Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Progesterone

Progestins

Hormones

Hormone Antagonists

Patients receive telapristone acetate orally once daily for 2-10 weeks and then undergo surgical resection.

Patients receive placebo orally once daily for 2-10 weeks and then undergo surgical resection.

telapristone acetate

placebo

therapeutic conventional surgery

laboratory biomarker analysis

questionnaire administration

Seema Khan, MD

The purpose of this study is to determine whether or not the medication that blocks the effects of the hormone progesterone (CDB-4124 or Proellex) will decrease the growth rate of breast cancer cells as compared to a placebo. CDB-4124 (also called Proellex) is a medication that works against the hormone, progesterone. The researchers in this study would like to compare changes in breast cancer cells of women who have taken CDB-4124 prior to surgery to those from women who have taken a placebo pill prior to surgery.

PRIMARY OBJECTIVES:

I. To test the hypothesis that treatment with the selective progesterone receptor modulator (SPRM) CDB-4124 (telapristone acetate) will have an anti-tumor effect in women with early-stage breast cancer, defined as a significant decrease in tumor proliferation (Ki67 labeling index).

SECONDARY OBJECTIVES:

I. Measure changes in apoptosis using IHC (cleaved caspase 3 or TUNEL). II. Measure changes in blood estradiol and progesterone levels. III. Compare the breast tissue concentrations of CDB-4124 and its metabolite (CDB4453) to plasma concentrations at the end of therapy.

IV. Assess adverse events.

TERTIARY OBJECTIVES:

I. Measure protein expression of related targets (including estrogen receptor alpha (ERA), estrogen receptor beta (ERB), progesterone receptor isoforms progesterone receptor alpha \[PRA\], progesterone receptor beta \[PRB\], tumor necrosis factor receptor superfamily, member 11a, NFKB activator \[RANK\], tumor necrosis factor (ligand) superfamily, member 11 \[RANKL\], and either cyclin-dependent kinase 2 \[cdk2\] or cyclin-dependent kinase 4 \[cdk4\],) using IHC at baseline and after treatment.

II. Perform ribonucleic acid (RNA) microarray analysis comparing tumors and normal tissue from the intervention and control groups.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive telapristone acetate orally (PO) once daily (QD) for 2-10 weeks and then undergo surgical resection.

ARM II: Patients receive placebo orally once daily for 2-10 weeks and then undergo surgical resection.

After completion of study treatment, patients are followed up for 1 month.

Oral CDB-4124 vs. Placebo in Stage I-II Primary Breast Cancer

Presurgical Phase IIB Trial of Oral CDB-4124 vs. Placebo in Women With Stage I-II Primary Breast Cancer

Measurement of protein expression in related biomarkers will be taken, from biopsy tissue, at baseline and on the day of surgery.

RNA microarray analysis will be conducted at baseline and on the day of surgery comparing tumors as well as normal tissue from the patients receiving treatment drug and patients receiving placebo.

Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery to measure if there is a decrease in tumor growth.

Using tissue samples, the expression of apoptosis marker will be measured in the intervention group and compared to the placebo group at the time of surgery.

Serum estradiol and progesterone levels will be measured at baseline and at the time of surgery to assess any changes.

Breast tissue concentrations of study drug will be measured in tumor and normal tissue adjacent to the tumor at the time of surgery. Plasma concentrations of drug will also be measured for comparison to see if there is a correlation between tissue concentration of drug and the reduction in tumor growth after treatment.

Adverse events will be assessed throughout treatment by evaluating liver and renal function tests that will be performed at baseline, week 4, and at the post-intervention (pre-surgical) visit. Symptom measurements (using a questionnaire) will be performed at baseline, post-intervention (pre-surgical), and 1 month following surgery.

Breast Cancer Research Foundation

Repros Therapeutics Inc.

Northwestern University

Principal Investigator

Leiomyoma

Myofibroma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

Following the baseline assessment no treatment period, matching placebo, orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the off drug interval (ODI).

Following the baseline assessment no treatment period, telapristone acetate 6 milligrams (mg), orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the ODI.

Following the baseline assessment no treatment period, telapristone acetate 12 mg, orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the ODI.

Telapristone acetate, orally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

Telapristone Acetate

Matching placebo, orally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

Placebo

Anna Chan

The primary objective of this study is to determine the safety and efficacy of two oral doses of Proellex administered for up to 2 courses of treatment (18 weeks each), each separated by an Off-Drug Interval (ODI), to premenopausal women with symptomatic uterine fibroids.

A Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

A Phase 2, Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

Amenorrhea was defined as no bleeding intensity score greater than 1 using the Daily Diary Card during the 28 days leading up to the last day of dosing at Week 18. Bleeding intensity was graded on a 5-point scale where: 0=no bleeding to 4=heavy bleeding.

Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Participants recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Pictorial scores range from score 1 for slightly stained tampon/towel, 5 for a partially stained tampon/towel, 10 for a completely saturated tampon, 20 for a completely saturated towel, and 5 for each episode of flooding and for each blood clot larger than a quarter in size. Total score can range from 0 (no bleeding) to \>500. Higher scores indicate more bleeding. Lower scores indicate less bleeding. A negative change from Baseline indicates improvement (reduction in bleeding).

Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Participants recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Pictorial scores range from score 1 for slightly stained tampon/towel, 5 for a partially stained tampon/towel, 10 for a completely saturated tampon, 20 for a completely saturated towel, and 5 for each episode of flooding and for each blood clot larger than a quarter in size. Total score can range from 0 (no bleeding) to \>500. Higher scores indicate more bleeding. Lower scores indicate less bleeding. A negative percentage change from Baseline indicates improvement (reduction in bleeding).

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. Each question was answered on a 5-point scale where 1=Not at all to 5=A very great deal. The sum of total scores was transformed to a range of 0=no symptoms (best) to 100=most severe symptoms (worst). A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 1: During the previous 3 months how distressed were you by "heavy bleeding during your menstrual period"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 2: During the previous 3 months how distressed were you by "passing blood clots during your menstrual period"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 3: During the previous 3 months how distressed were you by "fluctuation in the duration of your menstrual period compared to your previous cycle"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 4: During the previous 3 months how distressed were you by "fluctuation in the length of your monthly cycle compared to your previous cycles"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 5: During the previous 3 months how distressed were you by "feeling tightness or pressure in your pelvic area"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 6: During the previous 3 months how distressed were you by "frequent urination during the daytime hours"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 7: During the previous 3 months how distressed were you by "frequent nighttime urination"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 8: During the previous 3 months how distressed were you by "feeling fatigued"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative percentage change from Baseline indicates improvement.

Safety population consisted of all participants who were randomized, received study drug, and had some post-baseline safety data.

Following the baseline assessment no treatment period, telapristone acetate 6 milligrams (mg), orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the off drug interval (ODI).

Telapristone Acetate 6 mg

Telapristone Acetate 12 mg

Following the baseline assessment no treatment period, matching placebo, orally, once daily for 18 weeks (Treatment Course 1) and repeated for an additional 18 weeks (Treatment Course 2) following the ODI.

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Therapeutic Area, Head

Intent-to-treat (ITT) population consisted of all participants who were randomized and received study drug.

Percentage of Participants in Amenorrhea at the End of Treatment Course 1

ITT population consisted of all participants who were randomized and received study drug.

Percentage of Participants in Amenorrhea at the End of Treatment Course 2

Baseline

Change from Baseline (CFB) to Week 18 Course 1

CFB to ODI Course 1

CFB to Week 18 Course 2

CFB to Course 2 Week 28 FU

ITT population consisted of all participants who were randomized and received study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

Change in Pictorial Blood Loss Assessment Chart (PBAC) Score From Baseline to the End of Treatment Courses 1 and 2, ODI Course 1 and the Course 2 Week 28 Follow-up (FU) Visit

Percentage CFB to Week 18 Course 1

Percentage CFB to ODI Course 1

Percentage CFB to Week 18 Course 2

Percentage CFB to Course 2 Week 28 FU

Percentage Change in PBAC Score From Baseline to the End of Treatment Courses 1 and 2, ODI Course 1 and the Course 2 Week 28 FU Visit

Percentage CFB to On-Drug Course 2

Percentage CFB to Course 2 Week 24 FU

Percentage Change in Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 1 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 2 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 3 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 4 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 5 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 6 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 7 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 8 From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Week 24 FU Visit

Percentage CFB to Course 2 Off-drug

Percentage Change in Total Uterine Fibroid Volume From Baseline to the End of Treatment Courses 1 and 2, On-drug Course 2 and the Course 2 Off-drug

Treatment Course 1

Treatment Course 2

Fibroma

Following the baseline assessment no treatment period, matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

Following the baseline assessment no treatment period, telapristone acetate 6 milligrams (mg), vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

Following the baseline assessment no treatment period, telapristone acetate 12mg, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

Matching placebo, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

Telapristone acetate, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

The primary objective of this study is to determine the safety and efficacy of two vaginal doses of Proellex® administered for up to 2 courses of treatment (18 weeks each), each separated by an Off-Drug Interval (ODI), to premenopausal women with symptomatic uterine fibroids.

