Study Evaluating Effects of Multiple-Dose Administration of Itraconazole on the Single Dose Pharmacokinetics of Conjugated Estrogens/Bazedoxifene in Non-Obese and Obese Postmenopausal Women

Study Overview
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Brief Summary
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This study will assess if itraconazole will affect the blood levels of Duavee when they are given together. This study will also assess if a subject's body size affects the blood levels of Duavee.

Official Title
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A Phase 1, Open Label, Two Period, Fixed Sequence, Parallel Group Study To Estimate The Effects Of Multiple Dose Administration Of Itraconazole On The Single Dose Pharmacokinetics Of Conjugated Estrogens/Bazedoxifene In Non Obese (Bmi <30 Kg/m2) And Obese (Bmi ≥30 Kg/m2) Postmenopausal Women

Conditions
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Healthy

Intervention / Treatment
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* Drug: CE/BZA
* Drug: Itraconazole
* Drug: CE/BZA
* Drug: CE/BZA
* Drug: Itraconazole
* Drug: CE/BZA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy postmenopausal women, aged 40-64. Intact Uterus Exclusion Criteria: The use of oral, vaginal, or transdermal estrogen, androgen or progestin-containing medications within 30 days before study drug administration.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Non-Obese<br>BMI <30 kg/m^2 | Drug: CE/BZA<br>* CE 0.45mg/BZA 20mg tablets, single dose<br>* Other names: Duavee;Drug: Itraconazole<br>* Two 100 mg capsules, once daily for 7 days<br>* Other names: Sporanox;Drug: CE/BZA<br>* CE 0.45mg/BZA 20mg tablets, single dose on Day 5<br>* Other names: Duavee;|
| Other: Obese<br>BMI >= 30 kg/m^2 | Drug: CE/BZA<br>* CE 0.45mg/BZA 20mg tablets, single dose<br>* Other names: Duavee;Drug: Itraconazole<br>* Two 100 mg capsules, once daily for 7 days<br>* Other names: Sporanox;Drug: CE/BZA<br>* CE 0.45mg/BZA 20mg tablets, single dose on Day 5<br>* Other names: Duavee;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] for BZA, total estrone adjusted for baseline and total equilin. | AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). | up to 96 hours | 
| Maximum Observed Plasma Concentration (Cmax) for BZA, total estrone adjusted for baseline and total equilin. |  | up to 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] for unconjugated estrone, unconjugated estrone adjusted for baseline, total estrone, and unconjugated equilin. | AUC (0 - inf)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). | up to 96 hours | 
| Maximum Observed Plasma Concentration (Cmax) for unconjugated estrone, unconjugated estrone adjusted for baseline, total estrone, and unconjugated equilin. |  | up to 96 hours | 
| Apparent Oral Clearance (CL/F) for all analytes. | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | up to 96 hours | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for all analytes. |  | up to 96 hours | 
| Apparent Volume of Distribution (Vz/F) for all analytes. | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | up to 96 hours | 
| Terminal Phase Elimination Half-Life (t1/2) for all analytes. | Terminal Phase Elimination Half-Life is the time measured for the plasma concentration to decrease by one half. | up to 96 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postmenopausal Women, Obese, Non-obese, Drug Interaction with Itraconazole, Pharmacokinetic