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Clinical Trial Results:
A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids

Summary
EudraCT number	2013-000082-37
Trial protocol	GB
Global end of trial date	08 Dec 2015

Results information
Results version number	v1(current)
This version publication date	24 Dec 2016
First version publication date	24 Dec 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

M12-813

ISRCTN number

US NCT number

NCT01817530

WHO universal trial number (UTN)

Sponsor organisation name

Abbvie Deutschland GmbH & Co.KG

Sponsor organisation address

Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4XE

Public contact

Charlotte Owens, Abbvie Deutschland GmbH & Co.KG, charlotte.owens@Abbvie.com

Scientific contact

Charlotte Owens, Abbvie Deutschland GmbH & Co.KG, charlotte.owens@Abbvie.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

08 Dec 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

08 Dec 2015

Was the trial ended prematurely?

Main objective of the trial

To assess the safety and efficacy of elagolix (ABT-620) alone and in combination with two different strengths of add-back therapy (estradiol/norethindrone acetate tablets [E2/NETA]), versus placebo to reduce heavy menstrual bleeding (HMB) (which is defined as greater than 80 mL blood loss per menstrual cycle) associated with uterine fibroids, and to reduce fibroid volume and uterine volume in premenopausal women 18 to 51 years of age.

Protection of trial subjects

Participant and/or legal guardian read and understood the information provided about the study and gave written permission.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Mar 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

Canada: 2

Country: Number of subjects enrolled

Chile: 23

Country: Number of subjects enrolled

Puerto Rico: 12

Country: Number of subjects enrolled

United States: 524

Worldwide total number of subjects

567

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

567

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Overall, 567 female subjects were enrolled into the study across 86 sites (5 sites in the UK, 4 in Chile, 2 in Canada, 4 in Puerto Rico, and 71 in the US). (Four subjects were randomized in error; they were not dosed and were excluded from all analyses including demographic summaries).

Screening details

The study included a Screening Period of approximately 2.5 to 3.5 months prior to first dose. A Washout Period of up to 6 months prior to screening, if applicable, may have also been required.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Each active elagolix dose was identical in appearance to its matched placebo; each active E2/NETA dose was identical in appearance to its matched placebo. The study site personnel and subject remained blinded to each subject's treatment throughout the course of the study.

Are arms mutually exclusive

Yes

Cohort 1: Placebo

Arm description

Placebo for elagolix and placebo for E2/NETA twice daily (BID)

Arm type

Placebo

Investigational medicinal product name

Elagolix placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 1: A morning dose of 2 tablets and an evening dose of 2 tablets were taken each day approximately 12 hours apart.

Investigational medicinal product name

E2/NETA placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 1: A morning dose of 1 capsule was taken each day.

Cohort 1: Elagolix 300 mg BID

Arm description

Elagolix 300 mg BID alone

Arm type

Experimental

Investigational medicinal product name

Elagolix

Investigational medicinal product code

ABT-620

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 1: A morning dose of 2 tablets and an evening dose of 2 tablets were taken each day approximately 12 hours apart.

Investigational medicinal product name

E2/NETA placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 1: A morning dose of 1 capsule was taken each day.

Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD

Arm description

Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)

Arm type

Experimental

Investigational medicinal product name

Elagolix

Investigational medicinal product code

ABT-620

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 1: A morning dose of 2 tablets and an evening dose of 2 tablets were taken each day approximately 12 hours apart.

Investigational medicinal product name

0.5 mg estradiol / 0.1 mg norethindrone acetate

Investigational medicinal product code

Other name

Activelle, Activella, LD E2/NETA

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 1: 1 capsule was taken each day.

Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD

Arm description

Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD

Arm type

Experimental

Investigational medicinal product name

Elagolix

Investigational medicinal product code

ABT-620

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 1: A morning dose of 2 tablets and an evening dose of 2 tablets were taken each day approximately 12 hours apart.

Investigational medicinal product name

1 mg estradiol / 0.5 mg norethindrone acetate

Investigational medicinal product code

Other name

Activelle, Activella, SD E2/NETA

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 1: A morning dose of 1 capsule was taken each day approximately 12 hours apart.

Cohort 2: Placebo

Arm description

Placebo for elagolix and E2/NETA QD

Arm type

Placebo

Investigational medicinal product name

Elagolix placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 4 tablets was taken each day.

Investigational medicinal product name

E2/NETA placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 1 capsule was taken each day.

Cohort 2: Elagolix 600 mg QD

Arm description

Elagolix 600 mg QD alone

Arm type

Experimental

Investigational medicinal product name

Elagolix

Investigational medicinal product code

ABT-620

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 4 tablets was taken each day.

Investigational medicinal product name

E2/NETA placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 1 capsule was taken each day.

Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD

Arm description

Elagolix 600 mg QD plus LD E2/NETA QD

Arm type

Experimental

Investigational medicinal product name

Elagolix

Investigational medicinal product code

ABT-620

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 4 tablets was taken each day.

Investigational medicinal product name

0.5 mg estradiol / 0.1 mg norethindrone acetate

Investigational medicinal product code

Other name

Activelle, Activella, LD E2/NETA

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 1 capsule was taken each day.

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD

Arm description

Elagolix 600 mg QD plus SD E2/NETA QD

Arm type

Experimental

Investigational medicinal product name

Elagolix

Investigational medicinal product code

ABT-620

Other name

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 4 tablets was taken each day.

Investigational medicinal product name

1 mg estradiol / 0.5 mg norethindrone acetate

Investigational medicinal product code

Other name

Activelle, Activella, SD E2/NETA

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Cohort 2: A morning dose of 1 capsule was taken each day.

Number of subjects in period 1	Cohort 1: Placebo	Cohort 1: Elagolix 300 mg BID	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD	Cohort 2: Placebo	Cohort 2: Elagolix 600 mg QD	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD
Started	65	65	64	65	78	77	76	77
Completed	50	52	53	52	67	58	53	53
Not completed	15	13	11	13	11	19	23	24
Consent withdrawn by subject	3	4	7	3	5	3	3	10
Surgery or invasive intervention	1	-	-	-	1	1	1	-
Not specified	-	1	-	-	1	-	5	-
Pregnancy	-	-	-	-	-	1	-	-
Adverse event	6	3	2	5	-	10	5	8
Lost to follow-up	1	4	2	1	3	2	8	4
Subject noncompliant	3	1	-	4	-	1	1	1
Exclusionary medication received	-	-	-	-	1	-	-	-
Lack of efficacy	1	-	-	-	-	1	-	1

Baseline characteristics

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Reporting group title

Cohort 1: Placebo

Reporting group description

Placebo for elagolix and placebo for E2/NETA twice daily (BID)

Reporting group title

Cohort 1: Elagolix 300 mg BID

Reporting group description

Elagolix 300 mg BID alone

Reporting group title

Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD

Reporting group description

Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)

Reporting group title

Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD

Reporting group description

Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD

Reporting group title

Cohort 2: Placebo

Reporting group description

Placebo for elagolix and E2/NETA QD

Reporting group title

Cohort 2: Elagolix 600 mg QD

Reporting group description

Elagolix 600 mg QD alone

Reporting group title

Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD

Reporting group description

Elagolix 600 mg QD plus LD E2/NETA QD

Reporting group title

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD

Reporting group description

Elagolix 600 mg QD plus SD E2/NETA QD

Reporting group values	Cohort 1: Placebo	Cohort 1: Elagolix 300 mg BID	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD	Cohort 2: Placebo	Cohort 2: Elagolix 600 mg QD	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD	Total
Number of subjects	65	65	64	65	78	77	76	77	567
Age categorical
Units: Subjects
Adults (18-64 years)	65	65	64	65	78	77	76	77	567
Age continuous
Units: years
arithmetic mean (standard deviation)	42.5 ± 6.14	42 ± 4.76	43 ± 5.02	43.8 ± 4.66	42.3 ± 4.78	42.1 ± 4.93	41.1 ± 5.74	42.2 ± 5.4	-
Gender categorical
Units: Subjects
Female	65	65	64	65	78	77	76	77	567
Male	0	0	0	0	0	0	0	0	0

End points

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Reporting group title

Cohort 1: Placebo

Reporting group description

Placebo for elagolix and placebo for E2/NETA twice daily (BID)

Reporting group title

Cohort 1: Elagolix 300 mg BID

Reporting group description

Elagolix 300 mg BID alone

Reporting group title

Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD

Reporting group description

Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)

Reporting group title

Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD

Reporting group description

Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD

Reporting group title

Cohort 2: Placebo

Reporting group description

Placebo for elagolix and E2/NETA QD

Reporting group title

Cohort 2: Elagolix 600 mg QD

Reporting group description

Elagolix 600 mg QD alone

Reporting group title

Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD

Reporting group description

Elagolix 600 mg QD plus LD E2/NETA QD

Reporting group title

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD

Reporting group description

Elagolix 600 mg QD plus SD E2/NETA QD

Subject analysis set title

Cohort 1: Placebo, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (placebo) in this study.

