Trial of 4-Hydroxytamoxifen (4-OHT) Gel in Women Aimed at Reducing Dense Breast Tissue
Condition: Mammographic Breast Density
Intervention: 4-OH tamoxifen; Placebo
Intervention description: 4-Hydroxytamoxifen (afimoxifene) gel; An absorptive hydroalcoholic gel preparation of the same ingredients as BHR-700, but without 4-OHT.
Intervention MeSH terms: Tamoxifen; Afimoxifene
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double blind, placebo controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 223.0
Sex: Female
Minimum age: 35 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Mammographic; Breast; Density; BIRADS C or D

Summary:

      A study to determine the efficacy of 8 mg/day (4 mg/breast) of BHR-700 gel compared to
      placebo for reducing breast tissue density in women identified as having dense breast tissue
      upon analysis of screening mammography. The Primary Study Endpoint being the percent
      reduction of mammographic breast tissue density on a follow-up mammogram compared to the
      baseline mammogram after 52 weeks of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy women age 35 - 75 years with either heterogeneously dense (C) or extremely
             dense (D), breast tissue on 2D mammography, based on American College of Radiology
             (ACR) Breast Imaging-Reporting and Data System (BI-RADS©) fifth edition
             classification) in either breast within 3 months prior to randomization. Mammogram
             with BI-RADS final assessment category 1 or 2 (negative or benign findings).

          2. If the participant is of childbearing potential, she must have a documented negative
             urine pregnancy test at the time of screening and randomization and no plans to become
             pregnant for the duration of study participation.

          3. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Participants may not be receiving treatment with any investigational drug or biologic
             within 30 days of randomization or at any time during the study.

          2. Women with a history of allergic reactions attributed to compounds of similar chemical
             or biologic composition to Tamoxifen.

          3. Pregnant women are excluded from this study because the effects of 4-OHT gel on the
             developing human fetus at the recommended dose and route are unknown.

          4. Pregnancy (independent of outcome) and/or lactation within 1 year prior to the
             screening mammogram.

          5. Women with previous history of cancer (including invasive or intra-ductal breast
             cancer) except for non-melanoma skin cancer.

          6. Women who have had a prior mastectomy (unilateral or bilateral), segmental mastectomy,
             reduction mammoplasty or breast augmentation including implants.

          7. Women with surgical breast biopsy(s) performed within 3 years or core biopsy(s)
             performed within 1 year prior to the screening mammogram.

          8. Women with an abnormal mammogram (BI-RADS final assessment category 3-probably benign,
             4-suspicious, or 5-malignant findings). Women with BI-RADS 0 assessment (needs
             additional imaging evaluation) that are subsequently found to have negative (BI-RADS
             1) or benign findings (BI-RADS 2), are NOT excluded.

          9. Women with only synthetic 2D mammograms generated from 3D (tomosynthesis) are excluded
             as breast density measurements are not yet validated for synthetic mammograms. Women
             with combination 2D+3D mammograms are not excluded.

         10. Women with active liver disease or thromboembolic disorder.

         11. Women with skin conditions such as psoriasis, fungal infections, keloids etc., or
             tattoos and/or piercings, which in the opinion of the Investigator, would interfere
             with absorption of the Investigational Product.

         12. Women who have had an abnormal gynecology exam within the last three years with
             clinically significant findings, such as secondary dysmenorrhea, polyps, or atypia,
             which in the opinion of the Investigator would interfere with the study.

         13. Women who have received treatment with Selective Estrogen Receptor Modulators (SERMs)
             (e.g. tamoxifen, raloxifene) or aromatase inhibitors

         14. Women taking estrogen containing contraceptives or Hormone Replacement Therapy (HRT)
             must discontinue the treatment a minimum of 6 months prior to the screening mammogram.
             Progestin only contraceptives are permitted.

         15. Women with a concurrent illness, disease or condition that, in the opinion of the
             Investigator, would limit their compliance with study requirements or place them at
             additional risk.