Pharmacokinetics
Conditions
Keywords
Pharmacokinetic, safety and tolerability, genetic testing, CYP 2D6
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.
Interventions
DRUGTamoxifen
Period 1-Tamoxifen 40mg on study day 1.
DRUGTamoxifen and Desvenlafaxine Succinate Sustained Release
Period 2-Desvenlafaxine SR 100mg on days 1-28 with coadministration of Tamoxifen 40mg on day 7.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
45 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. | 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). |
| 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 | 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 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 - ∞). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Terminal half-life is the time measured for the plasma concentration to decrease by one half. |
| 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. | 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). |
| 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. | Calculated as Dose / (AUCinf \* kel); where kel=terminal phase rate constant. |
| Endoxifen (Metabolite) 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. | — |
| Endoxifen (Metabolite) 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. | Time for maximum observed plasma concentration. |
| Endoxifen (Metabolite) 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. | Terminal half-life is the time measured for the plasma concentration to decrease by one half. |
| Endoxifen (Metabolite) 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. | 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). |
| Endoxifen (Metabolite) 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. | — |
| 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 | 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. | N-desmethyl-tamoxifen 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 - ∞). |
| N-desmethyl-tamoxifen (Metabolite) 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. | — |
| N-desmethyl-tamoxifen (Metabolite) 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. | Time for maximum observed plasma concentration. |
| N-desmethyl-tamoxifen (Metabolite) 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. | Terminal half-life is the time measured for the plasma concentration to decrease by one half. |
| 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. | Cmax measured as nanograms per milliliters (ng/mL). |
| N-desmethyl-tamoxifen (Metabolite) 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. | — |
| 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 | 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. | 4-hydroxy-tamoxifen 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 - ∞). |
| 4-hydroxy-tamoxifen (Metabolite) 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. | — |
| 4-hydroxy-tamoxifen (Metabolite) 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. | Time for maximum observed plasma concentration. |
| 4-hydroxy-tamoxifen (Metabolite) 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. | Terminal half-life is the time measured for the plasma concentration to decrease by one half. |
| 4-hydroxy-tamoxifen (Metabolite) 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. | 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). |
| 4-hydroxy-tamoxifen (Metabolite) 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. | — |
| Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 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 | Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.250 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0. |
| Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 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 | 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. |
| Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 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 | Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.250 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0. |
| Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 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 | 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. |
| N-desmethyl-tamoxifen (Metabolite) 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. | 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). |
| 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. | Time for maximum observed plasma concentration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tamoxifen 40 mg, Tamoxifen 40 mg + DVS SR 100 mg Tamoxifen 40 mg as a single oral dose Period 1 / Day 1. DVS SR 100 mg as a single oral dose Period 2 / Day 1 through Day 6 (steady state) and Day 7 through Day 28. A single oral dose of Tamoxifen 40 mg coadministered with the DVS SR dose on Period 2 / Day 7. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1: TAMOX Alone | Adverse Event | 1 |
| Period 2: Coadministration TAMOX+DVS SR | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Tamoxifen 40 mg, Tamoxifen 40 mg + DVS SR 100 mg |
|---|---|
| Age, Customized 45 to 64 years | 27 participants |
| Age, Customized ≥65 years | 3 participants |
| Sex/Gender, Customized | 30 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 30 | 17 / 29 | 24 / 29 |
| serious Total, serious adverse events | 1 / 30 | 0 / 29 | 0 / 29 |
Outcome results
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
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 - ∞).
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | 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 ng*hr/mL | Standard Deviation 200.42 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | 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 | 505.6 ng*hr/mL | Standard Deviation 220.87 |
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
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).
Time frame: 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.
Population: Pharmacokinetic (PK) parameter analysis population: all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | 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 ng*hr/mL | Standard Deviation 1540.1 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 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 | 5888 ng*hr/mL | Standard Deviation 1905.5 |
Comparison: DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)90% CI: [96.7, 104.85]
Secondary
4-hydroxy-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen 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).
Time frame: 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.
Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.
Secondary
4-hydroxy-tamoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Time frame: 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.
Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.
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
4-hydroxy-tamoxifen 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 - ∞).