Subject analysis set title

Cohort 1: Elagolix 300 mg BID, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (elagolix 300 mg BID) in this study.

Subject analysis set title

Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (elagolix 300 mg BID plus LD E2/NETA QD) in this study.

Subject analysis set title

Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (elagolix 300 mg BID plus SD E2/NETA QD) in this study.

Subject analysis set title

Cohort 2: Placebo, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (placebo) in this study.

Subject analysis set title

Cohort 2: Elagolix 600 mg QD, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (elagolix 600 mg QD) in this study.

Subject analysis set title

Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (elagolix 600 mg QD plus LD E2/NETA QD) in this study.

Subject analysis set title

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Randomized subjects who received at least 1 dose of randomized, double-blind study drug (elagolix 600 mg QD plus SD E2/NETA QD) in this study.

Primary: Percentage of Participants With a MBL Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

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End point title

Percentage of Participants With a MBL Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

End point description

The percentage of subjects meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of < 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.

End point type

Primary

End point timeframe

Baseline, Final Month (last 28 days of treatment)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	64 ^[1]	62 ^[2]	61 ^[3]	62 ^[4]	76 ^[5]	71 ^[6]	73 ^[7]	76 ^[8]
Units: percentage of subjects
number (not applicable)	26.56	91.94	85.25	79.03	31.58	90.14	72.6	81.58

Notes
[1] - excludes subjects with < 28 days of treatment
[2] - excludes subjects with < 28 days of treatment
[3] - excludes subjects with < 28 days of treatment
[4] - excludes subjects with < 28 days of treatment
[5] - excludes subjects with < 28 days of treatment
[6] - excludes subjects with < 28 days of treatment
[7] - excludes subjects with < 28 days of treatment
[8] - excludes subjects with < 28 days of treatment

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[9]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

32.51

Confidence interval

level

95%

sides

2-sided

lower limit

11.12

upper limit

95.05

Notes
[9] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[10]

Method

Chi-squared

Confidence interval

Notes
[10] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[11]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

16.66

Confidence interval

level

95%

sides

2-sided

lower limit

6.72

upper limit

41.3

Notes
[11] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[12]

Method

Chi-squared

Confidence interval

Notes
[12] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 5

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[13]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

11.13

Confidence interval

level

95%

sides

2-sided

lower limit

4.79

upper limit

25.84

Notes
[13] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[14]

Method

Chi-squared

Confidence interval

Notes
[14] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 7

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

19.62

Confidence interval

level

95%

sides

2-sided

lower limit

7.81

upper limit

49.27

Notes
[15] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 8

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

Chi-squared

Confidence interval

Notes
[16] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 9

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[17]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

6.02

Confidence interval

level

95%

sides

2-sided

lower limit

2.95

upper limit

12.3

Notes
[17] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 10

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[18]

Method

Chi-squared

Confidence interval

Notes
[18] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 11

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[19]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

10.34

Confidence interval

level

95%

sides

2-sided

lower limit

4.79

upper limit

22.34

Notes
[19] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 12

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[20]

Method

Chi-squared

Confidence interval

Notes
[20] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Secondary: Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 days of Treatment

Top of page

End point title

Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 days of Treatment

End point description

The percentage of subjects meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.

End point type

Secondary

End point timeframe

Baseline, second last 28 days of treatment (last 56 to 29 days of treatment)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	62 ^[21]	58 ^[22]	59 ^[23]	60 ^[24]	76 ^[25]	68 ^[26]	64 ^[27]	70 ^[28]
Units: percentage of subjects
number (not applicable)	11.29	94.83	88.14	85	18.42	85.29	67.19	77.14

Notes
[21] - excludes subjects with < 56 days of treatment
[22] - excludes subjects with < 56 days of treatment
[23] - excludes subjects with < 56 days of treatment
[24] - excludes subjects with < 56 days of treatment
[25] - excludes subjects with < 56 days of treatment
[26] - excludes subjects with < 56 days of treatment
[27] - excludes subjects with < 56 days of treatment
[28] - excludes subjects with < 56 days of treatment

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[29]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

156.17

Confidence interval

level

95%

sides

2-sided

lower limit

38.04

upper limit

641.22

Notes
[29] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[30]

Method

Chi-squared

Confidence interval

Notes
[30] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[31]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

66.07

Confidence interval

level

95%

sides

2-sided

lower limit

21.1

upper limit

206.88

Notes
[31] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[32]

Method

Chi-squared

Confidence interval

Notes
[32] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 5

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[33]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

52.15

Confidence interval

level

95%

sides

2-sided

lower limit

17.42

upper limit

156.09

Notes
[33] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

122

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[34]

Method

Chi-squared

Confidence interval

Notes
[34] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 7

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[35]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

25.45

Confidence interval

level

95%

sides

2-sided

lower limit

10.45

upper limit

61.96

Notes
[35] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 8

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[36]

Method

Chi-squared

Confidence interval

Notes
[36] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 9

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[37]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

9.65

Confidence interval

level

95%

sides

2-sided

lower limit

4.38

upper limit

21.25

Notes
[37] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 10

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[38]

Method

Chi-squared

Confidence interval

Notes
[38] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 11

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

146

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[39]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

16.17

Confidence interval

level

95%

sides

2-sided

lower limit

7.13

upper limit

36.67

Notes
[39] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 12

Comparison groups

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT v Cohort 2: Placebo, mITT

Number of subjects included in analysis

146

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[40]

Method

Chi-squared

Confidence interval

Notes
[40] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Secondary: Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 days of Treatment

Top of page

End point title

Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 days of Treatment

End point description

The percentage of subjects meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.

End point type

Secondary

End point timeframe

Baseline, third last 28 days of treatment (last 84 to 57 days of treatment)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	61 ^[41]	56 ^[42]	57 ^[43]	58 ^[44]	74 ^[45]	66 ^[46]	62 ^[47]	65 ^[48]
Units: percentage of subjects
number (not applicable)	19.67	96.43	89.47	79.31	21.62	86.36	74.19	72.31

Notes
[41] - excludes subjects with < 84 days of treatment
[42] - excludes subjects with < 84 days of treatment
[43] - excludes subjects with < 84 days of treatment
[44] - excludes subjects with < 84 days of treatment
[45] - excludes subjects with < 84 days of treatment
[46] - excludes subjects with < 84 days of treatment
[47] - excludes subjects with < 84 days of treatment
[48] - excludes subjects with < 84 days of treatment

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[49]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

123.14

Confidence interval

level

95%

sides

2-sided

lower limit

25.93

upper limit

584.85

Notes
[49] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

117

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[50]

Method

Chi-squared

Confidence interval

Notes
[50] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[51]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

40.56

Confidence interval

level

95%

sides

2-sided

lower limit

13.59

upper limit

121.03

Notes
[51] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[52]

Method

Chi-squared

Confidence interval

Notes
[52] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 5

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[53]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

19.01

Confidence interval

level

95%

sides

2-sided

lower limit

7.44

upper limit

48.58

Notes
[53] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[54]

Method

Chi-squared

Confidence interval

Notes
[54] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 7

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[55]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

22.77

Confidence interval

level

95%

sides

2-sided

lower limit

9.29

upper limit

55.77

Notes
[55] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 8

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

140

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[56]

Method

Chi-squared

Confidence interval

Notes
[56] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 9

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[57]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

10.89

Confidence interval

level

95%

sides

2-sided

lower limit

4.88

upper limit

24.27

Notes
[57] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 10

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[58]

Method

Chi-squared

Confidence interval

Notes
[58] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 11

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[59]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

9.72

Confidence interval

level

95%

sides

2-sided

lower limit

4.46

upper limit

21.22

Notes
[59] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline as a covariate.

