Mammographic Breast Density
Conditions
Keywords
Mammographic, Breast, Density, BIRADS C or D
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.
Detailed description
This is a randomized, double blind, placebo-controlled study. Subjects will have been assessed as having mammographically dense breast (heterogeneously dense (C) or extremely dense (D), based on the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BIRADS©) fifth edition classification) for eligibility. Approximately 330 subjects will be enrolled at approximately 25 sites in the US and the European Union. Subjects who give informed consent will be stratified, based on whether they are pre/peri or post-menopausal and randomized 2:1 within those groups to receive either 8 mg/day (4 mg/breast) 4-OHT or matching placebo for up to 52 weeks. Subjects will apply the investigational gel to both breasts once per day until they have completed 52 weeks of study drug administration. There will be, in addition, an optional 52 weeks of open-label treatment for those subjects who choose to continue treatment. Subjects will capture daily gel administration in a diary to monitor compliance. While on treatment, subjects will return to the clinic for study assessments, a review of adverse events (AEs) and to re-supply study gel at 13, 26, 39, weeks and at 52 weeks for those subjects who have agreed to take part in the open-label phase of the study. During the study, in a case of significant changes in bleeding pattern or other signs/symptoms which could be related to endometrial pathology, the Investigator will perform a uterine ultrasound followed by an endometrial biopsy if indicated. Open-Label Treatment Phase Secondary Outcome Measures: • Comparison of breast density measurements (Cumulus and Volpara) • Laboratory parameters will be summarized in a descriptive fashion. • Incidence and severity of AEs will be compared between BHR-700 gel and placebo.
Interventions
DRUG4-OH tamoxifen
4-Hydroxytamoxifen (afimoxifene) gel
DRUGPlacebo
An absorptive hydroalcoholic gel preparation of the same ingredients as BHR-700, but without 4-OHT.
Sponsors
BHR Pharma, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double blind, placebo controlled
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percent Reduction of Mammographic Dense Breast (MBD) Tissue on a Follow-up Mammogram Compared to the Baseline Mammogram After 52 Weeks of Treatment. | Blinded Phase: Baseline; Week 52 | Percent MBD at screening compared to percent MBD after 52 weeks of treatment with either BHR-700 or Placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | SHBG levels at baseline will be compared to levels at 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. | Lipid levels at baseline will be compared to levels measured at time-points in the study |
| Number and Severity of Adverse Events (AEs) | Blinded Phase: Baseline; Weeks 13, 26, 39, 52/EOS and Open Label Phase | AEs monitored and reported throughout study |
| 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 | Blood samples will be taken to measure plasma concentrations of 4-OHT at time-points in the study |
| Change in Serum Concentration of Select Bone Biomarkers:Type I Collagen C-Telopeptides (CTx) (pg/mL) | Blinded Phase: Baseline; Week 52/EOS | Bone biomarker levels (CTx) at baseline will be compared to levels measured at Week 52. |
| Change in Serum Concentration of Select Bone Biomarkers: Bone Specific Alkaline Phosphatase (BSAP) (U/L) | Blinded Phase: Baseline; Week 52/EOS | Bone biomarker levels (BSAP) at baseline will be compared to levels measured at Week 52. |
Countries
Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BHR-700 (0.2% 4-OHT Gel) 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.
4-OH tamoxifen: 4-Hydroxytamoxifen (afimoxifene) gel | 149 |
| Matching Placebo Gel An absorptive hydroalcoholic gel preparation of the same ingredients as BHR-700, but without 4-OHT.
Placebo: An absorptive hydroalcoholic gel preparation of the same ingredients as BHR-700, but without 4-OHT. | 74 |
| Total | 223 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Phase - Overall Study | Adverse Event | 10 | 5 |
| Blinded Phase - Overall Study | Lost to Follow-up | 9 | 2 |
| Blinded Phase - Overall Study | Study was terminated early by the Sponsor for administrative reasons. | 109 | 54 |
| Blinded Phase - Overall Study | Withdrawal by Subject | 5 | 5 |
| Optional Open-Label Phase - BHR-700 | Adverse Event | 0 | 1 |
| Optional Open-Label Phase - BHR-700 | Study terminated early by Sponsor for administrative reasons; data contribution was negligible. | 7 | 5 |
Baseline characteristics
| Characteristic | BHR-700 (0.2% 4-OHT Gel) | Matching Placebo Gel | Total |
|---|---|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 9.23 | 56.2 years STANDARD_DEVIATION 9.63 | 54.9 years STANDARD_DEVIATION 9.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 7 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 132 Participants | 65 Participants | 197 Participants |
| Region of Enrollment Germany | 3 participants | 1 participants | 4 participants |
| Region of Enrollment Spain | 6 participants | 2 participants | 8 participants |
| Region of Enrollment United States | 140 participants | 71 participants | 211 participants |
| Sex: Female, Male Female | 149 Participants | 74 Participants | 223 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 149 | 0 / 73 | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 71 / 149 | 43 / 73 | 3 / 7 | 4 / 6 |
| serious Total, serious adverse events | 5 / 149 | 0 / 73 | 1 / 7 | 0 / 6 |
Outcome results
Primary
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.
Time frame: Blinded Phase: Baseline; Week 52
Population: Study was terminated early for administrative and not safety reasons; an abbreviated clinical study report was prepared and results were limited to safety parameters only. This outcome was not collected and therefore cannot be reported.
Secondary
Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL).
Lipid levels at baseline will be compared to levels measured at time-points in the study
Time frame: Blinded Phase: Baseline; Weeks 26, 52/EOS.
Population: Study was terminated early for administrative and not safety reasons; an abbreviated clinical study report was prepared and results were limited to safety and pharmacokinetic (PK)/pharmacodynamic (PD) parameters only. Of all subjects that attended the Week 52/End of Study visit, only 24 subjects completed 52 weeks of treatment. All other subjects stopped treatment at various timepoints before the 52 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Cholesterol (mmol/L) - Change from Baseline to Week 26 | -0.1 mmol/L | Standard Deviation 0.6 |
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS | 0.1 mmol/L | Standard Deviation 0.7 |
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Triglycerides (mmol/L) - Change from Baseline to Week 26 | -0.2 mmol/L | Standard Deviation 1.2 |
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Triglycerides (mmol/L) - Change from Baseline to Week 52/EOS | -0.1 mmol/L | Standard Deviation 0.8 |
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | HDL Cholesterol (mmol/L) - Change from Baseline to Week 26 | -0.0 mmol/L | Standard Deviation 0.3 |
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | HDL Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS | 0.0 mmol/L | Standard Deviation 0.2 |
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | LDL Cholesterol (mmol/L) - Change from Baseline to Week 26 | 0.0 mmol/L | Standard Deviation 0.6 |
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | LDL Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS | 0.1 mmol/L | Standard Deviation 0.5 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | LDL Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS | -0.0 mmol/L | Standard Deviation 0.7 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Cholesterol (mmol/L) - Change from Baseline to Week 26 | -0.2 mmol/L | Standard Deviation 0.7 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | HDL Cholesterol (mmol/L) - Change from Baseline to Week 26 | 0.0 mmol/L | Standard Deviation 0.2 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS | 0.0 mmol/L | Standard Deviation 0.7 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | LDL Cholesterol (mmol/L) - Change from Baseline to Week 26 | -0.1 mmol/L | Standard Deviation 0.7 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Triglycerides (mmol/L) - Change from Baseline to Week 26 | -0.2 mmol/L | Standard Deviation 0.6 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | HDL Cholesterol (mmol/L) - Change from Baseline to Week 52/EOS | 0.0 mmol/L | Standard Deviation 0.3 |
| Matching Placebo Gel | Change in Serum Concentration of: Cholesterol, Triglycerides, High-density Lipoprotein (HDL), and Low-density Lipoprotein (LDL). | Triglycerides (mmol/L) - Change from Baseline to Week 52/EOS | 0.0 mmol/L | Standard Deviation 0.8 |
Secondary
Change in Serum Concentration of Select Bone Biomarkers: Bone Specific Alkaline Phosphatase (BSAP) (U/L)
Bone biomarker levels (BSAP) at baseline will be compared to levels measured at Week 52.
Time frame: Blinded Phase: Baseline; Week 52/EOS
Population: 133 participants in the BHR-700 arm and 65 in the placebo arm were included at baseline. Data from 97 BHR-700 and 48 placebo participants are reported at Week 52/EOS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of Select Bone Biomarkers: Bone Specific Alkaline Phosphatase (BSAP) (U/L) | 1.0 BSAP in U/L | Standard Deviation 4.1 |
| Matching Placebo Gel | Change in Serum Concentration of Select Bone Biomarkers: Bone Specific Alkaline Phosphatase (BSAP) (U/L) | 0.7 BSAP in U/L | Standard Deviation 3.3 |
Secondary
Change in Serum Concentration of Select Bone Biomarkers:Type I Collagen C-Telopeptides (CTx) (pg/mL)
Bone biomarker levels (CTx) at baseline will be compared to levels measured at Week 52.
