamoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR |
— | — |
| SECONDARY Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR |
NA; 1.300; 1.875; 4.650; 11.45; 13.90 | — |
| SECONDARY Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR |
NA; 0.2900; NA; 0.3370; NA; 0.3430 | — |
| SECONDARY Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR |
NA; 3.600; 0.0000; 4.120; 0.8050; 5.650 | — |
| SECONDARY Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR |
NA; 0.0000; NA; 0.0000; NA; 0.0000 | — |
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
Data sourced from ClinicalTrials.gov (NCT01189500). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.