Statistical Analysis 12

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

139

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[60]

Method

Chi-squared

Confidence interval

Notes
[60] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Secondary: Percentage of Subjects Who Achieved an MBL Volume of < 80 mL at the Final Month

Top of page

End point title

Percentage of Subjects Who Achieved an MBL Volume of < 80 mL at the Final Month

End point description

Percentage of participants who achieved an MBL volume of < 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.

End point type

Secondary

End point timeframe

Final Month (last 28 days of treatment)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	64 ^[61]	62 ^[62]	61 ^[63]	62 ^[64]	76 ^[65]	71 ^[66]	73 ^[67]	76 ^[68]
Units: percentage of subjects
number (not applicable)	32.81	91.94	88.52	79.03	36.84	91.55	72.6	85.53

Notes
[61] - excludes subjects with < 28 days of treatment
[62] - excludes subjects with < 28 days of treatment
[63] - excludes subjects with < 28 days of treatment
[64] - excludes subjects with < 28 days of treatment
[65] - excludes subjects with < 28 days of treatment
[66] - excludes subjects with < 28 days of treatment
[67] - excludes subjects with < 28 days of treatment
[68] - excludes subjects with < 28 days of treatment

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[69]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

24.73

Confidence interval

level

95%

sides

2-sided

lower limit

8.57

upper limit

71.32

Notes
[69] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[70]

Method

Chi-squared

Confidence interval

Notes
[70] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[71]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

17.21

Confidence interval

level

95%

sides

2-sided

lower limit

6.57

upper limit

45.05

Notes
[71] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[72]

Method

Chi-squared

Confidence interval

Notes
[72] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 5

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[73]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

8.69

Confidence interval

level

95%

sides

2-sided

lower limit

3.79

upper limit

19.92

Notes
[73] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[74]

Method

Chi-squared

Confidence interval

Notes
[74] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 7

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[75]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

18.67

Confidence interval

level

95%

sides

2-sided

lower limit

7.11

upper limit

49.02

Notes
[75] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 8

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[76]

Method

Chi-squared

Confidence interval

Notes
[76] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 9

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[77]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.94

Confidence interval

level

95%

sides

2-sided

lower limit

2.43

upper limit

10.04

Notes
[77] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 10

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[78]

Method

Chi-squared

Confidence interval

Notes
[78] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 11

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[79]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

11.76

Confidence interval

level

95%

sides

2-sided

lower limit

5.17

upper limit

26.79

Notes
[79] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 12

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[80]

Method

Chi-squared

Confidence interval

Notes
[80] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Secondary: Percentage of Subjects With a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

Top of page

End point title

Percentage of Subjects With a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

End point description

Percentage of participants with a >= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.

End point type

Secondary

End point timeframe

Baseline, Final Month (last 28 days of treatment)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	64 ^[81]	62 ^[82]	61 ^[83]	62 ^[84]	76 ^[85]	71 ^[86]	73 ^[87]	76 ^[88]
Units: percentage of subjects
number (not applicable)	31.25	93.55	86.89	82.26	35.53	90.14	79.45	85.53

Notes
[81] - excludes subjects with < 28 days of treatment
[82] - excludes subjects with < 28 days of treatment
[83] - excludes subjects with < 28 days of treatment
[84] - excludes subjects with < 28 days of treatment
[85] - excludes subjects with < 28 days of treatment
[86] - excludes subjects with < 28 days of treatment
[87] - excludes subjects with < 28 days of treatment
[88] - excludes subjects with < 28 days of treatment

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[89]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

31.48

Confidence interval

level

95%

sides

2-sided

lower limit

10.02

upper limit

98.83

Notes
[89] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[90]

Method

Chi-squared

Confidence interval

Notes
[90] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[91]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

14.39

Confidence interval

level

95%

sides

2-sided

lower limit

5.77

upper limit

35.91

Notes
[91] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[92]

Method

Chi-squared

Confidence interval

Notes
[92] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 5

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[93]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

9.82

Confidence interval

level

95%

sides

2-sided

lower limit

4.23

upper limit

22.8

Notes
[93] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

126

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[94]

Method

Chi-squared

Confidence interval

Notes
[94] - b. P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 7

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[95]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

16.58

Confidence interval

level

95%

sides

2-sided

lower limit

6.66

upper limit

41.26

Notes
[95] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 8

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[96]

Method

Chi-squared

Confidence interval

Notes
[96] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 9

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[97]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.02

Confidence interval

level

95%

sides

2-sided

lower limit

3.36

upper limit

14.68

Notes
[97] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 10

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

149

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[98]

Method

Chi-squared

Confidence interval

Notes
[98] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Statistical Analysis 11

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[99]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

10.73

Confidence interval

level

95%

sides

2-sided

lower limit

4.85

upper limit

23.76

Notes
[99] - P value for test of difference between each elagolix dose group and placebo is from a logistic regression model including treatment as the main effect and baseline value as a covariate.

Statistical Analysis 12

Comparison groups

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT v Cohort 2: Placebo, mITT

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[100]

Method

Chi-squared

Confidence interval

Notes
[100] - P value for test of difference between each elagolix dose group and placebo is from a chi-square test.

Secondary: Percentage of Subjects Who Achieved Amenorrhea During the Last 56 Days of Treatment

Top of page

End point title

Percentage of Subjects Who Achieved Amenorrhea During the Last 56 Days of Treatment

End point description

Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and non-validated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment.

End point type

Secondary

End point timeframe

Last 56 days of treatment (after 10 days from first dose date)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	61 ^[101]	57 ^[102]	57 ^[103]	60 ^[104]	75 ^[105]	67 ^[106]	63 ^[107]	66 ^[108]
Units: percentage of participants
number (not applicable)	1.6	56.1	33.3	28.3	1.3	50.7	17.5	22.7

Notes
[101] - excludes subjects with less than 66 days of treatment
[102] - excludes subjects with less than 66 days of treatment
[103] - excludes subjects with less than 66 days of treatment
[104] - excludes subjects with less than 66 days of treatment
[105] - excludes subjects with less than 66 days of treatment
[106] - excludes subjects with less than 66 days of treatment
[107] - excludes subjects with less than 66 days of treatment
[108] - excludes subjects with less than 66 days of treatment

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 4

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 5

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 6

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Secondary: Percentage of Subjects Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment

Top of page

End point title

Percentage of Subjects Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment

End point description

Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and non-validated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment.

End point type

Secondary

End point timeframe

Last 56 days of treatment (after 10 days from first dose date)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	61 ^[109]	57 ^[110]	57 ^[111]	60 ^[112]	75 ^[113]	67 ^[114]	63 ^[115]	66 ^[116]
Units: percentage of subjects
number (not applicable)	1.6	75.4	52.6	43.3	2.7	67.2	31.7	34.8

Notes
[109] - excludes subjects with < 66 days of treatment
[110] - excludes subjects with < 66 days of treatment
[111] - excludes subjects with < 66 days of treatment
[112] - excludes subjects with < 66 days of treatment
[113] - excludes subjects with < 66 days of treatment
[114] - excludes subjects with < 66 days of treatment
[115] - excludes subjects with < 66 days of treatment
[116] - excludes subjects with < 66 days of treatment

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

118

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

121

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 4

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

142

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 5

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

138

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Statistical Analysis 6

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

141

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Fisher exact

Confidence interval

Secondary: Mean Change in the Number of Bleeding Days from Baseline to Month 6

Top of page

End point title

Mean Change in the Number of Bleeding Days from Baseline to Month 6

End point description

The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.

