Study of Intravaginal Tamoxifen in PostMenopausal Women With VVA

NCT05378269 | Completed Phase 1 Results

• 1 other identifier: DARE-VVA-001
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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

Outcome Measures

Primary Outcomes (2)

• Number of Subjects With Treatment Emergent Adverse Events

  to evaluate the safety and tolerability of DARE-VVA1 by intravaginal administration

  56 days

• Concentration of Tamoxifen in Serial Plasma Collections (Cmax)

  to determine the plasma concentrations of tamoxifen after intravaginal administration

  56 days

Secondary Outcomes (3)

• Evaluation of Vaginal Cytology

  56 days

• Evaluation of Vaginal pH

  56 days

• Evaluation of Vaginal Cytology

  56 days

Other Outcomes (1)

• Collection of Menopause-specific Quality of Life (MENQOL) Questionnaire

  56 days

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Vaginal insert

Other: Placebo

DARE-VVA1 1mg

EXPERIMENTAL

vaginal insert

Drug: Tamoxifen

DARE-VVA1 5mg

EXPERIMENTAL

vaginal insert

Drug: Tamoxifen

DARE-VVA1 10mg

EXPERIMENTAL

vaginal insert

Drug: Tamoxifen

DARE-VVA1 20mg

EXPERIMENTAL

vaginal insert

Drug: Tamoxifen

Interventions

Tamoxifen DRUG

Tamoxifen vaginal insert

DARE-VVA1 10mg; DARE-VVA1 1mg; DARE-VVA1 20mg; DARE-VVA1 5mg

Placebo OTHER

Placebo vaginal insert

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Women aged 40-75 (inclusive).
• \. Postmenopausal women with a body mass index between 18 and 34 kg/m2, inclusive.
• \. 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.
• \. 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).
• \. 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.
• \. 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).
• \. Have an intact uterus and no prior history of endometrial ablation.
• \. Vaginal cellular cytology with ≤ 5% superficial cells.
• \. Vaginal pH \> 5 at Screening Visit.
• \. Endometrial thickness ≤ 4 mm on transvaginal ultrasound.
• \. Current on all recommended screening and management requirements for cervical cancer.
• \. Normal mammogram report within 2 years of screening.
• \. Normal manual breast examination by investigator at baseline.
• \. 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.
• \. Normal 12-lead electrocardiogram (ECG).

You may not qualify if:

• 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.
• 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.

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

MeSH Terms

Interventions

Tamoxifen

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

The study enrollment proved difficult and lead to small numbers of subjects analyzed per arm.

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 18, 2022
• Study Start: November 22, 2021
• Primary Completion: December 20, 2022
• Study Completion: March 1, 2023
• Last Updated: October 21, 2024
• Results First Posted: October 21, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)