Safety and Efficacy of Telapristone Acetate (Proellex®) i... | NCT01728454

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 milligrams (mg)/day separated by an off-drug interval (ODI) in Stage 3.	Drug: Placebo
Telapristone acetate 6 mg	Experimental	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.	Drug: Telapristone acetate
Telapristone acetate 12 mg	Experimental	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 12 mg capsules, orally once daily for 18 weeks. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an ODI in Stage 3.	Drug: Telapristone acetate

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo matching capsules, orally, once daily for 18 weeks.	Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Individual Biberoglu Behrman Symptom Severity Scale (BBSS) Score for Dysmenorrhea	The BBSS scale defined dysmenorrhea according to the loss of work efficiency and need for bed rest. The dysmenorrhea was graded on a scale from 0 to 3 where, 0 = None; 1 = Mild (some loss in work efficiency); 2 = Moderate (in bed part of the day, occasional loss of work efficiency); 3 = Severe (in bed one or more days, incapacitation), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.	Baseline (28-day Baseline Menstrual Cycle) to the last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and at the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)
Change From Baseline in Individual BBSS Score for Dyspareunia	The BBSS scale defined deep dyspareunia according to the limitation of sexual activity. The dyspareunia was graded on a scale from 0 to 3 where, 0= None (no discomfort); 1= Mild (tolerated discomfort); 2= Moderate (intercourse painful to the point of interruption); 3= Severe (intercourse avoided because of pain), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement..	Baseline (28-day Baseline Menstrual Cycle) to the last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and at the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)
Change From Baseline in Individual BBSS Score for Non-Menstrual Pelvic Pain	The BBSS scale defined non-menstrual pelvic pain according to various degrees of discomfort and use of analgesics. The non-menstrual pelvic pain was graded on a scale from 0 to 3 where, 0= None (absence of pain); 1= Mild (occasional pelvic discomfort); 2= Moderate (noticeable discomfort for most of the cycle); 3= Severe (pain persisting during the cycle or requiring strong analgesics), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Prescription Analgesics Usage	An analgesic was any member of the group of drugs used to achieve analgesia, relief from pain. Prescription analgesics are analgesics prescribed by the physician. Participants were provided with a daily diary to record the number of pills of non-narcotic prescription and narcotic analgesics taken for endometriosis-related pain symptoms each day. Daily number of pills were standardized to a 28-day period for each interval (Baseline and On-drug Cycle 1) calculated as the sum of pills in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adult females between 18 and 47 years of age using prescription analgesics for endometriosis pain and with a Biberoglu Behrman Symptom Severity Scale (BBSS) score ≥7 at screening (assessed over the previous 28 days).
Endometriosis diagnosis must have been surgically confirmed within 7 years. A laparoscopic diagnosis is acceptable.
Participants must have a history of at least 3 regular menstrual cycles in which symptoms of endometriosis occurred immediately prior to screening.
Normal or abnormal but non-clinically significant transvaginal ultrasound.
History of menstrual events occurring in regular cycles.
Agreement not to attempt to become pregnant during the trial.
Agreement to limit alcohol consumption to no more than 2 drinks per week and to avoid alcohol consumption within 48 hours before each visit.
Ability to complete a daily electronic participant 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 for 30 days after discontinuation of study medication. 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 the Screening and Baseline visits, and subsequent study visits.
A Body Mass Index (BMI) between 18 and 39 inclusive.
Is available for all treatment and follow-up visits.