Time frame: Blinded Phase: Baseline; Week 52/EOS
Population: 133 participants in the BHR-700 arm and 65 in the placebo arm were included at baseline. Data from 97 BHR-700 and 48 placebo participants are reported at Week 52/EOS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of Select Bone Biomarkers:Type I Collagen C-Telopeptides (CTx) (pg/mL) | -19.6 pg/mL | Standard Deviation 162 |
| Matching Placebo Gel | Change in Serum Concentration of Select Bone Biomarkers:Type I Collagen C-Telopeptides (CTx) (pg/mL) | 3.7 pg/mL | Standard Deviation 155.5 |
Secondary
Change in Serum Concentration of Sex Hormone Binding Globulin (SHBG) From Baseline to Week 52/End of Study (EOS)
SHBG levels at baseline will be compared to levels at Week 52/EOS
Time frame: Blinded Phase: Baseline; Week 52/EOS
Population: This parameter captures data from Week 52 or End of Study for subjects who stopped treatment at various timepoints before the 52 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BHR-700 (0.2% 4-OHT Gel) | Change in Serum Concentration of Sex Hormone Binding Globulin (SHBG) From Baseline to Week 52/End of Study (EOS) | 0.1 mg/L | Standard Deviation 1.6 |
| Matching Placebo Gel | Change in Serum Concentration of Sex Hormone Binding Globulin (SHBG) From Baseline to Week 52/End of Study (EOS) | 0.3 mg/L | Standard Deviation 1.6 |
Secondary
Number and Severity of Adverse Events (AEs)
AEs monitored and reported throughout study
Time frame: Blinded Phase: Baseline; Weeks 13, 26, 39, 52/EOS and Open Label Phase
Population: A total of 223 subjects were enrolled in this study; 222 subjects were randomized to the study treatment and received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BHR-700 (0.2% 4-OHT Gel) | Number and Severity of Adverse Events (AEs) | Subjects with at least one mild AE | 56 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number and Severity of Adverse Events (AEs) | Subjects with at least one severe AE | 8 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number and Severity of Adverse Events (AEs) | Subjects with at least one moderate AE | 49 Participants |
| Matching Placebo Gel | Number and Severity of Adverse Events (AEs) | Subjects with at least one mild AE | 31 Participants |
| Matching Placebo Gel | Number and Severity of Adverse Events (AEs) | Subjects with at least one severe AE | 4 Participants |
| Matching Placebo Gel | Number and Severity of Adverse Events (AEs) | Subjects with at least one moderate AE | 29 Participants |
| Open Label BHR-700 (0.2% 4-OHT Gel) Following BHR-700 in Blinded Phase | Number and Severity of Adverse Events (AEs) | Subjects with at least one moderate AE | 2 Participants |
| Open Label BHR-700 (0.2% 4-OHT Gel) Following BHR-700 in Blinded Phase | Number and Severity of Adverse Events (AEs) | Subjects with at least one mild AE | 2 Participants |
| Open Label BHR-700 (0.2% 4-OHT Gel) Following BHR-700 in Blinded Phase | Number and Severity of Adverse Events (AEs) | Subjects with at least one severe AE | 1 Participants |
| Open Label BHR-700 (0.2% 4-OHT Gel) Following Placebo in Blinded Phase | Number and Severity of Adverse Events (AEs) | Subjects with at least one mild AE | 1 Participants |
| Open Label BHR-700 (0.2% 4-OHT Gel) Following Placebo in Blinded Phase | Number and Severity of Adverse Events (AEs) | Subjects with at least one severe AE | 0 Participants |
| Open Label BHR-700 (0.2% 4-OHT Gel) Following Placebo in Blinded Phase | Number and Severity of Adverse Events (AEs) | Subjects with at least one moderate AE | 1 Participants |
Secondary
Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit
Blood samples will be taken to measure plasma concentrations of 4-OHT at time-points in the study
Time frame: Blinded Phase: Weeks 13, 26, 52/EOS
Population: Concentrations measured only in participants who received BHR-700. Of all subjects that attended the Week 52/End of Study visit, only 24 subjects completed 52 weeks of treatment. All other subjects stopped treatment at various timepoints before the 52 weeks.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 13 E-4-OHT | Participants with measurable concentration | 12 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 13 E-4-OHT | Participants with concentration below lower limit of quantitation | 128 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 26 E-4-OHT | Participants with measurable concentration | 7 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 26 E-4-OHT | Participants with concentration below lower limit of quantitation | 88 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 52/EOS E-4-OHT | Participants with measurable concentration | 0 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 52/EOS E-4-OHT | Participants with concentration below lower limit of quantitation | 179 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 13 Z-4-OHT | Participants with measurable concentration | 75 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 13 Z-4-OHT | Participants with concentration below lower limit of quantitation | 65 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 26 Z-4-OHT | Participants with measurable concentration | 48 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 26 Z-4-OHT | Participants with concentration below lower limit of quantitation | 47 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 52/EOS Z-4-OHT | Participants with measurable concentration | 16 Participants |
| BHR-700 (0.2% 4-OHT Gel) | Number of Participants With Measurable Plasma Concentrations of the E and Z Isomers of 4-OHT by Visit | Week 52/EOS Z-4-OHT | Participants with concentration below lower limit of quantitation | 163 Participants |