Vulvar AtrophyPhase 1/2DARE-VVA1NCT05378269

Study of Intravaginal Tamoxifen in PostMenopausal Women With VVA

A Phase 1/2 study testing Tamoxifen in people with Vulvar Atrophy, run by Daré Bioscience, Inc. at 2 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of the study is to study the safety, PK and PD of Intravaginal Tamoxifen on postmenopausal women with vulvar vaginal atrophy. Read more about this study

Who is it for?: Ages 40 to 75 years, women onlyHealthy volunteers can take part
Conditions the study is for: Vulvar Atrophy
What is being tested?: Tamoxifen
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 17 participants
Where: 2 sitesAustralia
Study dates: 22 Nov 2021to 1 Mar 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 to 75 years
Women only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

1. Women aged 40-75 (inclusive).
2. Postmenopausal women with a body mass index between 18 and 34 kg/m2, inclusive.
3. Postmenopausal, defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels > 40 mIU/mL or 6 weeks post-surgical bilateral oophorectomy.
4. Have moderate to severe VVA as determined by self-assessment of the following symptoms (as none, mild, moderate, or severe), with at least 1 symptom reported as moderate or severe: vaginal dryness; vaginal and/or vulvar irritation/itching; dysuria; vaginal pain with sexual activity (dyspareunia); vaginal bleeding associated with sexual activity (presence versus absence).
5. Women who currently have vaginal intercourse or other sexual activity (masturbation, etc.) at least once a month (with or without a partner), or who had intercourse or other sexual activity at least once a month in the past, but later decreased sexual activity due to excessive pain or vaginal dryness. Participants must be willing to engage in vaginal intercourse or other sexual activity (masturbation, etc.) at least 1 time between Days 49-56 of the clinical study.
6. Participants, upon pelvic examination with speculum examination, must have a normal-appearing vulva other than atrophic changes, normal-appearing cervix other than atrophic changes (i.e., cervical stenosis and/or flushness with the vaginal wall) and normal-appearing vagina (without erosions, ulcerations, scarring, or evidence of dermatoses) other than atrophic changes (loss of ruggae, mucosal pallor, mucosal dryness, mucosal petechiae).

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7. Have an intact uterus and no prior history of endometrial ablation.
8. Vaginal cellular cytology with ≤ 5% superficial cells.
9. Vaginal pH > 5 at Screening Visit.
10. Endometrial thickness ≤ 4 mm on transvaginal ultrasound.
11. Current on all recommended screening and management requirements for cervical cancer.
12. Normal mammogram report within 2 years of screening.
13. Normal manual breast examination by investigator at baseline.
14. Baseline hematology, clinical chemistry, urinalysis, prothrombin time/partial thromboplastin time (PT/PTT) and viral serologies for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B surface antigen (HBsAg) all within normal limits OR accepted by the investigator and medical monitor as not clinically significant.
15. Normal 12-lead electrocardiogram (ECG).
16. Able to read, understand, and provide written informed consent and applicable data protection authorization after the nature of the study has been fully explained, and must be willing to comply with all study requirements.
17. Willing and able to correctly and independently complete all study procedures.

Who cannot join

A history of or physical examination finding for any significant cardiovascular, renal, pulmonary, neurological and hepatic diseases preventing compliance with this study.
A medical history of or use of anticoagulant drugs to treat or prevent coagulopathies, thrombophilia or thromboembolic disease (deep vein thrombosis, pulmonary or systemic embolism, stroke, or transient ischemic attack).
Uncontrolled hypertension (either systolic > 180 mmHg or diastolic > 105 mmHg), treatment with Class 1 antiarrhythmics or digitalis, history of congestive heart failure (New York Heart Association [NYHA] > Class I), or myocardial infarction within 12 months.
Abnormal cervical screening test within 2 years of screening. Participant can have atypical squamous cells of undetermined significance if human papilloma virus-negative.
History of or current endometrial pathology: hyperplasia, carcinoma and/or polyp (prior history of a benign endometrial polyp with no current evidence of polyp is acceptable).
A medical history of breast cancer within 5 years of screening. Participants with a history of breast cancer more than 5 years prior to screening are considered eligible if their disease was node-negative, nonmetastatic, and if all treatment with aromatase inhibitors (AIs) or SERMs was completed at least 6 months prior to screening.