Exclusion Criteria:

Post-menopausal woman, defined as either; six (6) months or more (immediately prior to screening visit) without a menstrual period, or prior hysterectomy and/or oophorectomy.
Pregnant or lactating or is attempting or expecting to become pregnant during the 6-7 month study period.
Women with abnormally high liver enzymes or liver disease [alanine transaminase (ALT) or aspartate aminotransferase (AST) exceeding 2 x upper limit of normal (ULN) and total bilirubin exceeding 1.5 x ULN at screening and confirmed on repeat].
Received an investigational drug in the 30 days prior to the screening for this study.
History of polycystic ovary syndrome (PCOS).
Concurrent use of any testosterone, androgen, anabolic steroids, dehydroepiandrosterone (DHEA) or hormonal products for at least 2 weeks prior to screening and during the study. Oral contraceptive use for control of endometriosis symptoms is acceptable for the first 28-days of the study.
Use of Depo-Provera® in the preceding 6 months.
Use of Gonadotrophin releasing hormone (GnRH) as (e.g. Lupron Depot) within 3 months of the first dose of study drug (Lupron Depot must have a wash-out period of 3 months after the period of duration of the Lupron dose).
Has an intrauterine device (IUD) in place. Copper IUDs (non-hormone containing will be permitted).
Presence of intramural fibroids that impact the endometrial stripe, submucosal fibroids (any size), or endometrial polyps. Subserosal and intramural fibroids with no impact on the endometrial stripe are acceptable.
Presence of endometrioma(s).
Present history or condition that causes non-endometriosis related dyspareunia (e.g. vulvar vestibulitis).
Past or present history of thrombophlebitis or thromboembolic disorders.
Known or suspected carcinoma of the breast or reproductive organs.
History of abnormal electrocardiogram (ECG) that, in the opinion of the investigator, is clinically significant and will prevent the participant from completing the study, including a QTc (corrected QT interval) of greater than 450 milliseconds (ms).
Cervical dysplasia classified as Atypical Squamous Cells of Undetermined Significance (ASCUS) associated with high-risk human papilloma virus (HPV) or Low/High Grade Squamous Intraepithelial Lesion (LGSIL or HGSIL).
History of abnormal endometrial biopsy including the presence of Endometrial Intraepithelial Neoplasia (EIN).
Recent history (within past 6 months) of alcoholism or drug abuse.
Known active infection with Human Immunodeficiency Virus (HIV), Hepatitis A, B or C.
Previous history of auto-immune disease and/or positive antinuclear antigen (ANA).
Endometrial stripe ≥18 mm in thickness at Visit 1.
Women currently taking cimetidine or spironolactone.
Clinically significant abnormal findings on screening examination and laboratory assessments or any condition which in the opinion of the investigator would interfere with the participant's ability to comply with the study instructions or endanger the participant if she took part in the study.

Name	Affiliation	Role
Anna Chan	Allergan	Study Director

PubMed Identifier	Type	Citation	Retractions
31069056	Derived	Rolla E. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Res. 2019 Apr 23;8:F1000 Faculty Rev-529. doi: 10.12688/f1000research.14817.1. eCollection 2019.

Label	URL
Sponsor corporate web page	View source

ID	Title	Description
FG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 milligrams (mg)/day separated by an off-drug interval (ODI) in Stage 3.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Aug 30, 2016	May 23, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Individual Biberoglu Behrman Symptom Severity Scale (BBSS) Score for Dysmenorrhea

The BBSS scale defined dysmenorrhea according to the loss of work efficiency and need for bed rest. The dysmenorrhea was graded on a scale from 0 to 3 where, 0 = None; 1 = Mild (some loss in work efficiency); 2 = Moderate (in bed part of the day, occasional loss of work efficiency); 3 = Severe (in bed one or more days, incapacitation), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

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

Posted

Mean

Standard Deviation

score on a scale per 28-day period

Baseline (28-day Baseline Menstrual Cycle) to the last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and at the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.
OG002	Telapristone Acetate 12 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 12 mg capsules, orally once daily for 18 weeks. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an ODI in Stage 3.

Units	Counts
Participants	OG00017 OG00120 OG00223

Title

Denominators

Categories

Baseline

- ParticipantsOG00017
- ParticipantsOG00120
- ParticipantsOG00223

Title	Measurements

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	On-Drug Cycle 1	Wilcoxon Rank- Sum Test		0.0360														Superiority
OG000 OG002	On-Drug Cycle 1	Wilcoxon Rank- Sum Test

Primary

Change From Baseline in Individual BBSS Score for Dyspareunia

The BBSS scale defined deep dyspareunia according to the limitation of sexual activity. The dyspareunia was graded on a scale from 0 to 3 where, 0= None (no discomfort); 1= Mild (tolerated discomfort); 2= Moderate (intercourse painful to the point of interruption); 3= Severe (intercourse avoided because of pain), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement..