End point type

Secondary

End point timeframe

Baseline, Month 6

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	37 ^[117]	11 ^[118]	26 ^[119]	30 ^[120]	47 ^[121]	15 ^[122]	26 ^[123]	28 ^[124]
Units: percentage of subjects
least squares mean (standard error)	-1.2 ± 0.63	-4.9 ± 1.15	-2.7 ± 0.75	-1.1 ± 0.69	-1.4 ± 0.49	-3.3 ± 0.87	-1.3 ± 0.66	-1.8 ± 0.64

Notes
[117] - subjects with an assessment at baseline and Month 6
[118] - subjects with an assessment at baseline and Month 6
[119] - subjects with an assessment at baseline and Month 6
[120] - subjects with an assessment at baseline and Month 6
[121] - subjects with an assessment at baseline and Month 6
[122] - subjects with an assessment at baseline and Month 6
[123] - subjects with an assessment at baseline and Month 6
[124] - subjects with an assessment at baseline and Month 6

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007 ^[125]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.28

upper limit

-1.03

Variability estimate

Standard error of the mean

Dispersion value

1.32

Notes
[125] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.132 ^[126]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

0.46

Variability estimate

Standard error of the mean

Dispersion value

0.98

Notes
[126] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.876 ^[127]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.71

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.94

Notes
[127] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.055 ^[128]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.92

upper limit

0.04

Variability estimate

Standard error of the mean

Dispersion value

Notes
[128] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 5

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.898 ^[129]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.52

upper limit

1.74

Variability estimate

Standard error of the mean

Dispersion value

0.82

Notes
[129] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.59 ^[130]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.05

upper limit

1.17

Variability estimate

Standard error of the mean

Dispersion value

0.81

Notes
[130] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Secondary: Mean Change in the Number of Heavy Bleeding Days from Baseline to Month 6

Top of page

End point title

Mean Change in the Number of Heavy Bleeding Days from Baseline to Month 6

End point description

The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.

End point type

Secondary

End point timeframe

Baseline, Month 6

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	37 ^[131]	11 ^[132]	26 ^[133]	30 ^[134]	47 ^[135]	15 ^[136]	26 ^[137]	28 ^[138]
Units: percentage of subjects
least squares mean (standard error)	-1 ± 0.15	-2 ± 0.27	-1.9 ± 0.18	-1.7 ± 0.16	-0.7 ± 0.14	-1.2 ± 0.25	-1.4 ± 0.19	-1.8 ± 0.18

Notes
[131] - subjects with an assessment at baseline and Month 6
[132] - subjects with an assessment at baseline and Month 6
[133] - subjects with an assessment at baseline and Month 6
[134] - subjects with an assessment at baseline and Month 6
[135] - subjects with an assessment at baseline and Month 6
[136] - subjects with an assessment at baseline and Month 6
[137] - subjects with an assessment at baseline and Month 6
[138] - subjects with an assessment at baseline and Month 6

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[139]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.64

upper limit

-0.42

Variability estimate

Standard error of the mean

Dispersion value

0.31

Notes
[139] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[140]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.42

upper limit

-0.48

Variability estimate

Standard error of the mean

Dispersion value

0.23

Notes
[140] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[141]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

-0.25

Variability estimate

Standard error of the mean

Dispersion value

0.22

Notes
[141] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.118 ^[142]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.04

upper limit

0.12

Variability estimate

Standard error of the mean

Dispersion value

0.29

Notes
[142] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 5

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[143]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.16

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.24

Notes
[143] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[144]

Method

ANCOVA

Parameter type

difference in LS mean change

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.51

upper limit

-0.59

Variability estimate

Standard error of the mean

Dispersion value

0.23

Notes
[144] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Secondary: Change in Bleeding Severity Scores From Baseline at the Final Month

Top of page

End point title

Change in Bleeding Severity Scores From Baseline at the Final Month

End point description

The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug.

End point type

Secondary

End point timeframe

Baseline, Final Month ( last 28 days of treatment)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	51 ^[145]	19 ^[146]	33 ^[147]	37 ^[148]	61 ^[149]	24 ^[150]	48 ^[151]	42 ^[152]
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.08	-0.7 ± 0.14	-0.4 ± 0.1	-0.1 ± 0.1	-0.2 ± 0.08	-0.4 ± 0.14	-0.3 ± 0.1	-0.1 ± 0.1

Notes
[145] - subjects with an assessment at baseline and final month
[146] - subjects with an assessment at baseline and final month
[147] - subjects with an assessment at baseline and final month
[148] - subjects with an assessment at baseline and final month
[149] - subjects with an assessment at baseline and final month
[150] - subjects with an assessment at baseline and final month
[151] - subjects with an assessment at baseline and final month
[152] - subjects with an assessment at baseline and final month

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[153]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.79

upper limit

-0.15

Variability estimate

Standard error of the mean

Dispersion value

0.16

Notes
[153] - P-value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.314 ^[154]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.13

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[154] - P-value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.307 ^[155]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.39

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[155] - P-value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.106 ^[156]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

0.06

Variability estimate

Standard error of the mean

Dispersion value

0.16

Notes
[156] - P-value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.

Statistical Analysis 5

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

109

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.424 ^[157]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.15

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[157] - P-value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.528 ^[158]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.35

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[158] - P-value for test of difference between each elagolix dose group and placebo at each post-baseline time point is from an ANCOVA model with treatment as the main effect and baseline as a covariate.

Secondary: Change from Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire

Top of page

End point title

Change from Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire

End point description

The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug.

End point type

Secondary

End point timeframe

Baseline, Days 1-28, Days 29-58, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	65 ^[159]	65 ^[160]	64 ^[161]	65 ^[162]	78 ^[163]	77 ^[164]	76 ^[165]	77 ^[166]
Units: units on a scale
arithmetic mean (standard deviation)
Days 1-28; n=37, 36, 36, 34, 71, 74, 71, 67	-3.3 ± 10.11	-3.4 ± 8.21	-3.1 ± 7.88	-1.4 ± 6.42	0.4 ± 4.71	-2.7 ± 7.27	-2.1 ± 4.44	0 ± 6.26
Days 29-56; n=35, 34, 34, 28, 68, 65, 63, 63	-4.5 ± 13.12	-5.8 ± 8.78	-4.4 ± 6.59	-2.9 ± 9.44	-0.3 ± 7.13	-4.2 ± 7.72	-2.2 ± 5.54	-2.3 ± 9.31
Days 57-84; n=34, 31, 34, 28, 61, 63, 56, 54	-5.6 ± 10.94	-7.2 ± 11.04	-4.1 ± 8.4	-3.2 ± 11.26	0.1 ± 7.34	-4.5 ± 8.55	-2.2 ± 6.22	-3.8 ± 8.92
Days 85-112; n=31, 31, 31, 28, 55, 62, 55, 53	-7 ± 10.74	-7.8 ± 11.75	-5.2 ± 9.05	-3.7 ± 10.76	-0.2 ± 7.47	-5.1 ± 9.4	-3.6 ± 7.35	-4.1 ± 8.96
Days 113-140; n=28, 29, 32, 28, 56, 57, 48, 47	-4.1 ± 13.16	-7.6 ± 12.03	-5.3 ± 9.43	-3.4 ± 12.1	0.1 ± 11.92	-5.5 ± 8.44	-4 ± 8.13	-5.3 ± 8.99
Days 141-168; n=26, 29, 30, 27, 53, 51, 47, 45	-6.8 ± 14.28	-8 ± 12.65	-5.1 ± 9.94	-3.3 ± 13.01	-0.4 ± 10.46	-5.9 ± 9.45	-4.4 ± 8.21	-4.8 ± 9.3
Final Month; n=37, 34, 33, 31, 66, 70, 65, 61	-5.3 ± 13.19	-6.7 ± 11.94	-4.1 ± 10.15	-3.5 ± 12.59	-0.8 ± 11.34	-4 ± 9.4	-3.3 ± 8.09	-2.3 ± 10.56
PT Days 1-28; n=29, 30, 28, 27, 61, 63, 59, 57	-5.6 ± 13.39	-5.2 ± 12.13	-3.8 ± 10.37	-3 ± 10.69	-0.8 ± 12.46	-3.8 ± 10.53	-2 ± 8.23	-2.3 ± 7.82
PT Days29-56; n=28, 29, 30, 26, 59, 58, 53, 53	-5.7 ± 15.83	-4.1 ± 13.1	-1 ± 11.57	0 ± 9.89	-0.2 ± 12.49	-2.8 ± 11.85	-2.7 ± 7.58	-2.5 ± 8.54
PT Days 57-84; n=26, 27, 27, 24, 58, 55, 49, 47	-5.4 ± 17.08	-4 ± 14.11	-2.1 ± 10.91	-1.1 ± 10.5	-0.5 ± 13.08	-2 ± 9.79	-1.6 ± 8.35	-3.9 ± 6.87
PT Days 85-112; n=12, 10, 10, 11, 23, 26, 23, 19	-4.4 ± 17.82	-6.4 ± 12.99	-4.8 ± 10.33	0.7 ± 6.59	-2.7 ± 7.15	-2.4 ± 14.37	-3 ± 7.48	-5 ± 5.12
PT Days 113-140; n=4, 2, 1, 3, 4, 4, 4, 3	3.4 ± 27.8	-3.1 ± 2.15	1.3 ± 99999	1.4 ± 1.75	-6.2 ± 1.51	-17.3 ± 26.2	-5.6 ± 6.45	-7 ± 7.12
PT Days 141-168; n=3, 2, 1, 1, 1, 1, 4, 3	7.5 ± 27.75	-8 ± 1.42	4.1 ± 99999	-3.3 ± 99999	-10.5 ± 99999	-3.1 ± 99999	-3.3 ± 6.42	-6.4 ± 5.94

