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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01189500
• Collaborator: (none)
• Enrollment: 30
• Locations: 2
• Arm: 1
• Duration (Months): 2
• Patients Per Site: 15
• Patients Per Site Per Month: 7.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics	Drug: Tamoxifen; Drug: Tamoxifen and Desvenlafaxine Succinate Sustained Release	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open-Label, 2-Period Sequential Drug Interaction Study To Evaluate The Effect Of A 100 Mg Dose Of Desvenlafaxine SR On The Pharmacokinetics Of Tamoxifen When Co-Administered In Healthy Post-Menopausal Female Subjects
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tamoxifen and Desvenlafaxine SR	Drug: Tamoxifen; Period 1-Tamoxifen 40mg on study day 1.; Drug: Tamoxifen and Desvenlafaxine Succinate Sustained Release; Period 2-Desvenlafaxine SR 100mg on days 1-28 with coadministration of Tamoxifen 40mg on day 7.

Outcome Measures

Primary Outcome Measures

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 [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).

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 [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 Outcome Measures

1. 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).

2. 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.

3. 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.

4. 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).

5. 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.

6. 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.]

7. 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.

8. 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.

9. 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).

10. 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.]

11. 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 - ∞).

12. 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.]

13. 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.

14. 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.

15. 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).

16. 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.]

17. 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 - ∞).

18. 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.]

19. 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.

20. 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.

21. 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).

22. 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.]

23. 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.

24. 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.

25. 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.

26. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Miami	Florida	United States	33126
2	Pfizer Investigational Site	Miami	Florida	United States	33134

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01189500
• Other Study ID Numbers: B2061027; 3151A1-1206
• First Posted: Aug 26, 2010
• Last Update Posted: Nov 6, 2011
• Last Verified: Nov 1, 2011

• Keywords provided by Pfizer: Pharmacokinetic; safety and tolerability; genetic testing; CYP 2D6
• Additional relevant MeSH terms: Tamoxifen; Desvenlafaxine Succinate

Study Results

Participant Flow

Arm/Group Title	Tamoxifen 40 mg, Tamoxifen 40 mg + DVS SR 100 mg
Arm/Group Description	Tamoxifen (TAMOX) 40 milligrams (mg) as a single oral dose Period 1 / Day 1. Desvenlafaxine sustained release (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.
Period Title: Period 1: TAMOX Alone
STARTED	30
COMPLETED	29
NOT COMPLETED	1
Period Title: Period 1: TAMOX Alone
STARTED	29
COMPLETED	28
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Tamoxifen 40 mg, Tamoxifen 40 mg + DVS SR 100 mg
Arm/Group Description	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.
Overall Participants	30
Age, Customized (participants) [Number]
45 to 64 years	27 90%
≥65 years	3 10%
Sex/Gender, Customized (participants) [Number]
Number [participants]	30 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	26	26
Geometric Mean (Standard Deviation) [ng*hr/mL]	5751 (1540.1)	5888 (1905.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen 40 mg (Period 1), Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	100.69
	Confidence Interval	(2-Sided) 90%; 96.70 to 104.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

2. Primary Outcome

Title	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
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	4	4
Geometric Mean (Standard Deviation) [ng*hr/mL]	677.7 (200.42)	505.6 (220.87)

3. Secondary Outcome

Title	Tamoxifen Maximum Observed Concentration (Cmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Geometric Mean (Standard Deviation) [ng/mL]	70.58 (16.310)	70.33 (14.484)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen 40 mg (Period 1), Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	99.44
	Confidence Interval	(2-Sided) 90%; 94.02 to 105.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

4. Secondary Outcome

Title	Tamoxifen Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the median.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Median (Full Range) [hours]	4.00	4.00

5. Secondary Outcome

Title	Tamoxifen Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	26	26
Mean (Standard Deviation) [hours]	250.5 (44.410)	242.3 (51.851)