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

Posted

Mean

Standard Deviation

score on a scale per 28-day period

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg

Primary

Change From Baseline in Individual BBSS Score for Non-Menstrual Pelvic Pain

The BBSS scale defined non-menstrual pelvic pain according to various degrees of discomfort and use of analgesics. The non-menstrual pelvic pain was graded on a scale from 0 to 3 where, 0= None (absence of pain); 1= Mild (occasional pelvic discomfort); 2= Moderate (noticeable discomfort for most of the cycle); 3= Severe (pain persisting during the cycle or requiring strong analgesics), with higher scores indicating more severe symptoms. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

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

Posted

Mean

Standard Deviation

score on a scale per 28-day period

Baseline (28-day Baseline Menstrual Cycle) to the last day dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and to the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.

Secondary

Change From Baseline in Prescription Analgesics Usage

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

Posted

Mean

Standard Deviation

pills per 28-day period

Baseline (28-day Baseline Menstrual Cycle) to the last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.

Secondary

Percentage Change From Baseline in Prescription Analgesics Usage

An analgesic was any member of the group of drugs used to achieve analgesia, relief from pain. Prescription analgesics are analgesics prescribed by the physician. Participants were provided with a daily diary to record the number of pills of non-narcotic prescription and narcotic analgesics taken for endometriosis-related pain symptoms each day. Daily number of pills were standardized to a 28-day period for each interval (Baseline and last 28-days On-drug Cycle 1) calculated as the sum of pills in the interval divided by the number of the days in the interval multiplied by 28.The percent change from baseline in the analgesic usage was determined by subtracting the baseline analgesic usage from the analgesic usage during the last nominal 28 day menstrual cycle, divided by the baseline analgesic usage, and multiplied by 100%. A negative percent change from Baseline indicates improvement.

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

Posted

Mean

Standard Deviation

percent change

Baseline (28-day Baseline Menstrual Cycle) to last 28 days of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg

Secondary

Change From Baseline in Non-Prescription Analgesics Usage

An analgesic was any member of the group of drugs used to achieve analgesia, relief from pain. Nonprescription analgesics are over-the-counter (OTC) analgesics. Participants were provided with a daily diary to record the number of pills of OTC drugs taken for endometriosis-related pain symptoms each day. Daily number of pills were standardized to a 28-day period for each interval (Baseline and On-drug Cycle 1) calculated as the sum of pills in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

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

Posted

Mean

Standard Deviation

pills per 28-day period

Baseline (28-day Baseline Menstrual Cycle) to last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.

Secondary

Percentage Change From Baseline in Non-Prescription Analgesics Usage

An analgesic was any member of the group of drugs used to achieve analgesia, relief from pain. Nonprescription analgesics are OTC analgesics. Participants were provided with a daily diary to record the number of pills of over the counter drugs taken for endometriosis-related pain symptoms each day. Daily number of pills were standardized to a 28-day period for each interval (Baseline and last 28-days On-drug Cycle 1) calculated as the sum of pills in the interval divided by the number of the days in the interval multiplied by 28. The percent change from baseline in the analgesic usage was determined by subtracting the baseline analgesic usage from the analgesic usage during the last nominal 28 day menstrual cycle, divided by the baseline analgesic usage, and multiplied by 100%. A negative percent change indicates improvement.

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

Posted

Mean

Standard Deviation

percent change

Baseline (28-day Baseline Menstrual Cycle) to last 28 days of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg

Secondary

Change From Baseline in Total Analgesics Usage

An analgesic was any member of the group of drugs used to achieve analgesia, relief from pain. The total analgesics is comprised of prescription and non-prescription analgesics. Participants were provided with a daily diary to record the number of pills of OTC and prescription analgesics taken for endometriosis-related pain symptoms each day. The daily number of pills were standardized to a 28-day period for each interval (Baseline and On-drug Cycle 1) calculated as the sum of pills in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

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

Posted

Mean

Standard Deviation

pills per 28-day period

Baseline (28-day Baseline Menstrual Cycle) to last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.