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A medical history of malignant melanoma.
Any cancer (except nonmelanomatous skin cancer) diagnosed less than 5 years prior to the Screening Visit.
A medical history of undiagnosed vaginal bleeding.
A known or suspected estrogen-dependent neoplasia.
Previous radiation treatment to the pelvis.
Women who have previously reported an unsatisfactory outcome from a vaginal hormone therapy for VVA.
Known hypersensitivity to any ingredients in DARE-VVA1.
Use of vaginal hormonal products (rings, creams, gels, tablets, capsules) within 4 weeks prior to Day 1.
Use of transdermal estrogen or transdermal estrogen/progestin products within 4 weeks prior to Day 1.
Use of oral estrogen and/or progestin therapy within 8 weeks prior to Day 1.
Use of intrauterine progestin therapy within 8 weeks prior to Day 1.
Use of progestin implants or estrogen-alone injectable drug therapy within 12 weeks prior to Day 1.
Administration of estrogen pellet therapy or progestin injectable drug therapy within 6 months prior to Day 1.
Use of thyroid hormone replacement therapy unless the participant is on a stable dose for > 6 months, and participant is euthyroid based on a normal, sensitive immunoassay for thyroid-stimulating hormone (TSH).
Use of SERMs or AIs within 6 months prior to screening.
Use of anabolic or other steroids (including hormonal creams such as testosterone) within 4 weeks prior to Day 1.
Use of corticosteroids, > 5 mg/day prednisone or equivalent, for more than 4 weeks within 4 weeks prior to Day 1.
Participants with any self-reported active sexually transmitted disease and/or evidence of infection (including bacterial vaginosis) on vaginal 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).
Presence of clinically significant uterine fibroids.
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 the 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.
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 the Screening Visit (Visit 1).
In the opinion of the investigator, participant has any disorder or finding that might interfere with the conduct of the study.

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

PARC Clinical Research
Adelaide, Southern Australia, 5000
Keogh Institute for Medical Research
Nedlands, Western Australia, 6009

Other trials in Australia

About this study

Official title: Phase 1/2 Study of Intravaginal Tamoxifen (DARE-VVA1): Randomized, Double-blind, Placebo-controlled Study of Safety, Pharmacokinetics and Pharmacodynamics in Postmenopausal Participants With Moderate to Sever Vulvar and Vaginal Atrophy

The purpose of the study is to study the safety, PK and PD of Intravaginal Tamoxifen on postmenopausal women with vulvar vaginal atrophy.

Conditions: Vulvar Atrophy
Being tested: Tamoxifen, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TamoxifenDrug
Tamoxifen vaginal insert
PlaceboOther
Placebo vaginal insert

Study groups in NCT05378269
Study group	Role	What they receive
Placebo	Placebo comparator	Vaginal insert Receives: Other: Placebo
DARE-VVA1 1mg	Experimental	vaginal insert Receives: Drug: Tamoxifen
DARE-VVA1 5mg	Experimental	vaginal insert Receives: Drug: Tamoxifen
DARE-VVA1 10mg	Experimental	vaginal insert Receives: Drug: Tamoxifen
DARE-VVA1 20mg	Experimental	vaginal insert Receives: Drug: Tamoxifen

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Subjects With Treatment Emergent Adverse Events
to evaluate the safety and tolerability of DARE-VVA1 by intravaginal administration
Measured: 56 days
Concentration of Tamoxifen in Serial Plasma Collections (Cmax)
to determine the plasma concentrations of tamoxifen after intravaginal administration
Measured: 56 days

Secondary outcomes (3)

Evaluation of Vaginal Cytology
to analyze the change from baseline to end of study of percentage of parabasal cells
Measured: 56 days
Evaluation of Vaginal pH
to analyze preliminary efficacy and pharmacodynamics of DARE-VVA1 by looking at change in baseline of vaginal pH from Day 1 to Day 56
Measured: 56 days
Evaluation of Vaginal Cytology
to analyze the change from baseline to end of study of percentage of superficial cells
Measured: 56 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Nov 20211 Mar 2023

