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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05367973




Registration number
NCT05367973
Ethics application status
Date submitted
2/05/2022
Date registered
10/05/2022
Date last updated
18/07/2023

Titles & IDs
Public title
Study of DARE-HRT1 Over 12 Weeks in Healthy PostMenopausal Women
Scientific title
A Phase 1/2,, Open-label, Parallel Group Study to Evaluate the Safety and Pharmacokinetics of DARE-HRT1 (80ug Estradiol/4 mg Progesterone and 160ug Estradiol/8 mg Progesterone Intravaginal Rings) Over 12 Weeks in Healthy Postmenopausal Women
Secondary ID [1] 0 0
DARE-HRT1-002
Universal Trial Number (UTN)
Trial acronym
DARE-HRT1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vulvovaginal Atrophy 0 0
Vasomotor Symptoms 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - IVR Dose 1
Treatment: Devices - IVR Dose 2

Experimental: IVR: Estradiol 80 ug/day + progesterone 4mg/day - 12-week IVR 80/4

Experimental: IVR Estradiol 160 ug/day + progesterone 8 mg/day - 12-week IVR 160/8


Treatment: Devices: IVR Dose 1
Estradiol 80 ug/day + progesterone 4 mg/day

Treatment: Devices: IVR Dose 2
Estradiol 160 ug/day + progesterone 8 mg/day
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment Emergent Adverse Events
Timepoint [1] 0 0
12 weeks
Primary outcome [2] 0 0
Determination of maximum plasma concentration (Cmax)
Timepoint [2] 0 0
12 weeks
Primary outcome [3] 0 0
Determination of time that maximum plasma concentration was observed (tmax)
Timepoint [3] 0 0
12 weeks
Primary outcome [4] 0 0
Determination of steady-state concentration (Css)
Timepoint [4] 0 0
12 weeks

Eligibility
Key inclusion criteria
1. 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).

The investigator will need to determine if a participant's BMI falling within the
obese-severely obese range could potentially interfere with the protocol-required
procedures, specifically the pelvic examinations described in Inclusion Criterion #2.
Any participant whose BMI is determined to fall into this category should be excluded
from trial participation.

2. Normal cervix, vagina, uterus, and adnexa based on speculum examination and bimanual
examination.

3. 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,

- If endometrial thickness is > 4.0 mm = 6.0 mm in a participant without
postmenopausal vaginal bleeding, an acceptable result from an evaluable screening
endometrial biopsy, evaluated by a pathologist, is required for inclusion into
the study. Tissue must be read as benign, inactive, or atrophic endometrium by at
least 1 pathologist,

4. Current on all Australian screening requirements for cervical cancer.

5. Able and willing to correctly and independently complete all study procedures.

6. 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.

7. 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.

8. Normal mammogram report within 24 months of screening.
Minimum age
No limit
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. 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.

2. Participants with any self-reported active sexually transmitted disease and/or
evidence of infection based on vaginal visual examination by the investigator.

3. 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).

4. Have a history of endometrial hyperplasia or cervical or uterine carcinoma.

5. Participants with indwelling catheters or requiring intermittent catheterization.

6. Participants with multiple or unsuccessful (e.g., still having symptoms) pelvic
reconstructive surgery, or who suffer from pelvic relaxation.

7. Participants who have had a hysterectomy.

8. 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.

9. 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.

10. Self-reported or observed vaginal irritation unrelated to VVA; vaginal, vulvar, or
cervical lesions, undiagnosed vaginal bleeding; or tenderness.

11. Participants with a finding of clinically significant uterine fibroids at screening.

12. Participants with a known hypersensitivity to progesterone, estradiol, Femring, or the
components of the IVR (e.g., ethylene vinyl acetate).

13. Participants with prior pelvic malignancies.

14. 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:

1. Human immunodeficiency virus (HIV) infection (confirmed by medical history/
serology testing),

2. Active chronic hepatitis B or hepatitis C infection including hepatitis B surface
antigen and hepatitis C antibody positive participants with or without abnormal
liver enzymes (confirmed by medical history/serology testing),

3. Concurrent neurodegenerative disease,

4. Cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction
or symptomatic congestive heart failure within the past 6 months, serious
uncontrolled cardiac arrhythmia, use of Class 1 antiarrhythmic medications, or
history of venous thromboembolism or stroke,

5. Dementia or significantly altered mental status that would prohibit the
understanding or rendering of informed consent and compliance with the
requirements of the protocol,

6. Participants with known thrombophilias may not participate in this study because
estrogen-based products are contraindicated for them,

7. Symptomatic bacterial vaginosis.

15. Fasting triglyceride of > 3.39 mmol/L and/or total cholesterol of > 7.77 mmol/L.

16. Aspartate aminotransferase or alanine aminotransferase > 1.5 times the upper limit of
normal.

17. Fasting glucose > 6.94 mmol/L.

18. Evidence of current alcohol or drug abuse in the past 60 days including a positive
result from the urine drugs of abuse or alcohol screen, or history of drug or alcohol
dependence in the last 2 years, as assessed by principal investigator. Alcohol abuse
is defined as greater than 14 standard units/week for females and drug abuse is
defined as known psychiatric or substance abuse disorder that would interfere with
participation with the requirements of this study, including current use of any
illicit drugs. Use of medical cannabis is not exclusionary.

19. Participation in any other investigational drug or device trial in which
administration of an investigational study drug/device occurred within 30 days or
placement of a non-drug eluting medical device within 15 days prior to screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/03/2023
Sample size
Target
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
Southern AustraliaWA
Recruitment hospital [1] 0 0
PARC Clinical Research - Adelaide
Recruitment hospital [2] 0 0
Keogh Institute for Medical Research - Nedlands
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Daré Bioscience, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05367973
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries