Trial of 4-Hydroxytamoxifen (4-OHT) Gel in Women Aimed at Reducing Dense Breast Tissue

NCT03199963 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: BHR-700-301
• Study Type: interventional
• Target: 223
• Locations: 3 countries
• Sites: 19

Brief 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.

Conditions

Mammographic Breast Density

Keywords

Mammographic; Breast; Density; BIRADS C or D

Outcome Measures

Primary Outcomes (1)

• The Percent Reduction of Mammographic Dense Breast (MBD) Tissue on a Follow-up Mammogram Compared to the Baseline Mammogram After 52 Weeks of Treatment.

  Percent MBD at screening compared to percent MBD after 52 weeks of treatment with either BHR-700 or Placebo.

  Blinded Phase: Baseline; Week 52

Secondary Outcomes (6)

• Number and Severity of Adverse Events (AEs)

  Blinded Phase: Baseline; Weeks 13, 26, 39, 52/EOS and Open Label Phase

• Change in Serum Concentration of Sex Hormone Binding Globulin (SHBG) From Baseline to Week 52/End of Study (EOS)

  Blinded Phase: Baseline; Week 52/EOS

• Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL).

  Blinded Phase: Baseline; Weeks 26, 52/EOS.

• Change in Serum Concentration of Select Bone Biomarkers: Bone Specific Alkaline Phosphatase (BSAP) (U/L)

  Blinded Phase: Baseline; Week 52/EOS

• Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit

  Blinded Phase: Weeks 13, 26, 52/EOS

Study Arms (2)

BHR-700 (0.2% 4-OHT gel)

EXPERIMENTAL

The gel formulation contains 2 mg/mL 4-OH tamoxifen (0.2%) in a clear, colorless, absorptive hydro-alcoholic gel base formulated to provide continuous release of 4-OH tamoxifen. A total of 8 mg/day (4 mg/breast) of 4-OH tamoxifen will be administered daily for 52 weeks.

Drug: 4-OH tamoxifen

Matching Placebo Gel

PLACEBO COMPARATOR

An absorptive hydroalcoholic gel preparation of the same ingredients as BHR-700, but without 4-OHT.

Drug: Placebo

Interventions

4-OH tamoxifen DRUG

4-Hydroxytamoxifen (afimoxifene) gel

Also known as: 4-OHT

BHR-700 (0.2% 4-OHT gel)

Placebo DRUG

An absorptive hydroalcoholic gel preparation of the same ingredients as BHR-700, but without 4-OHT.

Matching Placebo Gel

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Participants may not be receiving treatment with any investigational drug or biologic within 30 days of randomization or at any time during the study.
• Women with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Tamoxifen.
• 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.
• Pregnancy (independent of outcome) and/or lactation within 1 year prior to the screening mammogram.
• Women with previous history of cancer (including invasive or intra-ductal breast cancer) except for non-melanoma skin cancer.
• Women who have had a prior mastectomy (unilateral or bilateral), segmental mastectomy, reduction mammoplasty or breast augmentation including implants.
• Women with surgical breast biopsy(s) performed within 3 years or core biopsy(s) performed within 1 year prior to the screening mammogram.
• 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.
• 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.
• Women with active liver disease or thromboembolic disorder.
• 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.
• 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.
• Women who have received treatment with Selective Estrogen Receptor Modulators (SERMs) (e.g. tamoxifen, raloxifene) or aromatase inhibitors
• 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.
• 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.

Sponsors & Collaborators

• BHR Pharma, LLC: lead

Study Sites (19)

Mesa Obstetricians and Gynecologists/Cactus Clinical Research

Mesa, Arizona, 85209, United States

Location

Visions Clinical Research

Tucson, Arizona, 85712, United States

Location

United Clinical Research

Beverly Hills, California, 90211, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

USC-Keck Medical Center

Los Angeles, California, 90033, United States

Location

South Florida Medical Research

Aventura, Florida, 33180, United States

Location

Lake OB-GYN Associates of Mid-Florida

Leesburg, Florida, 34748, United States

Location

Physician Care Clinical Research, LLC

Sarasota, Florida, 34239, United States

Location

Affiliated Clinical Research, Inc.

Las Vegas, Nevada, 89113, United States

Location

Center for Women's Health and Wellness

Plainsboro, New Jersey, 08536, United States

Location

Bosque Women Care/Cactus Clinical Research

Albuquerque, New Mexico, 87109, United States

Location

Carolina Women's Research and Wellness Center

Durham, North Carolina, 27713, United States

Location

Aventiv Research, Inc.

Columbus, Ohio, 43213, United States

Location

Coastal Carolina Research Center, Inc.

Mt. Pleasant, South Carolina, 29464, United States

Location

University of Virginia Medical Park Northridge

Charlottesville, Virginia, 22903, United States

Location

Overlake Internal Medicine Associates, PS

Bellevue, Washington, 98004, United States

Location

Dedicated Women's Health Specialists

Puyallup, Washington, 98372, United States

Location

Private Practice - Gynecology

Frankfurt am Main, Hesse, 60322, Germany

Location

Instituto Palacios Salud de La Mujer

Madrid, 28009, Spain

Location

MeSH Terms

Interventions

4,17 beta-dihydroxy-4-androstene-3-one

Limitations and Caveats

Other (Not Including Serious) Adverse Events entries are based on number of subject in the intention-to-treat (ITT) population (blinded phase, safety population). Includes all adverse events reported.

Results Point of Contact

• Title: Global Chief Medical Officer
• Organization: Besins Healthcare Ireland Ltd

clinicaldevelopment@besins-healthcare.com

+353 87 1039215

Study Officials

• Chief Medical Officer

  BHR Pharma, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double blind, placebo controlled

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: June 27, 2017
• Study Start: August 21, 2017
• Primary Completion: January 14, 2019
• Study Completion: April 23, 2019
• Last Updated: July 26, 2022
• Results First Posted: November 17, 2021

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); ES (1); US (17)