First posted18 May 2022
Study start22 Nov 2021
Primary completion20 Dec 2022
Study completion1 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Vulvar AtrophyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05378269
Sponsor's protocol ID: DARE-VVA-001
Acronym: DARE-VVA1
Status last verified: Jul 2024
First submitted: 2 May 2022
Last updated: 21 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: A decision has not yet been made on when or what IPD to share when available.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
Retrospective Cohort Study of Symptoms and Quality of Life in Women With Genitourinary Syndrome of Menopause.
Vulvar Atrophy, Vulvovaginal Signs and Symptoms
Active, not recruiting
Laser Vaginal Treatment for GSM
Menopausal Urethral Atrophy, Vulvar Atrophy
Recruiting
Changes in the Impact of Genitourinary Syndrome of Menopause With a Novel Nonhormonal Vulvovaginal Gel Assessed by PROMs.
Vulvar Atrophy, Vulvovaginal Signs and Symptoms
Not yet recruiting
Efficacy of Collagendep in Reducing Vulvar Dryness in Patients With Lichen Sclerosus Treated With Fat Grafting
Vulvar Lichen Sclerosus, Vulvar Atrophy
Recruiting
VALOR: Vaginal Atrophy & Long-term Observation of Recovery
Atrophic Vaginitis, Vaginal Atrophy

All Vulvar Atrophy trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1/2 Study of Intravaginal Tamoxifen (DARE-VVA1): Randomized, Double-blind, Placebo-controlled Study of Safety, Pharmacokinetics and Pharmacodynamics in Postmenopausal Participants With Moderate to Sever Vulvar and Vaginal Atrophy
ClinicalTrials.gov ID: NCT05378269
Acronym / sponsor ID: DARE-VVA1 / DARE-VVA-001
Conditions: Vulvar Atrophy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: Daré Bioscience, Inc.Industry (pharma, biotech, devices)
Study start: 22 Nov 2021 (actual)
Primary completion: 20 Dec 2022 (actual)
Study completion: 1 Mar 2023 (actual)
First posted: 18 May 2022 (actual)
Results: Posted 21 Oct 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of the study is to study the safety, PK and PD of Intravaginal Tamoxifen on postmenopausal women with vulvar vaginal atrophy.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Placebo	Placebo comparator	Other: PlaceboVaginal insert
DARE-VVA1 1mg	Experimental	Drug: Tamoxifenvaginal insert
DARE-VVA1 5mg	Experimental	Drug: Tamoxifenvaginal insert
DARE-VVA1 10mg	Experimental	Drug: Tamoxifenvaginal insert
DARE-VVA1 20mg	Experimental	Drug: Tamoxifenvaginal insert

Who may qualify

Ages: 40 to 75 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

1. Women aged 40-75 (inclusive).
2. Postmenopausal women with a body mass index between 18 and 34 kg/m2, inclusive.
3. Postmenopausal, defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels > 40 mIU/mL or 6 weeks post-surgical bilateral oophorectomy.
4. Have moderate to severe VVA as determined by self-assessment of the following symptoms (as none, mild, moderate, or severe), with at least 1 symptom reported as moderate or severe: vaginal dryness; vaginal and/or vulvar irritation/itching; dysuria; vaginal pain with sexual activity (dyspareunia); vaginal bleeding associated with sexual activity (presence versus absence).
5. Women who currently have vaginal intercourse or other sexual activity (masturbation, etc.) at least once a month (with or without a partner), or who had intercourse or other sexual activity at least once a month in the past, but later decreased sexual activity due to excessive pain or vaginal dryness. Participants must be willing to engage in vaginal intercourse or other sexual activity (masturbation, etc.) at least 1 time between Days 49-56 of the clinical study.