Secondary

Percentage Change From Baseline in Total Analgesics Usage

An analgesic was any member of the group of drugs used to achieve analgesia, relief from pain. The total analgesics is comprised of prescription and non-prescription analgesics. Participants were provided with a daily diary to record the number of pills of OTC and prescription analgesics taken for endometriosis-related pain symptoms each day. Daily number of pills were standardized to a 28-day period for each interval (Baseline and last 28-days On-drug Cycle 1) calculated as the sum of pills in the interval divided by the number of the days in the interval multiplied by 28. The percent change from baseline in the analgesic usage was determined by subtracting the baseline analgesic usage from the analgesic usage during the last nominal 28-day menstrual cycle, divided by the baseline analgesic usage, and multiplied by 100%. A negative percent change indicates improvement.

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

Posted

Mean

Standard Deviation

percent change

Baseline (28-day Baseline Menstrual Cycle) to last 28 days of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg

Secondary

Change From Baseline in BBSS Physician-Reported Scores

BBSS Physician-Reported Scores included two scores: Pelvic Tenderness Score (PTS) and Induration Score (IS). PTS was graded on a scale from 0 to 3 where, 0= None; 1= Mild (minimal tenderness on palpation); 2= Moderate (extensive tenderness on palpation); 3= Severe (unable to palpate because of tenderness). IS was graded on a scale from 0 to 3 where, 0= None; 1= Mild (uterus freely mobile, induration on the cul-de-sac); 2= Moderate (thickened and indurated adnexa and cul-de-sac, restricted uterine mobility); 3= Severe (nodular adnexa and cul-de-sac, uterus frequently frozen), with higher scores indicating more severe symptoms. A negative change from Baseline indicates improvement. Data from On-drug cycle and Off-drug interval (ODI) were reported.

ITT population included all participants who were randomized and received study drug. Last observation carried forward (LOCF) approach was used to impute missing data in this outcome measure.

Posted

Mean

Standard Deviation

score on a scale

Baseline (Day 1) to last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and at the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001

Secondary

Change From Baseline in Participant-Reported Pain Using Visual Analog Scale (VAS) Pain Score

A 100-millimeter (mm) VAS was used to grade the severity of dysmenorrhea, and non-menstrual pelvic pain. The lowest value indicated the absence of pain and the highest value indicated pain as bad as it could be; a score of 1-50 was considered mild pain, 51-80 moderate pain and 81-100 severe pain. A negative change from Baseline indicates improvement. Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain.

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

Posted

Mean

Standard Deviation

score on a scale

Baseline (Day 1) to last day of dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and at the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.

Secondary

Change From Baseline in Participant-Reported Pain Using a Numerical Rating Scale (NRS)

NRS is a valid and reliable clinical measure to assess pain intensity. Sex Avoidance Pain (SAP) and Endometriosis Pain (EP) were assessed using NRS-11 to measure pain based on pain ratings given by participants on the scale of 0 to 10 where, 0 represents "no pain" and 10 represents "the worst pain possible". Participants were provided with a daily diary to record information about participant-reported scores for endometriosis pain each day. Daily scores were standardized to a 28-day period for each interval (Baseline, On-drug Cycle 1 and Off-drug Cycle 1) calculated as the sum of scores in the interval divided by the number of the days in the interval multiplied by 28. A negative change from Baseline indicates improvement.