6. Secondary Outcome

Title	Tamoxifen Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	26	26
Geometric Mean (Standard Deviation) [mL/min]	115.9 (34.544)	113.2 (44.545)

7. Secondary Outcome

Title	Tamoxifen Apparent Volume of Distribution (Vz/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	26	26
Geometric Mean (Standard Deviation) [liters]	2474 (461.71)	2321 (419.76)

8. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Geometric Mean (Standard Deviation) [ng/mL]	1.077 (0.4528)	1.226 (0.4956)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen 40 mg (Period 1), Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	92.04
	Confidence Interval	(2-Sided) 90%; 84.71 to 100.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

9. Secondary Outcome

Title	Endoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the median.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Median (Full Range) [hours]	216	120

10. Secondary Outcome

Title	Endoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	4	4
Mean (Standard Deviation) [hours]	207.5 (43.59)	232.5 (56.719)

11. Secondary Outcome

Title	Endoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	0	0

12. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	0	0

13. Secondary Outcome

Title	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
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	4	7
Geometric Mean (Standard Deviation) [ng*hr/mL]	8187 (1688.0)	9329 (2236.8)

14. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Geometric Mean (Standard Deviation) [ng/mL]	18.30 (3.7576)	24.42 (4.3709)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen 40 mg (Period 1), Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	112.07
	Confidence Interval	(2-Sided) 90%; 107.44 to 116.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

15. Secondary Outcome

Title	N-desmethyl-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the median.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Median (Full Range) [hours]	35.9	47.9

16. Secondary Outcome

Title	N-desmethyl-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	4	7
Mean (Standard Error) [hours]	256.0 (24.042)	265.6 (32.082)

17. Secondary Outcome

Title	N-desmethyl-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	0	0

18. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	0	0

19. Secondary Outcome

Title	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
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	25	26
Geometric Mean (Standard Deviation) [ng*hr/mL]	117.5 (55.433)	133.9 (62.784)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen 40 mg (Period 1), Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	105.60
	Confidence Interval	(2-Sided) 90%; 99.74 to 111.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

20. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Geometric Mean (Standard Deviation) [ng/mL]	0.6716 (0.1649)	0.7247 (0.1799)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tamoxifen 40 mg (Period 1), Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Comments	DVS SR 100 mg + Tamoxifen 40 mg (test) versus Tamoxifen 40 mg (reference)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	ratio of adjusted means
	Estimated Value	108.47
	Confidence Interval	(2-Sided) 90%; 103.51 to 113.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Values have been back-transformed from the log scale.

21. Secondary Outcome

Title	4-hydroxy-tamoxifen (Metabolite) Time for Cmax (Tmax) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the median.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
Median (Full Range) [hours]	6.00	6.00

22. Secondary Outcome

Title	4-hydroxy-tamoxifen (Metabolite) Terminal Half-life (t 1/2) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. N=number of participants contributing to the mean.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	25	26
Mean (Standard Error) [hours]	165.2 (49.699)	177.0 (54.525)

23. Secondary Outcome

Title	4-hydroxy-tamoxifen (Metabolite) Apparent Clearance (CL/F) Following Tamoxifen Alone and When Coadministered With DVS SR
Description	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	0	0

24. Secondary Outcome

Title	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.

Outcome Measure Data

Analysis Population Description

PK parameter analysis population. Data was insufficient for analysis; not analyzable.

Arm/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	0	0

25. Secondary Outcome

Title	Plasma Tamoxifen Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
0 hour	NA	1.300
0.5 hour post dose	1.875	4.650
1 hour post dose	11.45	13.90
2 hours post dose	37.20	33.60
3 hours post dose	54.50	55.60
4 hours post dose	68.25	72.20
6 hours post dose	58.95	60.90
8 hours post dose	54.75	56.10
12 hours post dose	40.40	35.30
16 hours post dose	27.30	26.20
24 hours post dose	24.50	25.50
48 hours post dose	15.40	16.20
72 hours post dose	12.55	12.60
120 hours post dose	10.55	11.60
168 hours post dose	9.120	9.930
216 hours post dose	7.555	8.150
264 hours post dose	7.575	7.270
312 hours post dose	6.445	6.920
384 hours post dose	5.180	5.600
456 hours post dose	4.300	4.330
528 hours post dose	3.560	4.160