Key exclusion criteria (29 listed)

A history of or physical examination finding for any significant cardiovascular, renal, pulmonary, neurological and hepatic diseases preventing compliance with this study.
A medical history of or use of anticoagulant drugs to treat or prevent coagulopathies, thrombophilia or thromboembolic disease (deep vein thrombosis, pulmonary or systemic embolism, stroke, or transient ischemic attack).
Uncontrolled hypertension (either systolic > 180 mmHg or diastolic > 105 mmHg), treatment with Class 1 antiarrhythmics or digitalis, history of congestive heart failure (New York Heart Association [NYHA] > Class I), or myocardial infarction within 12 months.
Abnormal cervical screening test within 2 years of screening. Participant can have atypical squamous cells of undetermined significance if human papilloma virus-negative.
History of or current endometrial pathology: hyperplasia, carcinoma and/or polyp (prior history of a benign endometrial polyp with no current evidence of polyp is acceptable).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TamoxifenTamoxifen vaginal insert	Drug	DARE-VVA1 10mg, DARE-VVA1 1mg, DARE-VVA1 20mg, DARE-VVA1 5mg
PlaceboPlacebo vaginal insert	Other	Placebo

Primary outcome

Number of Subjects With Treatment Emergent Adverse Events
Time frame: 56 days
to evaluate the safety and tolerability of DARE-VVA1 by intravaginal administration
Concentration of Tamoxifen in Serial Plasma Collections (Cmax)
Time frame: 56 days
to determine the plasma concentrations of tamoxifen after intravaginal administration

3 secondary outcomes

Evaluation of Vaginal Cytology
Time frame: 56 days
Evaluation of Vaginal pH
Time frame: 56 days
Evaluation of Vaginal Cytology
Time frame: 56 days

Results and safety

Results posted to the registry on 21 Oct 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	4	3
DARE-VVA1 1mg	3	3
DARE-VVA1 5mg	4	2
DARE-VVA1 10mg	3	3
DARE-VVA1 20mg	3	3

Primary outcome: Number of Subjects With Treatment Emergent Adverse Events

Time frame: 56 days. Count of participants. Unit: Participants

Measure	Placebo n = 4	DARE-VVA1 1mg n = 3	DARE-VVA1 5mg n = 4	DARE-VVA1 10mg n = 3	DARE-VVA1 20mg n = 3
Value	3	2	4	3	3

Primary outcome: Concentration of Tamoxifen in Serial Plasma Collections (Cmax)

Time frame: 56 days. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Placebo n = 4	DARE-VVA1 1mg n = 3	DARE-VVA1 5mg n = 2	DARE-VVA1 10mg n = 3	DARE-VVA1 20mg n = 3
Value	0 (0)	0.181 (32.21)	1.93 (46.62)	3.29 (12.01)	5.50 (31.54)

Population analysed: Placebo users were not using Tamoxifen so a correlation between Tamoxifen and vaginal pH was not performed.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 56 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 4 (0%)	3 of 4 (75%)	0 of 4
DARE-VVA1 1mg	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
DARE-VVA1 5mg	0 of 4 (0%)	4 of 4 (100%)	0 of 4
DARE-VVA1 10mg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
DARE-VVA1 20mg	0 of 3 (0%)	3 of 3 (100%)	0 of 3

Limitations and caveats (from the sponsor): The study enrollment proved difficult and lead to small numbers of subjects analyzed per arm.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No. A decision has not yet been made on when or what IPD to share when available.

Related trials for Vulvar Atrophy

Not yet recruitingObservational study
Retrospective Cohort Study of Symptoms and Quality of Life in Women With Genitourinary Syndrome of Menopause.
Vulvar Atrophy, Vulvovaginal Signs and Symptoms
Active, not recruiting
Laser Vaginal Treatment for GSM
Menopausal Urethral Atrophy, Vulvar Atrophy
Recruiting
Changes in the Impact of Genitourinary Syndrome of Menopause With a Novel Nonhormonal Vulvovaginal Gel Assessed by PROMs.
Vulvar Atrophy, Vulvovaginal Signs and Symptoms
Not yet recruiting
Efficacy of Collagendep in Reducing Vulvar Dryness in Patients With Lichen Sclerosus Treated With Fat Grafting
Vulvar Lichen Sclerosus, Vulvar Atrophy
Recruiting
VALOR: Vaginal Atrophy & Long-term Observation of Recovery
Atrophic Vaginitis, Vaginal Atrophy

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tamoxifen in people with Vulvar Atrophy, run by Daré Bioscience, Inc. at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Treatment Emergent Adverse Events (time frame: 56 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05378269.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2024.