Data on safety and pharmacokinetics of DARE-HRT1 published

Data on safety and pharmacokinetics of DARE-HRT1 published | Image Credit: © wladimir1804 - © wladimir1804 - stock.adobe.com.

Data from a phase 1/2 clinical trial on the safety and pharmacokinetics (PK) of DARE-HRT1 has been published by Daré Bioscience in Menopause, the journal of the North American Menopause Society.¹

DARE-HRT1 is an intravaginal ring (IVR)providing hormone therapy for 28 days by releasing bio-identical 17β2-estradiol (E2) and bio-identical progesterone (P4). The product was developed by William Crowley, MD from Massachusetts General Hospital and Harvard Medical School and Robert Langer, ScD, from the Massachusetts Institute of Technology.

The randomized, open-label, 2-arm parallel group study included 21 patients taking either IVR1 (E2 80 μg/d with P4 4 mg/d) or IVR2 (E2 160 μg/d with P4 8 mg/d)over a 12-week period.² IVRs remained inserted throughout 28-day periods, and were replaced every month.

Eligibility criteria was listedas being healthy and postmenopausal, not using tobacco products or exogenous hormones, and having a body index from 18 kg/m² to 38 kg/m², an endometrial thickness of 4 mm or less, a normal mammogram within 2 years of screening visit, and normal cervical cytology cancer screening.

Patients with postmenopausal bleeding, sexually transmitted infection, endometrial hyperplasia history, or a disease preventing compliance were excluded. Menopause was, “defined by 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with a plasma follicle stimulating hormone concentration of 40 mIU/mL or higher.”

Systemic laboratory and endometrial bilayer width changes were reported, along with treatment emergent adverse events (TAEs).Adverse events included vaginal discharge, pelvic pain, and vaginal or vulvar irritation. Unintended adverse responses to the product, known as adverse drug reactions, were also reported.

Clinical laboratory assessments, vital signs, measurements of endometrial thickness width, physical examinations, and 12-lead electrocardiograms were also performed to evaluate safety. When evaluating PK, estrogen (E1), E2, and P4 were measured. PK measurements occurred at 0.5, 1-, 2-, 4-, and 8-hours following insertion on day 1.

For the final cycle, PK measurements occurred, 0.5, 1, 2, 4, 8, and 24 hours following IVR removal. Agilex Biolabs performed evaluations of E1, E2, and P4 measurements. Among patients in the IVR1 group, there were 35 TAEs reported, compared to 62 among participants in the IVR2 group. In both groups, no TAEs were severe.

In the IVR1 group, the mean endometrial thickness was 2.40 mm at baseline and 3.03 mm at the end of treatment, compared to 2.11 mm and 2.50 mm respectively in the IVR2 group. These results indicated overall positive safety and PK.

There are currently no products providingcombination bio-identical estradiol and bio-identical progesterone through vaginal therapy approved by the FDA, making DARE-HRT1 potentially the first.¹ 

In the future, there will be a phase 3 trial evaluating the efficacy of DARE-HRT1 against severe vasomotor symptoms of menopause (VMS). Daré Bioscience plans to submitDARE-HRT1 to the FDA for approval in treating severe VMS in menopausal women with intact uteri.

Reference

1. Daré Bioscience announces publication in Menopause: The Journal of The North American Menopause Society of data from phase 1/2 open-label safety and pharmacokinetics study of DARE-HRT1 in healthy postmenopausal women.Daré Bioscience. June 21, 2023. Accessed June 22, 2023. https://ir.darebioscience.com/news-releases/news-release-details/dare-bioscience-announces-publication-menopause-journal-north-0

2. Thurman H, Hull LM, Stuckey B, et al.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. Menopause. 2023. doi:10.1097/GME.0000000000002210