Safety and Efficacy of Telapristone Acetate (Proellex®) Administered Vaginally for the Treatment of Uterine Fibroids

A Phase 2, Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Vaginally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score \>1. Participants were provided with a daily diary and Pictorial Blood Loss Assessment Chart (PBAC) to record information about the menstrual blood loss (MBL). Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding.

Amenorrhea was defined as any 28-day period during treatment (not including the ODI) without a bleeding intensity score \>1 after 2 courses of treatment. Participants were provided with a daily diary and (PBAC) to record information about the MBL. Bleeding intensity was graded on a 5-point scale where: 1=spotting to 5=heavy bleeding.

UFS-SSS is an 8 question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. Each question was answered on a 5-point scale where 1=Not at all to 5=A very great deal. The sum of the total scores was transformed to a range of 0=no symptoms (best) to 100=most severe symptoms (worst). A negative percentage change from Baseline indicates improvement.

The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative change from Baseline indicates improvement.

Safety Population included all study participants who received at least 1 dose of study treatment.

Following the baseline assessment no treatment period, telapristone acetate 12 mg, vaginally, once daily for 18 weeks (Course 1) and repeated for an additional 18 weeks (Course 2) following the ODI.

Black or African American

Native Hawaiian or Other Pacific Islander

White

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Intent-to-Treat (ITT) population included all participants who were randomized and received study drug.

ITT population included all participants who were randomized and received study drug.

Percentage change in the last value on drug Course 1.

Percentage change in the last value on drug Course 2.

Percentage Change from BL: Course 1

Percentage Change from BL: Course 2

ITT population included all participants who were randomized and received study drug. Number analyzed is the number of participants with data available at the given time-point.

Percentage Change in PBAC Scores From Baseline to the End of Treatment Courses 1 and 2

Percentage Change: Course 2, Week 24 Follow-up

Percentage Change in Transformed Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change from BL: Course 2, Week 24 Follow-up Visit

ITT population consisted of all participants who were randomized and received study drug. Number analyzed is the number of participants with data available at the given time-point.

Percentage Change in the Individual UFS-SSS Subscale Score Question 1 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 2 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 3 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 4 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 5 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 6 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 7 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in the Individual UFS-SSS Subscale Score Question 8 From Baseline to the End of Treatment Courses 1 and 2 and the Course 2 Week 24 Follow-up Visit

Percentage Change in Total Uterine Fibroid Volume From Baseline to the End of Treatment Courses 1 and 2

Telapristone acetate 12 milligrams (mg), orally, once daily for two 18-weeks courses (Treatment Courses 1 and 2) separated by an off-drug interval (ODI).

Telapristone acetate, orally, once daily for three 18-weeks courses separated by an ODI.

Telapristone acetate

To determine the safety of extended treatment with Proellex® in women who have successfully completed either study ZPV-201 \[NCT02323646\] or ZPU-203 \[NCT02301897\] and meet eligibility criteria.

This study will be for participants who had completed either ZPV-201 or ZPU-203.

An Extension Study of 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

An Open-Label Extension Study of 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. Each question was answered on a 5-point scale where 1=Not at all to 5=A very great deal. The sum of the total scores was transformed to a range of 0=no symptoms (best) to 100=most severe symptoms (worst). A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 1: During the previous 3 months how distressed were you by "heavy bleeding during your menstrual period"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 2: During the previous 3 months how distressed were you by "passing blood clots during your menstrual period"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 3: During the previous 3 months how distressed were you by "fluctuation in the duration of your menstrual period compared to your previous cycle"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 4: During the previous 3 months how distressed were you by "fluctuation in the length of your monthly cycle compared to your previous cycles"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 5: During the previous 3 months how distressed were you by "feeling tightness or pressure in your pelvic area"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 6: During the previous 3 months how distressed were you by "frequent urination during the daytime hours"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 7: During the previous 3 months how distressed were you by "frequent night time urination"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

UFS-SSS is an 8-question assessment tool used to measure symptom severity and has been validated as a three month look back questionnaire. The participant answered UFS-SSS subscale question 8: During the previous 3 months how distressed were you by "feeling fatigued"? using a 5-point scale where 1=Not at all to 5=A very great deal. A negative percentage change from Baseline indicates improvement.

Safety population consisted of all study participants who were randomized, received study drug and had some post-baseline safety data.

Telapristone acetate 12 mg, orally, once daily for two 18-weeks courses (Treatment Courses 1 and 2) separated by an off-drug interval (ODI).

Safety population included all study participants who were randomized, received study drug and had some post-baseline safety data.

Intent-to-treat (ITT) population included all participants who received study drug.

Percentage of Participants in Amenorrhea

ITT population included all participants who received study drug.

Percentage Change From Baseline in Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 1

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 2

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 3

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 4

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 5

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 6

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 7

Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 8

Change from Baseline to Week 18 Course 1

ITT population Included all participants who received study drug.