Attachments

Untitled (Filename: Table 14.2_12.2.1 stat analysis Cohort 1.pdf)
Untitled (Filename: Table 14.2_12.2.1 stat analysis Cohort 2.pdf)

Notes
[159] - n = subjects with an assessment at baseline and given time point
[160] - n = subjects with an assessment at baseline and given time point
[161] - n = subjects with an assessment at baseline and given time point; 99999 = not applicable (n=1)
[162] - n = subjects with an assessment at baseline and given time point; 99999 = not applicable (n=1)
[163] - n = subjects with an assessment at baseline and given time point; 99999 = not applicable (n=1)
[164] - n = subjects with an assessment at baseline and given time point; 99999 = not applicable (n=1)
[165] - n = subjects with an assessment at baseline and given time point
[166] - n = subjects with an assessment at baseline and given time point

No statistical analyses for this end point

Secondary: Mean Percentage Change from Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Top of page

End point title

Mean Percentage Change from Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

End point description

Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound.

End point type

Secondary

End point timeframe

Baseline, Month 3, Month 6, and Final Visit

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	65 ^[167]	65 ^[168]	64 ^[169]	65 ^[170]	78 ^[171]	77 ^[172]	76 ^[173]	77 ^[174]
Units: percentage change
arithmetic mean (standard deviation)
Month 3; n=53, 49, 52, 47, 64, 57, 53, 58	6.9 ± 35.31	-35.5 ± 26.32	-20.3 ± 33.54	-3.7 ± 39.13	6.7 ± 27.66	-33.6 ± 23.74	-17.2 ± 27.39	-1.9 ± 39.22
Month 6; n=45, 44, 48, 42, 55, 50, 44, 46	13.2 ± 48.65	-36.1 ± 30.59	-19.6 ± 32.1	0 ± 47.07	1.4 ± 30.03	-33.5 ± 31.89	-12.2 ± 40.59	-0.7 ± 42.98
Final Visit; n=53, 53, 54, 51, 66, 59, 55, 60	9 ± 46.63	-35.6 ± 30.81	-20 ± 31.73	-2.7 ± 46.63	3 ± 28.7	-34.8 ± 30.36	-12.8 ± 39.65	0 ± 40.17

Attachments

Untitled (Filename: Table 30_statistical analyses.docx)

Notes
[167] - n=subjects with an assessment at baseline and given time point
[168] - n=subjects with an assessment at baseline and given time point
[169] - n=subjects with an assessment at baseline and given time point
[170] - n=subjects with an assessment at baseline and given time point
[171] - n=subjects with an assessment at baseline and given time point
[172] - n=subjects with an assessment at baseline and given time point
[173] - n=subjects with an assessment at baseline and given time point
[174] - n=subjects with an assessment at baseline and given time point

No statistical analyses for this end point

Secondary: Mean Percentage Change from Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Top of page

End point title

Mean Percentage Change from Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

End point description

Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound.

End point type

Secondary

End point timeframe

Baseline, Month 3, Month 6, and Final Visit

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	65 ^[175]	65 ^[176]	64 ^[177]	65 ^[178]	78 ^[179]	77 ^[180]	76 ^[181]	77 ^[182]
Units: percentage change
arithmetic mean (standard deviation)
Month 3; n=53, 49, 52, 47, 64, 57, 53, 58	1.7 ± 33.61	-41.9 ± 24.87	-24.6 ± 27.58	-9.8 ± 40.31	5.4 ± 27.18	-34.4 ± 25.56	-17.5 ± 27.76	-4.6 ± 39.97
Month 6; n=45, 44, 48, 42, 55, 50, 44, 46	8.3 ± 50.97	-40.2 ± 27.6	-23.3 ± 30.34	-8.8 ± 47.81	-1.8 ± 30.1	-34.2 ± 31.14	-17.8 ± 30.49	-1.1 ± 46.66
Final Visit; n=53, 53, 54, 51, 66, 59, 55, 60	4.6 ± 48.59	-39.6 ± 28.66	-24 ± 29.93	-12.9 ± 46.2	0.1 ± 28.82	-36.4 ± 30.07	-16.6 ± 32.65	-1.6 ± 42.75

Attachments

Untitled (Filename: Table 31_statistical analyses.docx)

Notes
[175] - n=subjects with an assessment at baseline and given time point
[176] - n=subjects with an assessment at baseline and given time point
[177] - n=subjects with an assessment at baseline and given time point
[178] - n=subjects with an assessment at baseline and given time point
[179] - n=subjects with an assessment at baseline and given time point
[180] - n=subjects with an assessment at baseline and given time point
[181] - n=subjects with an assessment at baseline and given time point
[182] - n=subjects with an assessment at baseline and given time point

No statistical analyses for this end point

Secondary: Mean Percentage Change from Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Top of page

End point title

Mean Percentage Change from Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

End point description

Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound.

End point type

Secondary

End point timeframe

Baseline, Month 3, Month 6, and Final Visit

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	65 ^[183]	65 ^[184]	64 ^[185]	65 ^[186]	78 ^[187]	77 ^[188]	76 ^[189]	77 ^[190]
Units: percentage change
arithmetic mean (standard deviation)
Month 3; n=58, 52, 56, 54, 72, 63, 57, 63	7.3 ± 25.12	-30.9 ± 28.87	-19.4 ± 22.48	-7.3 ± 20.7	8.4 ± 24.26	-24.7 ± 21.98	-15.7 ± 21.84	-6.1 ± 18.81
Month 6; n=51, 47, 50, 47, 61, 56, 49, 50	17.5 ± 40.25	-35.6 ± 25.74	-21.9 ± 27.64	-13.2 ± 23.86	10.7 ± 20.73	-26 ± 29.51	-13.5 ± 25.09	-9 ± 22.12
Final Visit; n=58, 56, 56, 56, 72, 65, 58, 64	15.9 ± 38.06	-31.5 ± 31.44	-22 ± 28.52	-11.8 ± 22.56	11.6 ± 25.38	-26.6 ± 28.26	-11.5 ± 25.33	-6.7 ± 21.8

Attachments

Untitled (Filename: Table 34_statistical analyses.docx)

Notes
[183] - n=subjects who had an assessment at baseline and given time point
[184] - n=subjects who had an assessment at baseline and given time point
[185] - n=subjects who had an assessment at baseline and given time point
[186] - n=subjects who had an assessment at baseline and given time point
[187] - n=subjects who had an assessment at baseline and given time point
[188] - n=subjects who had an assessment at baseline and given time point
[189] - n=subjects who had an assessment at baseline and given time point
[190] - n=subjects who had an assessment at baseline and given time point

No statistical analyses for this end point

Secondary: Percentage of Subjects With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Top of page

End point title

Percentage of Subjects With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

End point description

Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound.