26. Secondary Outcome

Title	Plasma Endoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
0 hour	NA	0.2900
0.5 hour post dose	NA	0.3370
1 hour post dose	NA	0.3430
2 hours post dose	0.0000	0.4100
3 hours post dose	0.0000	0.5020
4 hours post dose	0.1760	0.6350
6 hours post dose	0.2485	0.5870
8 hours post dose	0.2895	0.7310
12 hours post dose	0.4470	0.7310
16 hours post dose	0.4330	0.7130
24 hours post dose	0.6215	0.9900
48 hours post dose	0.9065	1.180
72 hours post dose	0.9740	1.180
120 hours post dose	1.095	1.240
168 hours post dose	1.120	1.140
216 hours post dose	1.120	1.080
264 hours post dose	1.145	1.160
312 hours post dose	1.035	0.9760
384 hours post dose	0.8560	0.9470
456 hours post dose	0.7060	0.9150
528 hours post dose	0.6210	0.7040

27. Secondary Outcome

Title	Plasma N-desmethyl-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
0 hour	NA	3.600
0.5 hour post dose	0.0000	4.120
1 hour post dose	0.8050	5.650
2 hours post dose	4.210	9.770
3 hours post dose	9.440	14.80
4 hours post dose	12.55	18.70
6 hours post dose	14.10	19.30
8 hours post dose	14.90	20.40
12 hours post dose	16.10	19.00
16 hours post dose	14.55	18.40
24 hours post dose	16.90	21.90
48 hours post dose	16.45	24.00
72 hours post dose	16.45	19.80
120 hours post dose	15.10	19.80
168 hours post dose	14.40	16.80
216 hours post dose	13.50	15.60
264 hours post dose	12.65	15.40
312 hours post dose	11.40	14.40
384 hours post dose	10.15	13.10
456 hours post dose	8.730	10.50
528 hours post dose	8.730	10.40

28. Secondary Outcome

Title	Plasma 4-hydroxy-tamoxifen (Metabolite) Concentration Versus Time Summary: Tamoxifen Alone and When Coadministered With DVS SR
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Tamoxifen 40 mg (Period 1)	Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose Period 1 / Day 1.	DVS SR 100 mg as a single oral daily 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.
Measure Participants	30	29
0 hour	NA	0.0000
0.5 hour post dose	NA	0.0000
1 hour post dose	NA	0.0000
2 hours post dose	0.2060	0.2030
3 hours post dose	0.4335	0.3960
4 hours post dose	0.5900	0.6420
6 hours post dose	0.6145	0.7060
8 hours post dose	0.6290	0.7100
12 hours post dose	0.5910	0.5860
16 hours post dose	0.4920	0.5640
24 hours post dose	0.5395	0.5780
48 hours post dose	0.4925	0.4910
72 hours post dose	0.3795	0.4010
120 hours post dose	0.2845	0.2920
168 hours post dose	0.2180	0.2270
216 hours post dose	0.1840	0.1870
264 hours post dose	0.1590	0.1600
312 hours post dose	0.1315	0.1380
384 hours post dose	0.1125	0.1180
456 hours post dose	0.0000	0.0000
528 hours post dose	0.0000	0.0000