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

Posted

Mean

Standard Deviation

score on a scale per 28-day period

Baseline (28-day Baseline Menstrual Cycle) to the last day dosing in Cycle 1 (On-drug Cycle 1 is 18 weeks) and to the end of Off-drug Cycle 1 (Off-drug Cycle 1 is 3 weeks following On-drug Cycle 1)

ID	Title	Description
OG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
OG001	Telapristone Acetate 6 mg

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenitis	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0021 affected23 at risk EG0030 affected6 at risk EG0040 affected5 at risk EG0050 affected11 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0022 affected23 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0021 affected23 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0012 affected20 at risk EG0020 affected23 at risk EG003
Gastroenteritis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected17 at risk EG0013 affected20 at risk EG0024 affected23 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Umbilical hernia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Hot flush	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0012 affected20 at risk EG0025 affected23 at risk EG003
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0022 affected23 at risk EG003
Conjunctivitis infective	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Cystitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Endocarditis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Folliculitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0012 affected20 at risk EG0022 affected23 at risk EG003
Vulvitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0022 affected23 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Smear cervix abnormal	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0022 affected23 at risk EG003
Muscle strain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected17 at risk EG0015 affected20 at risk EG0025 affected23 at risk EG003
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected17 at risk EG0015 affected20 at risk EG0025 affected23 at risk EG003
Migraine	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0021 affected23 at risk EG003
Depression	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0022 affected23 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Intentional self-injury	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Mood swings	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0022 affected23 at risk EG003
Asymptomatic bacteriuria	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0021 affected23 at risk EG003
Urinary tract infection	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Adnexa uteri pain	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Amenorrhoea	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Breast pain	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Breast tenderness	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0022 affected23 at risk EG003
Endometrial hypertrophy	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0019 affected20 at risk EG0022 affected23 at risk EG003
Menorrhagia	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Nipple pain	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected17 at risk EG0012 affected20 at risk EG0022 affected23 at risk EG003
Ovarian disorder	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0022 affected23 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Vaginal infection	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0021 affected23 at risk EG003
Vaginal odour	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Bronchitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0012 affected20 at risk EG0021 affected23 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0021 affected23 at risk EG003
Sinusitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0021 affected23 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Hysterectomy	Surgical and medical procedures	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Wisdom teeth removal	Surgical and medical procedures	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003
Lower gastrointestinal haemorrhage	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Rectal haemorrhage	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected17 at risk EG0011 affected20 at risk EG0020 affected23 at risk EG003
Uterine haemorrhage	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected17 at risk EG0010 affected20 at risk EG0020 affected23 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Tucson	Arizona	85712	United States

ID	Term
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases

ID	Title	Description
BG000	Placebo	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.
BG001	Telapristone Acetate 6 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.
BG002	Telapristone Acetate 12 mg	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 12 mg capsules, orally once daily for 18 weeks. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an ODI in Stage 3.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo (Stage 2)	Following the Stage 1 no treatment baseline assessment period, placebo matching capsules, orally, once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an off-drug interval (ODI) in Stage 3.	17	17	14	17
EG001	Telapristone Acetate 6 mg (Stage 2)	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 6 mg capsules, orally once daily for 18 weeks in Stage 2. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 6 mg/day separated by an ODI in Stage 3.	20	20	17	20
EG002	Telapristone Acetate 12 mg (Stage 2)	Following the Stage 1 no treatment baseline assessment period, telapristone acetate (Proellex®) 12 mg capsules, orally once daily for 18 weeks. Eligible participants had the option to receive 2 additional 16-week cycles of active treatment at 12 mg/day separated by an ODI in Stage 3.	23	23	18	23
EG003	Placebo:Telapristone Acetate 12 mg (Stage 3)	Eligible participants who received placebo in Stage 2 and opted to receive up to 2 additional 16-week cycles of telapristone acetate (Proellex®) 12 mg/day in Stage 3.	6	6	4	6
EG004	Telapristone Acetate 6 mg (Stage 3)	Eligible participants who received telapristone acetate 6 mg in Stage 2 and opted to receive up to 2 additional 16-week cycles of telapristone acetate (Proellex®) 6 mg/day in Stage 3.	5	5	5	5
EG005	Telapristone Acetate 12 mg (Stage 3)	Eligible participants who received telapristone acetate 12 mg in Stage 2 and opted to receive 2 additional 16-week cycles of telapristone acetate (Proellex®) 12 mg/day in Stage 3.	11	11	6	11