End point type

Secondary

End point timeframe

Baseline, Month 3, Month 6, and Final Visit

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	65 ^[191]	65 ^[192]	64 ^[193]	65 ^[194]	78 ^[195]	77 ^[196]	76 ^[197]	77 ^[198]
Units: percentage of subjects
number (not applicable)
Month 3; n=53, 49, 52, 47, 64, 57, 53, 58	13.2	67.3	46.2	23.4	10.9	63.2	37.7	22.4
Month 6; n=45, 44, 48, 42, 55, 50, 44, 46	24.4	70.5	47.9	26.2	14.5	64	38.6	34.8
Final Visit; n=53, 53, 54, 51, 66, 59, 55, 60	24.5	69.8	50	27.5	13.6	66.1	40	30

Attachments

Untitled (Filename: Table 32_statistical analyses.docx)

Notes
[191] - n=subjects with an assessment at baseline and given time point
[192] - n=subjects with an assessment at baseline and given time point
[193] - n=subjects with an assessment at baseline and given time point
[194] - n=subjects with an assessment at baseline and given time point
[195] - n=subjects with an assessment at baseline and given time point
[196] - n=subjects with an assessment at baseline and given time point
[197] - n=subjects with an assessment at baseline and given time point
[198] - n=subjects with an assessment at baseline and given time point

No statistical analyses for this end point

Secondary: Percentage of Subjects with ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Top of page

End point title

Percentage of Subjects with ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

End point description

Total fibroid volume (3 largest fibroids) was measured by transvaginal ultrasound, or transabdominal ultrasound.

End point type

Secondary

End point timeframe

Baseline, Month 3, Month 6, and Final Visit

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	65 ^[199]	65 ^[200]	64 ^[201]	65 ^[202]	78 ^[203]	77 ^[204]	76 ^[205]	77 ^[206]
Units: percentage of subjects
number (not applicable)
Month 3; n=53, 49, 52, 47, 64, 57, 53, 58	13.2	79.6	50	31.9	9.4	66.7	34	22.4
Month 6; n=45, 44, 48, 42, 55, 50, 44, 46	24.4	75	54.2	40.5	18.2	62	40.9	34.8
Final Visit; n=53, 53, 54, 51, 66, 59, 55, 60	24.5	73.6	57.4	41.2	16.7	64.4	40	30

Attachments

Untitled (Filename: Table 33_statistical analyses.docx)

Notes
[199] - n=subjects with an assessment at baseline and given time point
[200] - n=subjects with an assessment at baseline and given time point
[201] - n=subjects with an assessment at baseline and given time point
[202] - n=subjects with an assessment at baseline and given time point
[203] - n=subjects with an assessment at baseline and given time point
[204] - n=subjects with an assessment at baseline and given time point
[205] - n=subjects with an assessment at baseline and given time point
[206] - n=subjects with an assessment at baseline and given time point

No statistical analyses for this end point

Secondary: Percentage of Subjects with ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Top of page

End point title

Percentage of Subjects with ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

End point description

Uterine volume was measured by transvaginal ultrasound or transabdominal ultrasound.

End point type

Secondary

End point timeframe

Baseline, Month 3, Month 6, and Final Visit

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	65 ^[207]	65 ^[208]	64 ^[209]	65 ^[210]	78 ^[211]	77 ^[212]	76 ^[213]	77 ^[214]
Units: percentage of subjects
number (not applicable)
Month 3; n=58, 52, 56, 54, 72, 63, 57, 63	5.2	73.1	42.9	18.5	1.4	57.1	36.8	17.5
Month 6; n=51, 47, 50, 47, 61, 56, 49, 50	2	78.7	58	31.9	1.6	62.5	32.7	26
Final Visit; n=58, 56, 56, 56, 72, 65, 58, 64	3.4	73.2	58.9	26.8	1.4	63.1	29.3	23.4

Attachments

Untitled (Filename: Table 35_statistical analyses.docx)

Notes
[207] - n=subjects with an assessment at baseline and given time point
[208] - n=subjects with an assessment at baseline and given time point
[209] - n=subjects with an assessment at baseline and given time point
[210] - n=subjects with an assessment at baseline and given time point
[211] - n=subjects with an assessment at baseline and given time point
[212] - n=subjects with an assessment at baseline and given time point
[213] - n=subjects with an assessment at baseline and given time point
[214] - n=subjects with an assessment at baseline and given time point

No statistical analyses for this end point

Secondary: Percentage of Subjects Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids

Top of page

End point title

Percentage of Subjects Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids

End point description

End point type

Secondary

End point timeframe

Month 6

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	0 ^[215]	0 ^[216]	0 ^[217]	0 ^[218]	0 ^[219]	0 ^[220]	0 ^[221]	0 ^[222]
Units: percentage of subjects
number (not applicable)

Notes
[215] - This was not completed due to lack of data collection.
[216] - This was not completed due to lack of data collection.
[217] - This was not completed due to lack of data collection.
[218] - This was not completed due to lack of data collection.
[219] - This was not completed due to lack of data collection.
[220] - This was not completed due to lack of data collection.
[221] - This was not completed due to lack of data collection.
[222] - This was not completed due to lack of data collection.

No statistical analyses for this end point

Secondary: Mean Change in Hemoglobin Concentration from Baseline to Final Visit

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End point title

Mean Change in Hemoglobin Concentration from Baseline to Final Visit

End point description

Baseline is defined as the last measurement prior to the first dose of study drug.

End point type

Secondary

End point timeframe

Baseline, Final Visit during treatment period (Month 6 or early termination)

End point values	Cohort 1: Placebo, mITT	Cohort 1: Elagolix 300 mg BID, mITT	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT	Cohort 2: Placebo, mITT	Cohort 2: Elagolix 600 mg QD, mITT	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT
Number of subjects analysed	64 ^[223]	61 ^[224]	59 ^[225]	61 ^[226]	76 ^[227]	71 ^[228]	72 ^[229]	74 ^[230]
Units: g/dL
least squares mean (standard error)	0.6 ± 0.17	1.9 ± 0.17	1.9 ± 0.17	1.4 ± 0.17	0.3 ± 0.15	1.4 ± 0.16	1.1 ± 0.16	1.2 ± 0.16

Notes
[223] - subjects with an assessment at baseline and final visit
[224] - subjects with an assessment at baseline and final visit
[225] - subjects with an assessment at baseline and final visit
[226] - subjects with an assessment at baseline and final visit
[227] - subjects with an assessment at baseline and final visit
[228] - subjects with an assessment at baseline and final visit
[229] - subjects with an assessment at baseline and final visit
[230] - subjects with an assessment at baseline and final visit

Statistical Analysis 1

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[231]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.74

Variability estimate

Standard error of the mean

Dispersion value

0.24

Notes
[231] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 2

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD, mITT

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[232]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.72

Variability estimate

Standard error of the mean

Dispersion value

0.24

Notes
[232] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 3

Comparison groups

Cohort 1: Placebo, mITT v Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD, mITT

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[233]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

1.27

Variability estimate

Standard error of the mean

Dispersion value

0.24

Notes
[233] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 4

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD, mITT

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[234]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.52

Variability estimate

Standard error of the mean

Dispersion value

0.22

Notes
[234] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 5

Comparison groups

Cohort 2: Placebo, mITT v Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD, mITT

Number of subjects included in analysis

148

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[235]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

1.16

Variability estimate

Standard error of the mean

Dispersion value

0.22

Notes
[235] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Statistical Analysis 6

Comparison groups

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD, mITT v Cohort 2: Placebo, mITT

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[236]

Method

ANCOVA

Parameter type

difference in LS means

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.26

Variability estimate

Standard error of the mean

Dispersion value

0.22

Notes
[236] - P value for test of difference between each elagolix dose group and placebo at each postbaseline time point is from an ANCOVA model with treatment as the main effect and baseline value as a covariate.