Change From Baseline in Pictorial Blood Loss Assessment Chart (PBAC) Score

ITT population Included all participants who received study drug. MRI data was only available for 3 participants.

Percentage Change From Baseline in Total Uterine Fibroid Volume

Carcinoma

Carcinoma in Situ

Carcinoma, Lobular

Breast Carcinoma In Situ

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Carcinoma, Ductal

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Patients receive telapristone acetate transdermally and placebo PO QD for 4 weeks.

Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.

Laboratory Biomarker Analysis

Questionnaire Administration

Seema Khan

This randomized trial studies transdermal or oral telapristone acetate in treating patients undergoing surgery to remove the breast (mastectomy). Telapristone acetate may help prevent breast cancer from forming in premenopausal women. Giving telapristone acetate transdermally may be safer and have fewer side effects than oral administration.

PRIMARY OBJECTIVES:

I. To demonstrate that mean levels of telapristone (telapristone acetate) in breast tissue following gel application will result in levels that are not more than 50% lower than those following oral administration.

SECONDARY OBJECTIVES:

I. To assess whether plasma concentrations of telapristone are significantly lower with transdermal than oral therapy.

II. To compare within-breast variation of breast tissue concentration in transdermal and oral groups.

III. To measure changes in cell proliferation (marker of proliferation (Ki-67 labeling index).

IV. Explore changes in gene expression in breast tissue related to telapristone therapy.

V. Assess change in serum progesterone associated with telapristone therapy. VI. Assess the safety and tolerability of oral and transdermal administration. VII. Assess symptom measurements using BESS Questionnaire

OUTLINE: Participants are randomized to 1 of 2 treatment arms.

ARM I (TRANSDERMAL TELAPRISTONE ACETATE): Patients receive telapristone acetate transdermally and placebo orally (PO) once daily (QD) for 4 weeks.

ARM II (ORAL TELAPRISTONE ACETATE): Patients receive placebo transdermally and telapristone acetate PO QD for 4 weeks.

After completion of study treatment, patients are followed up at day 60.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oral CDB-4124 vs. Placebo in Stage I-II Primary Breast Cancer	NCT01800422	Stage IA Breast... Stage IB Breast... Stage II Breast...	telapristone ac... placebo therapeutic con... laboratory biom... questionnaire a...	18 Years -	Northwestern University
A Multi-Center, Parallel Design, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 6 and 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids	NCT02301897	Uterine Fibroid...	Telapristone Ac... Placebo	18 Years - 47 Years	Repros Therapeutics Inc.
Safety and Efficacy of Telapristone Acetate (Proellex®) Administered Vaginally for the Treatment of Uterine Fibroids	NCT02323646	Uterine Fibroid...	Placebo Telapristone Ac...	18 Years - 47 Years	Repros Therapeutics Inc.
An Extension Study of 12 mg Proellex® (Telapristone Acetate) Administered Orally in the Treatment of Premenopausal Women With Confirmed Symptomatic Uterine Fibroids	NCT02811159	Uterine Fibroid...	Telapristone ac...	18 Years - 47 Years	Repros Therapeutics Inc.
Oral CDB-4124 vs. Placebo in Stage I-II Primary Breast Cancer	NCT01800422	Stage IA Breast... Stage IB Breast... Stage II Breast...	telapristone ac... placebo therapeutic con... laboratory biom... questionnaire a...	18 Years -	Northwestern University
Safety and Efficacy of Telapristone Acetate (Proellex®) Administered Vaginally for the Treatment of Uterine Fibroids	NCT02323646	Uterine Fibroid...	Placebo Telapristone Ac...	18 Years - 47 Years	Repros Therapeutics Inc.
Oral CDB-4124 vs. Placebo in Stage I-II Primary Breast Cancer	NCT01800422	Stage IA Breast... Stage IB Breast... Stage II Breast...	telapristone ac... placebo therapeutic con... laboratory biom... questionnaire a...	18 Years -	Northwestern University
Safety and Efficacy of Telapristone Acetate (Proellex®) Administered Vaginally for the Treatment of Uterine Fibroids	NCT02323646	Uterine Fibroid...	Placebo Telapristone Ac...	18 Years - 47 Years	Repros Therapeutics Inc.
Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy	NCT02314156	BRCA1 Mutation ... BRCA2 Mutation ... Ductal Breast C... Lobular Breast ... Stage 0 Breast ... Stage IA Breast... Stage IB Breast... Stage IIA Breas... Stage IIB Breas...	Telapristone Ac... Placebo Telapristone Ac... Placebo Laboratory Biom... Questionnaire A...	18 Years -	Northwestern University

Spots Global Cancer Trial Database for telapristone acetate