Study of DARE-HRT1 Over 12 Weeks in Healthy PostMenopausal Women

NCT05367973 | Completed Phase 1 Results

• 1 other identifier: DARE-HRT1-002
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

Randomized, Open-label 2-arm, parallel group study in approximately 20 healthy postmenopausal women to assess the safety of DARE-HRT1 Intravaginal Rings in two different dose strengths and the PK of progesterone and estradiol from the Intravaginal Rings.

Conditions

Vulvovaginal Atrophy; Vasomotor Symptoms

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Treatment Emergent Adverse Events

  To assess the safety and tolerability of DARE-HRT1 Intravaginal rings

  12 weeks

• Determination of Maximum Plasma Concentration of Progesterone (Cmax) Per Cycle

  To describe the Pharmacokinetic parameters of dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

  12 weeks (3- 28 day cycles)

• Determination of Time That Maximum Progesterone Plasma Concentration Was Observed (Tmax)

  To describe the Pharmacokinetic parameters of dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

  12 weeks (3- 28 day cycles)

• Determination of Progesterone Steady-state Concentration (Css) Per Cycle

  To describe the Pharmacokinetic parameters of dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

  12 weeks (3- 28day cycles)

• Determination of Time That Maximum Estradiol Plasma Concentration Was Observed (Tmax)

  To describe the Pharmacokinetic parameters of dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

  12 weeks (3- 28 day cycles)

• Determination of Maximum Plasma Concentration of Estradiol (Cmax) Per Cycle

  To describe the Pharmacokinetic parameters of dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

  12 weeks (3- 28 day cycles)

• Determination of Estradiol Steady-state Concentration (Css) Per Cycle

  To describe the Pharmacokinetic parameters of dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

  12 weeks (3- 28day cycles)

Other Outcomes (4)

• Evaluation of Responses to The Menopause-Specific Quality-of-Life Questionnaire (MENQOL)

  12 weeks

• Evaluation of Vaginal Cytology

  12 weeks

• Evaluation of Vaginal pH

  12 weeks

Study Arms (2)

IVR: Estradiol 80 ug/day + progesterone 4mg/day

EXPERIMENTAL

12-week IVR 80/4

Device: IVR Dose 1

IVR Estradiol 160 ug/day + progesterone 8 mg/day

EXPERIMENTAL

12-week IVR 160/8

Device: IVR Dose 2

Interventions

IVR Dose 1 DEVICE

Estradiol 80 ug/day + progesterone 4 mg/day

IVR: Estradiol 80 ug/day + progesterone 4mg/day

IVR Dose 2 DEVICE

Estradiol 160 ug/day + progesterone 8 mg/day

IVR Estradiol 160 ug/day + progesterone 8 mg/day

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women with a body mass index (BMI) ≥ 18 and ≤ 38 kg/m2. BMI = weight (kg)/(height \[m\])2
• Postmenopausal is defined as 12-months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy (although participants who have had a hysterectomy are not eligible for this study).
• Normal cervix, vagina, uterus, and adnexa based on speculum examination and bimanual examination.
• Normal transvaginal ultrasound, and endometrial biopsy results as follows:
• If endometrial thickness is ≤ 4.0 mm in a participant without postmenopausal vaginal bleeding, an endometrial biopsy is not indicated for the purposes of screening,
• Current on all Australian screening requirements for cervical cancer.
• Able and willing to correctly and independently complete all study procedures.
• Able and willing to stop any ongoing HRT in accordance with the appropriate washout periods (see Section 4.1 for washout requirements). Participants who are using HRT that requires more than 8 weeks to wash out (e.g., progestogen implants or progestogen injectable drug therapy, estrogen alone injectable drug therapy or estrogen pellet therapy) will not be eligible.
• Able to read, understand, and provide written informed consent after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures.
• Normal mammogram report within 24 months of screening.

You may not qualify if:

• Prior abnormal cervical screening test or Papanicolaou result within 2 years of screening. Participant can have atypical squamous cells of undetermined significance, if human papillomavirus negative.
• Participants with any self-reported active sexually transmitted disease and/or evidence of infection based on vaginal visual examination by the investigator.
• Participants with a urinary tract infection during screening as assessed by urine dipstick test with abnormal test findings (any positive result for leukocytes AND any positive result for nitrites).
• Have a history of endometrial hyperplasia or cervical or uterine carcinoma.
• Participants with indwelling catheters or requiring intermittent catheterization.
• Participants with multiple or unsuccessful (e.g., still having symptoms) pelvic reconstructive surgery, or who suffer from pelvic relaxation.
• Participants who have had a hysterectomy.
• Participants taking any estrogen and/or progesterone products who are not willing to stop this treatment during their participation in this trial (see Section 4.1 for washout requirements). Participants who are using HRT that requires more than 8 weeks to wash out (e.g., progestogen implants or progestogen injectable drug therapy, estrogen alone injectable drug therapy or estrogen pellet therapy) will not be eligible.
• Participants with concomitant use of personal lubricants (water-based lubricants are allowed) or any intravaginal product or medication, either by prescription or over-the-counter (OTC) (e.g., Femring \[estradiol acetate vaginal ring\], ESTRING® \[estradiol vaginal ring\]) with the exception of those who agree not to use these products during the IVR use period.
• Self-reported or observed vaginal irritation unrelated to VVA; vaginal, vulvar, or cervical lesions, undiagnosed vaginal bleeding; or tenderness.
• Participants with a finding of clinically significant uterine fibroids at screening.
• Participants with a known hypersensitivity to progesterone, estradiol, Femring, or the components of the IVR (e.g., ethylene vinyl acetate).
• Participants with prior pelvic malignancies.
• Participants with a history of any severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or study treatment administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the participant inappropriate for entry into the trial. This includes but is not limited to the following:
• Human immunodeficiency virus (HIV) infection (confirmed by medical history/ serology testing),

Sponsors & Collaborators

• Daré Bioscience, Inc.: lead

Study Sites (2)

PARC Clinical Research

Adelaide, Southern Australia, 5000, Australia

Location

Keogh Institute for Medical Research

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (2)

• Thurman A, Hull ML, Stuckey B, Hatheway J, Zack N, Mauck C, Friend D. A phase 1/2, open-label, parallel group study to evaluate the preliminary efficacy and usability DARE-HRT1 (80 mug estradiol/4 mg progesterone and 160 mug estradiol/8 mg progesterone intravaginal RinGSM) over 12 weeks in healthy postmenopausal women. Menopause. 2023 Sep 1;30(9):940-946. doi: 10.1097/GME.0000000000002230. Epub 2023 Aug 7.

  PMID: 37625088 DERIVED

• Thurman A, Hull ML, Stuckey B, Hatheway J, Zack N, Mauck C, Friend D. A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 mug estradiol/4 mg progesterone and 160 mug estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women. Menopause. 2023 Aug 1;30(8):817-823. doi: 10.1097/GME.0000000000002210. Epub 2023 Jun 20.

  PMID: 37339390 DERIVED

Results Point of Contact

• Title: Jessica Hatheway, VP Clinical Operations
• Organization: Dare Bioscience, Inc.

jhatheway@darebioscience.com

858-926-7655

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 10, 2022
• Study Start: April 11, 2022
• Primary Completion: January 9, 2023
• Study Completion: March 23, 2023
• Last Updated: October 31, 2024
• Results First Posted: October 31, 2024

Record last verified: 2024-10

Locations

AU (2)