A Pharmacokinetic Study to Evaluate the Bioequivalence of 2 Progesterone Vaginal Rings in Postmenopausal Women

Study Overview
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Brief Summary
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A study to assess the pharmacokinetics of 2 progesterone vaginal rings in postmenopausal women

Official Title
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An Open-Label, Single-Dose, Randomized, 2-Treatment, 2-Period Crossover Pharmacokinetic Study to Evaluate the Bioequivalence of 2 Progesterone Vaginal Rings 20% (w/w) in Postmenopausal Women

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: Progesterone vaginal ring,


Participation Criteria
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Eligibility Criteria
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Inclusion: Naturally postmenopausal woman with an intact uterus, 40 to 70 years of age, inclusive. The subject has serum estradiol and FSH levels that are consistent with the subject being postmenopausal. The subject has no clinically significant abnormality findings observed during pelvic, breast, and vaginal examination or based on mammogram and Pap smear evaluations. The subject will agree to be treated with 1 mg/day estradiol oral tablets for at least 28 days before insertion of the first vaginal ring and throughout the study. Exclusion: The subject has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, urologic, gynecologic, immunologic, dermatologic, neurologic, or psychiatric disease. The subject has a history of toxic shock syndrome. The subject has a history of jaundice associated with previous use of oral contraceptives. The subject has contraindications to the use of estrogen or progesterone that include, but are not limited to, the following: known sensitivity to estrogen or progesterone or related drugs known hypersensitivity to study medication ingredients, including FD&C Yellow No. 5 (tartrazine) present in estradiol tablets undiagnosed vaginal bleeding or high risk for endometrial cancer breast mass on examination known, suspected, or family history of estrogen- or progesterone-dependent neoplasia (now or in the past) The subject has low-grade squamous intraepithelial lesion (LSIL) or worse as observed in the Pap smear at screening. Any other abnormal finding on the Pap smear that the investigator considers clinically significant (such as atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion [HSIL; ASC-H], atypical glandular cells [AGC]); or any Pap result that would necessitate further evaluation by biopsy and/or colposcopy. The subject has any abnormal finding or condition deemed clinically significant by the investigator at screening that is a contraindication to the use of progestins, estrogen, or a vaginal ring. The subject has a positive pregnancy test at screening or at any time during the study. Current treatment with progesterone, other progestins, or estrogen (other than estradiol 1-mg tablets, progesterone 200-mg capsules, or medroxyprogesterone acetate 10-mg tablets required for this study purpose). Use of any of the following medications within the time frames noted below before the start of estrogen treatment: vaginal hormonal products (rings, creams, or gels) within 7 days transdermal estrogen alone or estrogen/progestin products within 28 days oral estrogen or progestin therapy within 56 days intrauterine progestin therapy within 56 days progestin implants or estrogen alone injectable drug therapy within 3 months estrogen pellet therapy or progestin injectable therapy within 6 months The subject has a vaginal ultrasonography at screening that confirms an active endometrial lining and/or an endometrial thickness of ≥4 mm.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>1 ring intravaginal for 7 days, produced from the new process | Drug: Progesterone vaginal ring,<br>* Participants will be randomized to receive treatments in 1 of 2 treatment sequences (AB or BA)<br>* Other names: 11 mg/day, produced from the LEGACY process;|
| Experimental: Treatment B<br>1 ring intravaginal for 7 days, produced from the legacy process | Drug: Progesterone vaginal ring,<br>* Participants will be randomized to receive treatments in 1 of 2 treatment sequences (AB or BA)<br>* Other names: 11 mg/day, produced from the LEGACY process;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| baseline-adjusted AUCt |  | 16 weeks | 
| baseline-adjusted AUC∞ |  | 16 weeks | 
| baseline-adjusted Cmax |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| baseline-adjusted tmax |  | 16 weeks | 
| baseline-unadjusted AUCt |  | 16 weeks | 
| baseline-adjusted λz |  | 16 weeks | 
| baseline-adjusted t½ |  | 16 weeks | 
| baseline-unadjusted AUC∞ |  | 16 weeks | 
| baseline-unadjusted Cmax |  | 16 weeks | 
| baseline-unadjusted tmax |  | 16 weeks | 
| baseline-unadjusted λz |  | 16 weeks | 
| baseline-unadjusted t½ |  | 16 weeks |