Uterine Fibroids
Conditions
Brief summary
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.
Detailed description
This study will be for participants who had completed either ZPV-201 or ZPU-203.
Interventions
Telapristone acetate, orally, once daily for three 18-weeks courses separated by an ODI.
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 47 Years
Healthy volunteers
No
Inclusion criteria
* Completed either study ZPV-201 \[NCT02323646\] or ZPU-203 \[NCT02301897\] * Agreement not to attempt to become pregnant during the trial * Agreement to use alcohol in moderation and record the daily consumption (note: elevated liver enzymes may result in discontinuation from the study) * Ability to complete a daily subject diary and study procedures in compliance with the protocol * Women of child-bearing potential must be willing to use double-barrier contraception during the study and off-drug intervals. Acceptable double-barrier methods are: male condom with spermicide; male condom with diaphragm; diaphragm containing spermicide plus additional intra-vaginal spermicide * Has a negative pregnancy test at Visit 1 * Subject is available for all treatment and follow-up visits
Exclusion criteria
* Subject had a significant decrease in bone mineral density while participating in ZPV-201 or ZPU-203 (total hip or spine measurement decreased by 5% or more) * Subject has undergone hysterectomy and/or bilateral oophorectomy since enrollment in ZPV-201 or ZPU-203 * Subject is pregnant or lactating or is attempting or expecting to become pregnant during the entire study period * Subjects with abnormally high liver enzymes or liver disease. \[alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 2 x upper limit of normal (ULN) and total bilirubin exceeding 1.5 x ULN at Visit 1 and confirmed on repeat\]. * Subject has a hemoglobin of \<7.5 grams per deciliter (g/dL) at Visit 1 * Concurrent use of any testosterone, progestin, androgen, estrogen, anabolic steroids, dehydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to Visit 1 * Use of oral contraceptives in the 30 days preceding screening. Use of Depo-Provera® in the preceding 10 months * Use of Gonadotrophin releasing hormone agonist (GnRHas) (e.g. Lupron Depot) within 3 months prior to screening (Lupron Depot must have a wash-out period of 3 months prior to screening) * Has an intra-uterine device (IUD) in place * Current cervical dysplasia classified as Atypical Squamous Cells of Undetermined Significance (ASCUS) associated with high-risk human papilloma virus (HPV) * Current diagnosis of Low/High Grade Squamous Intraepithelial Lesion (LGSIL or HGSIL), endometrial polyps or hyperplasia * Observation or history of abnormal endometrial biopsy including the presence of endometrial intraepithelial neoplasia (EIN) * Recent history (within past 6 months) of alcoholism or drug abuse * Endometrial stripe ≥18 mm in thickness at Visit 1 (subject may be enrolled with sponsor approval) * Subject is currently taking cimetidine or spironolactone or has taken them in the last 30 days * Clinically significant abnormal findings on Visit 1 examination and laboratory assessments or any condition which in the opinion of the investigator would interfere with the subject's ability to comply with the study instructions or endanger the subject if she took part in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Amenorrhea | At the end of 18 weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 1 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 2 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 3 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 4 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 5 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 6 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 7 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 8 | Baseline to the end of 18-weeks Treatment Course 1 | 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. |
| Change From Baseline in Pictorial Blood Loss Assessment Chart (PBAC) Score | Baseline to the end of 18-weeks Treatment Course 1 | 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). |
| Percentage Change From Baseline in Total Uterine Fibroid Volume | Baseline to the end of 18-weeks Treatment Course 1 | The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative percentage change from Baseline indicates improvement. |
Countries
United States
Participant flow
Pre-assignment details
Participants who had successfully completed either study ZPV-201 \[NCT02323646\] or ZPU-203 \[NCT02301897\] were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Telapristone Acetate 12 mg Telapristone acetate 12 mg, orally, once daily for two 18-weeks courses (Treatment Courses 1 and 2) separated by an off-drug interval (ODI). | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Course 1 | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Telapristone Acetate 12 mg | — |
|---|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 3.62 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 20 Participants | — |
| Sex: Female, Male Male | 0 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 11 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Change From Baseline in Pictorial Blood Loss Assessment Chart (PBAC) Score
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).
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population Included all participants who received study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Telapristone Acetate 12 mg | Change From Baseline in Pictorial Blood Loss Assessment Chart (PBAC) Score | Baseline | 139.50 score on a scale | Standard Deviation 196.111 |
| Telapristone Acetate 12 mg | Change From Baseline in Pictorial Blood Loss Assessment Chart (PBAC) Score | Change from Baseline to Week 18 Course 1 | -81.10 score on a scale | Standard Deviation 239.79 |
p-value: 0.0645Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 1
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 1 | -10.50 percent change | Standard Deviation 26.253 |
p-value: 0.25Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 2
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 2 | -5.83 percent change | Standard Deviation 18.157 |
p-value: 0.5Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 3
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 3 | -8.75 percent change | Standard Deviation 23.333 |
p-value: 0.25Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 4
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 4 | -3.75 percent change | Standard Deviation 16.771 |
p-value: 1Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 5
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 5 | -4.17 percent change | Standard Deviation 33.278 |
p-value: 0.875Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 6
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 6 | -7.33 percent change | Standard Deviation 22.675 |
p-value: 0.5Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 7
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 7 | 6.67 percent change | Standard Deviation 35.21 |
p-value: 0.5Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 8
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in the Individual UFS-SSS Subscale Score Question 8 | -6.67 percent change | Standard Deviation 16.579 |
p-value: 0.25Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score
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.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population included all participants who received study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in Total Uterine Fibroid System Quality of Life Survey System Severity (UFS-SSS) Score | -7.21 percent change | Standard Deviation 20.046 |
p-value: 0.125Wilcoxon Signed-Rank Test
Primary
Percentage Change From Baseline in Total Uterine Fibroid Volume
The total uterine fibroid volume was measured by Magnetic Resonance Imaging (MRI). A negative percentage change from Baseline indicates improvement.
Time frame: Baseline to the end of 18-weeks Treatment Course 1
Population: ITT population Included all participants who received study drug. MRI data was only available for 3 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telapristone Acetate 12 mg | Percentage Change From Baseline in Total Uterine Fibroid Volume | 0.00 percent change | Standard Deviation 0 |
Primary
Percentage of Participants in Amenorrhea
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.
Time frame: At the end of 18 weeks Treatment Course 1
Population: Intent-to-treat (ITT) population included all participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telapristone Acetate 12 mg | Percentage of Participants in Amenorrhea | 35.00 percentage of participants |
p-value: 0.1797Chi-Square Test