Adverse events

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Timeframe for reporting adverse events

From the time of study drug administration through Final Visit (Month 6 or early termination) plus 30 days

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

Cohort 1: Placebo

Reporting group description

Placebo for elagolix and placebo for estradiol/norethindrone acetate (E2/NETA) twice daily (BID)

Reporting group title

Cohort 1: Elagolix 300 mg BID

Reporting group description

Elagolix 300 mg BID alone

Reporting group title

Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD

Reporting group description

Elagolix 300 mg BID plus low-dose (LD) E2/NETA QD once daily (QD)

Reporting group title

Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD

Reporting group description

Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD

Reporting group title

Cohort 2: Placebo

Reporting group description

Placebo for elagolix and E2/NETA QD

Reporting group title

Cohort 2: Elagolix 600 mg QD

Reporting group description

Elagolix 600 mg QD alone

Reporting group title

Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD

Reporting group description

Elagolix 600 mg QD plus LD E2/NETA QD

Reporting group title

Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD

Reporting group description

Elagolix 600 mg QD plus SD E2/NETA QD

Serious adverse events	Cohort 1: Placebo	Cohort 1: Elagolix 300 mg BID	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD	Cohort 2: Placebo	Cohort 2: Elagolix 600 mg QD	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 65 (9.23%)	3 / 65 (4.62%)	3 / 64 (4.69%)	1 / 65 (1.54%)	1 / 78 (1.28%)	5 / 77 (6.49%)	3 / 76 (3.95%)	4 / 77 (5.19%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	1 / 65 (1.54%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endometrial adenocarcinoma
subjects affected / exposed	0 / 65 (0.00%)	1 / 65 (1.54%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrinoma malignant
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	1 / 77 (1.30%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	1 / 64 (1.56%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Concussion
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	1 / 65 (1.54%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 65 (0.00%)	1 / 65 (1.54%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	1 / 64 (1.56%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Coronary artery disease
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	1 / 64 (1.56%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Syncope
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	1 / 65 (1.54%)	1 / 78 (1.28%)	1 / 77 (1.30%)	0 / 76 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	1 / 65 (1.54%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diverticular perforation
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	1 / 77 (1.30%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Cystocele
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	1 / 77 (1.30%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysmenorrhoea
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	1 / 65 (1.54%)	1 / 65 (1.54%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic pain
subjects affected / exposed	1 / 65 (1.54%)	1 / 65 (1.54%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine haemorrhage
subjects affected / exposed	1 / 65 (1.54%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 65 (0.00%)	1 / 65 (1.54%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Neck pain
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	0 / 76 (0.00%)	1 / 77 (1.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	0 / 77 (0.00%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 65 (1.54%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	1 / 77 (1.30%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicella
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	1 / 77 (1.30%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Cohort 1: Placebo	Cohort 1: Elagolix 300 mg BID	Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD	Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD	Cohort 2: Placebo	Cohort 2: Elagolix 600 mg QD	Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD	Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD
Total subjects affected by non serious adverse events
subjects affected / exposed	33 / 65 (50.77%)	45 / 65 (69.23%)	37 / 64 (57.81%)	44 / 65 (67.69%)	42 / 78 (53.85%)	59 / 77 (76.62%)	43 / 76 (56.58%)	51 / 77 (66.23%)
Investigations
Blood cholesterol increased
subjects affected / exposed	1 / 65 (1.54%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	4 / 77 (5.19%)	4 / 76 (5.26%)	2 / 77 (2.60%)
occurrences all number	1	0	0	0	0	4	5	2
Bone density decreased
subjects affected / exposed	1 / 65 (1.54%)	5 / 65 (7.69%)	2 / 64 (3.13%)	1 / 65 (1.54%)	2 / 78 (2.56%)	1 / 77 (1.30%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences all number	1	5	2	1	2	1	1	0
Lipids increased
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	0 / 64 (0.00%)	0 / 65 (0.00%)	0 / 78 (0.00%)	4 / 77 (5.19%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences all number	0	0	0	0	0	4	0	0
Weight increased
subjects affected / exposed	0 / 65 (0.00%)	1 / 65 (1.54%)	1 / 64 (1.56%)	0 / 65 (0.00%)	0 / 78 (0.00%)	6 / 77 (7.79%)	1 / 76 (1.32%)	1 / 77 (1.30%)
occurrences all number	0	1	1	0	0	6	1	1
Vascular disorders
Hot flush
subjects affected / exposed	2 / 65 (3.08%)	29 / 65 (44.62%)	16 / 64 (25.00%)	7 / 65 (10.77%)	4 / 78 (5.13%)	38 / 77 (49.35%)	14 / 76 (18.42%)	11 / 77 (14.29%)
occurrences all number	2	32	16	7	4	39	14	11
Hypertension
subjects affected / exposed	3 / 65 (4.62%)	1 / 65 (1.54%)	1 / 64 (1.56%)	5 / 65 (7.69%)	0 / 78 (0.00%)	5 / 77 (6.49%)	2 / 76 (2.63%)	1 / 77 (1.30%)
occurrences all number	3	1	1	5	0	6	2	1
Nervous system disorders
Dizziness
subjects affected / exposed	3 / 65 (4.62%)	3 / 65 (4.62%)	1 / 64 (1.56%)	3 / 65 (4.62%)	3 / 78 (3.85%)	3 / 77 (3.90%)	4 / 76 (5.26%)	5 / 77 (6.49%)
occurrences all number	3	3	1	3	4	3	5	5
Headache
subjects affected / exposed	6 / 65 (9.23%)	8 / 65 (12.31%)	9 / 64 (14.06%)	13 / 65 (20.00%)	8 / 78 (10.26%)	13 / 77 (16.88%)	11 / 76 (14.47%)	14 / 77 (18.18%)
occurrences all number	7	8	9	14	9	15	11	14
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	6 / 65 (9.23%)	1 / 65 (1.54%)	2 / 64 (3.13%)	2 / 65 (3.08%)	6 / 78 (7.69%)	3 / 77 (3.90%)	6 / 76 (7.89%)	4 / 77 (5.19%)
occurrences all number	6	1	2	2	6	3	6	4
General disorders and administration site conditions
Fatigue
subjects affected / exposed	2 / 65 (3.08%)	3 / 65 (4.62%)	4 / 64 (6.25%)	3 / 65 (4.62%)	3 / 78 (3.85%)	0 / 77 (0.00%)	1 / 76 (1.32%)	5 / 77 (6.49%)
occurrences all number	2	3	4	3	3	0	1	5
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	1 / 65 (1.54%)	1 / 65 (1.54%)	0 / 64 (0.00%)	1 / 65 (1.54%)	3 / 78 (3.85%)	6 / 77 (7.79%)	1 / 76 (1.32%)	3 / 77 (3.90%)
occurrences all number	1	1	0	1	3	6	1	3
Abdominal pain
subjects affected / exposed	2 / 65 (3.08%)	1 / 65 (1.54%)	2 / 64 (3.13%)	2 / 65 (3.08%)	2 / 78 (2.56%)	3 / 77 (3.90%)	3 / 76 (3.95%)	4 / 77 (5.19%)
occurrences all number	2	1	2	2	3	3	3	4
Abdominal pain lower
subjects affected / exposed	0 / 65 (0.00%)	4 / 65 (6.15%)	0 / 64 (0.00%)	0 / 65 (0.00%)	2 / 78 (2.56%)	1 / 77 (1.30%)	0 / 76 (0.00%)	4 / 77 (5.19%)
occurrences all number	0	4	0	0	2	1	0	5
Abdominal pain upper
subjects affected / exposed	0 / 65 (0.00%)	0 / 65 (0.00%)	1 / 64 (1.56%)	0 / 65 (0.00%)	0 / 78 (0.00%)	1 / 77 (1.30%)	0 / 76 (0.00%)	4 / 77 (5.19%)
occurrences all number	0	0	4	0	0	1	0	5
Diarrhoea
subjects affected / exposed	3 / 65 (4.62%)	1 / 65 (1.54%)	2 / 64 (3.13%)	5 / 65 (7.69%)	4 / 78 (5.13%)	5 / 77 (6.49%)	3 / 76 (3.95%)	4 / 77 (5.19%)
occurrences all number	3	1	2	6	4	5	3	5
Nausea
subjects affected / exposed	6 / 65 (9.23%)	4 / 65 (6.15%)	4 / 64 (6.25%)	12 / 65 (18.46%)	3 / 78 (3.85%)	10 / 77 (12.99%)	12 / 76 (15.79%)	20 / 77 (25.97%)
occurrences all number	6	4	4	13	4	11	12	23
Vomiting
subjects affected / exposed	1 / 65 (1.54%)	1 / 65 (1.54%)	0 / 64 (0.00%)	3 / 65 (4.62%)	4 / 78 (5.13%)	4 / 77 (5.19%)	3 / 76 (3.95%)	5 / 77 (6.49%)
occurrences all number	2	1	0	3	5	6	3	7
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	2 / 65 (3.08%)	2 / 65 (3.08%)	1 / 64 (1.56%)	3 / 65 (4.62%)	2 / 78 (2.56%)	2 / 77 (2.60%)	5 / 76 (6.58%)	3 / 77 (3.90%)
occurrences all number	2	2	1	3	2	2	6	4
Menorrhagia
subjects affected / exposed	1 / 65 (1.54%)	2 / 65 (3.08%)	3 / 64 (4.69%)	4 / 65 (6.15%)	2 / 78 (2.56%)	1 / 77 (1.30%)	2 / 76 (2.63%)	7 / 77 (9.09%)
occurrences all number	1	2	3	6	2	1	2	8
Pelvic pain
subjects affected / exposed	0 / 65 (0.00%)	2 / 65 (3.08%)	1 / 64 (1.56%)	3 / 65 (4.62%)	1 / 78 (1.28%)	0 / 77 (0.00%)	1 / 76 (1.32%)	5 / 77 (6.49%)
occurrences all number	0	2	1	3	1	0	1	5
Psychiatric disorders
Insomnia
subjects affected / exposed	1 / 65 (1.54%)	7 / 65 (10.77%)	5 / 64 (7.81%)	0 / 65 (0.00%)	2 / 78 (2.56%)	4 / 77 (5.19%)	2 / 76 (2.63%)	5 / 77 (6.49%)
occurrences all number	1	7	5	0	2	4	2	5
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 65 (4.62%)	3 / 65 (4.62%)	3 / 64 (4.69%)	0 / 65 (0.00%)	3 / 78 (3.85%)	5 / 77 (6.49%)	4 / 76 (5.26%)	1 / 77 (1.30%)
occurrences all number	3	6	3	0	3	5	4	1
Back pain
subjects affected / exposed	6 / 65 (9.23%)	5 / 65 (7.69%)	2 / 64 (3.13%)	3 / 65 (4.62%)	2 / 78 (2.56%)	6 / 77 (7.79%)	6 / 76 (7.89%)	7 / 77 (9.09%)
occurrences all number	6	5	2	3	2	7	7	7
Muscle spasms
subjects affected / exposed	2 / 65 (3.08%)	0 / 65 (0.00%)	1 / 64 (1.56%)	2 / 65 (3.08%)	2 / 78 (2.56%)	5 / 77 (6.49%)	1 / 76 (1.32%)	3 / 77 (3.90%)
occurrences all number	2	0	1	2	4	5	1	3
Musculoskeletal pain
subjects affected / exposed	1 / 65 (1.54%)	4 / 65 (6.15%)	1 / 64 (1.56%)	0 / 65 (0.00%)	0 / 78 (0.00%)	3 / 77 (3.90%)	0 / 76 (0.00%)	0 / 77 (0.00%)
occurrences all number	1	4	1	0	0	3	0	0
Pain in extremity
subjects affected / exposed	2 / 65 (3.08%)	4 / 65 (6.15%)	2 / 64 (3.13%)	4 / 65 (6.15%)	0 / 78 (0.00%)	2 / 77 (2.60%)	1 / 76 (1.32%)	2 / 77 (2.60%)
occurrences all number	2	4	2	4	0	2	1	2
Infections and infestations
Bacterial vaginosis
subjects affected / exposed	4 / 65 (6.15%)	4 / 65 (6.15%)	4 / 64 (6.25%)	1 / 65 (1.54%)	2 / 78 (2.56%)	2 / 77 (2.60%)	1 / 76 (1.32%)	0 / 77 (0.00%)
occurrences all number	4	6	5	1	2	2	1	0
Nasopharyngitis
subjects affected / exposed	4 / 65 (6.15%)	3 / 65 (4.62%)	4 / 64 (6.25%)	0 / 65 (0.00%)	1 / 78 (1.28%)	2 / 77 (2.60%)	3 / 76 (3.95%)	4 / 77 (5.19%)
occurrences all number	4	3	4	0	1	2	3	5
Sinusitis
subjects affected / exposed	0 / 65 (0.00%)	2 / 65 (3.08%)	2 / 64 (3.13%)	2 / 65 (3.08%)	5 / 78 (6.41%)	2 / 77 (2.60%)	2 / 76 (2.63%)	1 / 77 (1.30%)
occurrences all number	0	2	2	2	5	2	2	1
Upper respiratory tract infection
subjects affected / exposed	1 / 65 (1.54%)	3 / 65 (4.62%)	1 / 64 (1.56%)	1 / 65 (1.54%)	0 / 78 (0.00%)	4 / 77 (5.19%)	2 / 76 (2.63%)	2 / 77 (2.60%)
occurrences all number	2	3	1	2	0	6	2	2
Urinary tract infection
subjects affected / exposed	2 / 65 (3.08%)	2 / 65 (3.08%)	5 / 64 (7.81%)	4 / 65 (6.15%)	5 / 78 (6.41%)	1 / 77 (1.30%)	2 / 76 (2.63%)	2 / 77 (2.60%)
occurrences all number	2	3	7	4	5	1	2	2
Vulvovaginal mycotic infection
subjects affected / exposed	1 / 65 (1.54%)	0 / 65 (0.00%)	2 / 64 (3.13%)	4 / 65 (6.15%)	2 / 78 (2.56%)	1 / 77 (1.30%)	0 / 76 (0.00%)	2 / 77 (2.60%)
occurrences all number	1	0	3	4	2	1	0	2