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | 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 ng*hr/mL | Standard Deviation 55.433 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | 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 | 133.9 ng*hr/mL | Standard Deviation 62.784 |
Comparison: DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)90% CI: [99.74, 111.81]
Secondary
4-hydroxy-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | 4-hydroxy-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 0.6716 ng/mL | Standard Deviation 0.1649 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | 4-hydroxy-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 0.7247 ng/mL | Standard Deviation 0.1799 |
Comparison: DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)90% CI: [103.51, 113.67]
Secondary
4-hydroxy-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | 4-hydroxy-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 165.2 hours | Standard Error 49.699 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | 4-hydroxy-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 177.0 hours | Standard Error 54.525 |
Secondary
4-hydroxy-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Time for maximum observed plasma concentration.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the median.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamoxifen 40 mg (Period 1) | 4-hydroxy-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 6.00 hours |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | 4-hydroxy-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 6.00 hours |
Secondary
Endoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen 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).
Time frame: 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.
Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.
Secondary
Endoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Time frame: 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.
Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.
Secondary
Endoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Endoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 1.077 ng/mL | Standard Deviation 0.4528 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Endoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 1.226 ng/mL | Standard Deviation 0.4956 |
Comparison: DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)90% CI: [84.71, 100]
Secondary
Endoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Endoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 207.5 hours | Standard Deviation 43.59 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Endoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 232.5 hours | Standard Deviation 56.719 |
Secondary
Endoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Time for maximum observed plasma concentration.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the median.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamoxifen 40 mg (Period 1) | Endoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 216 hours |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Endoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 120 hours |
Secondary
N-desmethyl-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen 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).
Time frame: 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.
Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.
Secondary
N-desmethyl-tamoxifen (Metabolite) Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Time frame: 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.
Population: PK parameter analysis population. Data was insufficient for analysis; not analyzable.
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
N-desmethyl-tamoxifen 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 - ∞).
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | 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 ng*hr/mL | Standard Deviation 1688 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | 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 | 9329 ng*hr/mL | Standard Deviation 2236.8 |
Secondary
N-desmethyl-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | N-desmethyl-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 18.30 ng/mL | Standard Deviation 3.7576 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | N-desmethyl-tamoxifen (Metabolite) Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 24.42 ng/mL | Standard Deviation 4.3709 |
Comparison: DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)90% CI: [107.44, 116.9]
Secondary
N-desmethyl-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | N-desmethyl-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 256.0 hours | Standard Error 24.042 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | N-desmethyl-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 265.6 hours | Standard Error 32.082 |
Secondary
N-desmethyl-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Time for maximum observed plasma concentration.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the median.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamoxifen 40 mg (Period 1) | N-desmethyl-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 35.9 hours |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | N-desmethyl-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 47.9 hours |
Secondary
Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
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.
Time frame: 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
Population: PK concentration analysis population. N=number of participants contributing to the median. Period 2 / Day 1 = Day 1 of Tamoxifen dosing (Period 2 / Day 7) within the DVS SR, Tamoxifen coadministration dosing period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | NA ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | NA ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | NA ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 0.2060 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 0.4335 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 0.5900 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 0.6145 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 0.6290 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 0.5910 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 0.4920 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 0.5395 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 0.4925 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 0.3795 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 0.2845 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 0.2180 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 0.1840 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 0.1590 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 0.1315 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 0.1125 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 0.5780 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | 0.0000 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 0.1180 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 0.4910 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 0.1600 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 0.2030 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 0.4010 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 0.3960 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 0.6420 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 0.2920 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 0.7060 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 0.1380 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 0.7100 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 0.2270 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 0.5860 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 0.5640 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 0.1870 ng/mL |
Secondary
Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
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.
Time frame: 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
Population: PK concentration analysis population. N=number of participants contributing to the median. Period 2 / Day 1 = Day 1 of Tamoxifen dosing (Period 2 / Day 7) within the DVS SR, Tamoxifen coadministration dosing period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 0.6215 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 0.1760 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 0.9065 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | NA ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 0.9740 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 0.2485 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 1.095 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 1.120 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 0.2895 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 1.120 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | NA ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 1.145 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 0.4470 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 1.035 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 0.8560 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 0.7060 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 0.4330 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 0.6210 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | NA ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 1.180 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | 0.2900 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | 0.3370 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | 0.3430 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 0.4100 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 0.5020 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 0.6350 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 0.5870 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 0.7310 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 0.7310 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 0.7130 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 0.9900 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 1.180 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 0.9760 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 1.240 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 1.140 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 1.080 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 1.160 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 0.9470 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 0.9150 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 0.7040 ng/mL |
Secondary
Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.250 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.