Adverse Events

Time Frame	Baseline up to Day 36 (follow-up telephone visit)
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. Participants are counted for each treatment sequence.
Arm/Group Title	Tamoxifen 40 mg (Period 1)		DVS SR 100 mg (Period 2)		Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
Arm/Group Description	Tamoxifen 40 mg as a single oral dose on Period 1 / Day 1.		DVS SR 100 mg as a single oral daily dose Period 2 / Day 1 through Day 6 (steady state) and Day 7 through Day 28.		Tamoxifen 40 mg as a single oral dose coadministered with DVS SR 100 mg as a single oral dose on Period 2 / Day 7.
All Cause Mortality
	Tamoxifen 40 mg (Period 1)		DVS SR 100 mg (Period 2)		Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tamoxifen 40 mg (Period 1)		DVS SR 100 mg (Period 2)		Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Hepatobiliary disorders
Cholecystitis	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Cholelithiasis	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Tamoxifen 40 mg (Period 1)		DVS SR 100 mg (Period 2)		Tamoxifen 40 mg + DVS SR 100 mg (Period 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/30 (36.7%)		17/29 (58.6%)		24/29 (82.8%)
Cardiac disorders
Palpitations	0/30 (0%)		0/29 (0%)		7/29 (24.1%)
Eye disorders
Eye swelling	0/30 (0%)		1/29 (3.4%)		0/29 (0%)
Vision blurred	0/30 (0%)		1/29 (3.4%)		1/29 (3.4%)
Gastrointestinal disorders
Abdominal pain	0/30 (0%)		0/29 (0%)		3/29 (10.3%)
Constipation	2/30 (6.7%)		6/29 (20.7%)		3/29 (10.3%)
Diarrhoea	1/30 (3.3%)		1/29 (3.4%)		0/29 (0%)
Dry mouth	0/30 (0%)		1/29 (3.4%)		3/29 (10.3%)
Dyspepsia	0/30 (0%)		2/29 (6.9%)		3/29 (10.3%)
Gastrooesophageal reflux disease	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Nausea	0/30 (0%)		4/29 (13.8%)		2/29 (6.9%)
Toothache	0/30 (0%)		0/29 (0%)		3/29 (10.3%)
Vomiting	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
General disorders
Chills	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Fatigue	1/30 (3.3%)		0/29 (0%)		2/29 (6.9%)
Infections and infestations
Gastroenteritis viral	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Tooth infection	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Upper respiratory tract infection	0/30 (0%)		0/29 (0%)		4/29 (13.8%)
Vaginitis bacterial	0/30 (0%)		1/29 (3.4%)		1/29 (3.4%)
Investigations
Blood pressure increased	0/30 (0%)		1/29 (3.4%)		0/29 (0%)
Weight decreased	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/30 (0%)		0/29 (0%)		3/29 (10.3%)
Back pain	1/30 (3.3%)		2/29 (6.9%)		3/29 (10.3%)
Muscle spasms	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Muscle twitching	0/30 (0%)		1/29 (3.4%)		1/29 (3.4%)
Musculoskeletal pain	2/30 (6.7%)		0/29 (0%)		0/29 (0%)
Pain in extremity	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Nervous system disorders
Balance disorder	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Dizziness	0/30 (0%)		1/29 (3.4%)		3/29 (10.3%)
Headache	1/30 (3.3%)		1/29 (3.4%)		9/29 (31%)
Hypoaesthesia	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Paraesthesia	0/30 (0%)		1/29 (3.4%)		0/29 (0%)
Somnolence	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Tremor	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Psychiatric disorders
Anxiety	0/30 (0%)		0/29 (0%)		3/29 (10.3%)
Insomnia	0/30 (0%)		2/29 (6.9%)		8/29 (27.6%)
Nightmare	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Restlessness	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Renal and urinary disorders
Dysuria	0/30 (0%)		0/29 (0%)		1/29 (3.4%)
Reproductive system and breast disorders
Pelvic pain	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/30 (3.3%)		0/29 (0%)		0/29 (0%)
Rhinorrhoea	0/30 (0%)		1/29 (3.4%)		2/29 (6.9%)
Skin and subcutaneous tissue disorders
Erythema	0/30 (0%)		1/29 (3.4%)		0/29 (0%)
Hyperhidrosis	1/30 (3.3%)		0/29 (0%)		0/29 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.