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Were there any global substantial amendments to the protocol? Yes

20 Aug 2013

● Removed baseline observation carried forward method (BOCF) from the repeat primary analysis when imputing subjects who prematurely discontinued prior to Month 6. ● Defined treatment-emergent AEs and updated per treatment group the events that were calculated. ● Changed sample size from 70 subjects per treatment group to 65 and added 260 subjects for Cohort 2, increasing the total number of subjects to 520.

15 Aug 2014

● Clarified statistical analysis of primary and secondary efficacy endpoints

20 Apr 2015

● Clarified when the end-of-treatment-period analyses was conducted, added an interim analysis of Cohort 2 for internal planning purposes, and clarified the statistical analysis of primary and secondary efficacy endpoints.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With a MBL Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

Primary: Percentage of Participants With a MBL Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

Secondary: Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 days of Treatment

Secondary: Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 days of Treatment

Secondary: Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 days of Treatment

Secondary: Percentage of Subjects With a MBL volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 days of Treatment

Secondary: Percentage of Subjects Who Achieved an MBL Volume of < 80 mL at the Final Month

Secondary: Percentage of Subjects Who Achieved an MBL Volume of < 80 mL at the Final Month

Secondary: Percentage of Subjects With a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

Secondary: Percentage of Subjects With a ≥ 50% Reduction in MBL Volume from Baseline to the Final Month

Secondary: Percentage of Subjects Who Achieved Amenorrhea During the Last 56 Days of Treatment

Secondary: Percentage of Subjects Who Achieved Amenorrhea During the Last 56 Days of Treatment

Secondary: Percentage of Subjects Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment

Secondary: Percentage of Subjects Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment

Secondary: Mean Change in the Number of Bleeding Days from Baseline to Month 6

Secondary: Mean Change in the Number of Bleeding Days from Baseline to Month 6

Secondary: Mean Change in the Number of Heavy Bleeding Days from Baseline to Month 6

Secondary: Mean Change in the Number of Heavy Bleeding Days from Baseline to Month 6

Secondary: Change in Bleeding Severity Scores From Baseline at the Final Month

Secondary: Change in Bleeding Severity Scores From Baseline at the Final Month

Secondary: Change from Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire

Secondary: Change from Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire

Secondary: Mean Percentage Change from Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Mean Percentage Change from Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Mean Percentage Change from Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Mean Percentage Change from Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Mean Percentage Change from Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Secondary: Mean Percentage Change from Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Secondary: Percentage of Subjects With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Percentage of Subjects With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Percentage of Subjects with ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Percentage of Subjects with ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit

Secondary: Percentage of Subjects with ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Secondary: Percentage of Subjects with ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit

Secondary: Percentage of Subjects Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids

Secondary: Percentage of Subjects Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids

Secondary: Mean Change in Hemoglobin Concentration from Baseline to Final Visit

Secondary: Mean Change in Hemoglobin Concentration from Baseline to Final Visit

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women with Heavy Menstrual Bleeding Associated with Uterine Fibroids