Time frame: 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
Population: PK concentration analysis population. N=number of participants contributing to the median. Period 2 / Day 1 = Day 1 of Tamoxifen dosing (Period 2 / Day 7) within the DVS SR, Tamoxifen coadministration dosing period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | NA ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | 0.0000 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | 0.8050 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 4.210 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 9.440 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 12.55 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 14.10 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 14.90 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 16.10 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 14.55 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 16.90 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 16.45 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 16.45 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 15.10 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 14.40 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 13.50 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 12.65 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 11.40 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 10.15 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 8.730 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 8.730 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 21.90 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | 3.600 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 13.10 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | 4.120 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 24.00 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | 5.650 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 15.40 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 9.770 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 19.80 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 14.80 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 10.40 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 18.70 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 19.80 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 19.30 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 14.40 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 20.40 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 16.80 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 19.00 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 10.50 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 18.40 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 15.60 ng/mL |
Secondary
Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
Summary statistics were to be calculated by setting concentration values below the lower limit of quantification (LLQ = 0.250 ng/mL) to zero. Summary statistics were not to be presented if number of observations above lower limit of quantification (NALQ) = 0.
Time frame: 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
Population: PK concentration analysis population: all participants randomized and treated who had at least 1 concentration in at least 1 treatment period. N=number of participants contributing to the median. Period 2 / Day 1 = Day 1 of Tamoxifen dosing (Period 2 / Day 7) within the DVS SR, Tamoxifen coadministration dosing period.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | NA ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | 1.875 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | 11.45 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 37.20 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 54.50 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 68.25 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 58.95 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 54.75 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 40.40 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 27.30 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 24.50 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 15.40 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 12.55 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 10.55 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 9.120 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 7.555 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 7.575 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 6.445 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 5.180 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 4.300 ng/mL |
| Tamoxifen 40 mg (Period 1) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 3.560 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 24 hours post dose | 25.50 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0 hour | 1.300 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 384 hours post dose | 5.600 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 0.5 hour post dose | 4.650 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 48 hours post dose | 16.20 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 1 hour post dose | 13.90 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 264 hours post dose | 7.270 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 2 hours post dose | 33.60 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 72 hours post dose | 12.60 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 3 hours post dose | 55.60 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 528 hours post dose | 4.160 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 4 hours post dose | 72.20 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 120 hours post dose | 11.60 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 6 hours post dose | 60.90 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 312 hours post dose | 6.920 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 8 hours post dose | 56.10 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 168 hours post dose | 9.930 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 12 hours post dose | 35.30 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 456 hours post dose | 4.330 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 16 hours post dose | 26.20 ng/mL |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR | 216 hours post dose | 8.150 ng/mL |
Secondary
Tamoxifen Apparent Clearance (CL/F) Following Tamoxifen 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).
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Tamoxifen Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR | 115.9 mL/min | Standard Deviation 34.544 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Tamoxifen Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR | 113.2 mL/min | Standard Deviation 44.545 |
Secondary
Tamoxifen Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Calculated as Dose / (AUCinf \* kel); where kel=terminal phase rate constant.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Tamoxifen Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR | 2474 liters | Standard Deviation 461.71 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Tamoxifen Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR | 2321 liters | Standard Deviation 419.76 |
Secondary
Tamoxifen Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Cmax measured as nanograms per milliliters (ng/mL).
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Tamoxifen Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 70.58 ng/mL | Standard Deviation 16.31 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Tamoxifen Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 70.33 ng/mL | Standard Deviation 14.484 |
Comparison: DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)90% CI: [94.02, 105.17]
Secondary
Tamoxifen Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tamoxifen 40 mg (Period 1) | Tamoxifen Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 250.5 hours | Standard Deviation 44.41 |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Tamoxifen Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR | 242.3 hours | Standard Deviation 51.851 |
Secondary
Tamoxifen Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Time for maximum observed plasma concentration.
Time frame: 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.
Population: PK parameter analysis population. N=number of participants contributing to the median.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamoxifen 40 mg (Period 1) | Tamoxifen Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 4.00 hours |
| Tamoxifen 40 mg + DVS SR 100 mg (Period 2) | Tamoxifen Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR | 4.00 hours |