Breast tissue density in women with BI-RADS Breast Density Categories C to D MedDRA version: 20.0 Level: LLT Classification code 10065307 Term: Breast density increased System Organ Class: 100000004848
Conditions
Interventions
Product Name: BHR-700
Product Code: FP-241
Pharmaceutical Form: Gel
INN or Proposed INN: Afimoxifene
CAS Number: 68392-35-8
Sponsors
BHR Pharma, LLC
Eligibility
Sex/Gender
All
Inclusion 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 woman is of childbearing potential, she must have a documented negative urine pregnancy test at 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Participants may not be receiving treatment with any investigational drug or investigational 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 IP. 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, raloxifen) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 using the Food and Drug Administration (FDA)-cleared Cumulus 2D software.;Primary end point(s): The percentage reduction of mammographic breast tissue density on a follow-up mammogram compared to the baseline mammogram after 52 weeks of treatment.; Secondary Objective: Incidence and severity of adverse events (AEs) with special attention given to uterine abnormalities, cardiovascular events, thromboembolic events, and incidence of vasomotor symptoms (“hot flush”). Change in serum concentration of sex hormone binding globulin (SHBG). Change in serum concentration of: cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Change in serum concentration of Protein C-activity, Protein Sactivity, Antithrombin 111 antigen, and Activated Protein C resistance (APCR). Change in serum concentration of select bone biomarkers CTx and BSAP. Plasma concentrations of the E and Z isomers of 4-OHT. ;Timepoint(s) of evaluation of this end point: 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): #1 Incidence and severity of adverse events (AEs) with special attention given to uterine abnormalities, cardiovascular events, thromboembolic events, and incidence of vasomotor symptoms (“hot flush”). #2 Change in serum concentration of sex hormone binding globulin (SHBG). #3 Change in serum concentration of: cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). #4 Change in serum concentration of Protein C-activity, Protein Sactivity, Antithrombin 111 antigen, and Activated Protein C resistance (APCR). #5 Change in serum concentration of select bone biomarkers CTx and BSAP. #6 Plasma concentrations of the E and Z isomers of 4-OHT. ; Timepoint(s) of evaluation of this end point: Secondary end point #1 Blinded Phase Week 13, Week 26, Week 39, Week 52 Open-Label Phase Week 13, Week 26, Week 39, Week 52 Secondary end point #2 Blinded Phase Week 52 Open-Label Phase Week 52 Secondary end point #3 Blinded Phase Week 26, Week 52 Open-Label Phase Week 26, Week 52 Secondary end point #4 Blinded Phase Week 26, Week 52 Open-Label Phase Week 26, Week 52 Secondary end point #5 Blinded Phase Week 52 Open-Label Phase Week 52 Secondary end point #6 Blinded Phase Week 13, Week 26, Week 52 Open-Label Phase Week 26, Week 52 | — |
Countries
Germany, Spain, United States
Contacts
Public ContactClinical Trials Information
FGK Clinical Research GmbH
Outcome results
None listed