A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women

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dc.contributor.authorThurman, A.
dc.contributor.authorHull, M.L.
dc.contributor.authorStuckey, B.
dc.contributor.authorHatheway, J.
dc.contributor.authorZack, N.
dc.contributor.authorMauck, C.
dc.contributor.authorFriend, D.
dc.date.issued2023
dc.descriptionPublished August 2023
dc.description.abstractObjectives: Primary objectives were to evaluate the safety and systemic pharmacokinetics (PK) of DARE-HRT1, an intravaginal ring (IVR), which releases 17β2-Estradiol (E2) with progesterone (P4) for 28 days in healthy postmenopausal women. Methods: This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women with an intact uterus. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d). They used the IVR for three 28-day cycles, inserting a new IVR monthly. Safety was measured by treatment emergent adverse events and changes in systemic laboratories and the endometrial bilayer width. Baseline adjusted plasma PK of E2, P4, and estrone (E1) was described. Results: Both DARE-HRT1 IVR were safe. All treatment emergent adverse events were mild or moderate and were distributed similarly among IVR1 versus IVR2 users. Month 3 median maximum plasma (Cmax) P4 concentrations were 2.81 and 3.51 ng/mL and Cmax E2 was 42.95 and 77.27 pg/mL for IVR1 and IVR2 groups, respectively. Month 3 median steady state (Css) plasma P4 concentrations were 1.19 and 1.89 ng/mL, and Css E2 was 20.73 and 38.16 pg/mL for IVR1 and IVR2 users, respectively. Conclusions: Both DARE-HRT1 IVRs were safe and released E2 in systemic concentrations, which were in the low, normal premenopausal range. Systemic P4 concentrations predict endometrial protection. Data from this study support further development of DARE-HRT1 for the treatment of menopausal symptoms.
dc.description.statementofresponsibilityAndrea Thurman, Louise Hull, Bronwyn Stuckey, Jessica Hatheway, Nadene Zack, Christine Mauck and David Friend
dc.identifier.citationMenopause: The Journal of the North American Menopause Society, 2023; 30(8):817-823
dc.identifier.doi10.1097/gme.0000000000002210
dc.identifier.issn1072-3714
dc.identifier.issn1530-0374
dc.identifier.orcidHull, M.L. [0000-0003-1813-3971] [0000-0003-4660-4005]
dc.identifier.urihttps://hdl.handle.net/2440/138889
dc.language.isoen
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.rights© 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The North American Menopause Society. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
dc.source.urihttps://doi.org/10.1097/gme.0000000000002210
dc.subjectIntravaginal ring; Menopausal symptoms; Pharmacokinetics; Safety; Vasomotor symptoms
dc.titleA phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women
dc.typeJournal article
pubs.publication-statusPublished

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