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Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01441635
Recruitment Status : Completed
First Posted : September 28, 2011
Results First Posted : July 15, 2020
Last Update Posted : July 15, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Heavy Uterine Bleeding
Uterine Fibroids
Interventions Drug: Elagolix
Drug: Placebo
Drug: Estradiol/Norethindrone acetate (E2/NETA)
Drug: Estradiol
Drug: Progesterone
Enrollment 271
Recruitment Details Overall, 271 female participants were enrolled into the study across 45 sites in the United States.
Pre-assignment Details Six cohorts of participants were enrolled, with 3 double-blind cohorts comparing elagolix with placebo, 2 open-label cohorts assessing add-back therapies, and 1 open-label cohort assessing the elagolix 600 mg QD dosing regimen.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description Participants received elagolix 400 mg once a day (QD) for 3 months. Participants received elagolix 100 mg twice a day (BID) for 3 months. Participants received placebo to elagolix BID for 3 months. Participants received elagolix 200 mg twice a day for 3 months. Participants received placebo to elagolix twice a day for 3 months. Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months. Participants received elagolix 600 mg once a day for 3 months. Participants received elagolix 300 mg twice a day for 3 months. Participants received placebo to elagolix BID for 3 months. Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Period Title: Overall Study
Started 32 33 16 35 18 34 30 30 16 27
Completed 26 27 13 28 16 29 24 26 14 25
Not Completed 6 6 3 7 2 5 6 4 2 2
Reason Not Completed
Adverse Event             4             3             1             5             1             2             2             2             1             0
Withdrawal by Subject             1             1             0             1             0             0             2             0             1             1
Lost to Follow-up             0             1             1             1             1             3             1             1             0             1
Noncompliance             0             1             0             0             0             0             1             0             0             0
Surgery or Invasive Intervention             0             0             1             0             0             0             0             0             0             0
Received Exclusionary Medication             1             0             0             0             0             0             0             0             0             0
Other             0             0             0             0             0             0             0             1             0             0
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP Total
Hide Arm/Group Description Participants received elagolix 400 mg once a day (QD) for 3 months. Participants received elagolix 100 mg twice a day (BID) for 3 months. Participants received placebo to elagolix BID for 3 months. Participants received elagolix 200 mg twice a day for 3 months. Participants received placebo to elagolix twice a day for 3 months. Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months. Participants received elagolix 600 mg once a day for 3 months. Participants received elagolix 300 mg twice a day for 3 months. Participants received placebo to elagolix BID for 3 months. Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months. Total of all reporting groups
Overall Number of Baseline Participants 32 33 16 35 18 34 30 30 16 27 271
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 33 participants 16 participants 35 participants 18 participants 34 participants 30 participants 30 participants 16 participants 27 participants 271 participants
40.8  (5.50) 42.1  (5.09) 41.1  (5.88) 43.1  (4.29) 44.0  (4.24) 40.9  (6.02) 40.8  (5.78) 42.6  (5.55) 41.6  (7.10) 41.6  (5.26) 41.8  (5.4)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 33 participants 16 participants 35 participants 18 participants 34 participants 30 participants 30 participants 16 participants 27 participants 271 participants
< 35 years
7
  21.9%
3
   9.1%
2
  12.5%
2
   5.7%
0
   0.0%
5
  14.7%
4
  13.3%
3
  10.0%
3
  18.8%
3
  11.1%
32
  11.8%
35 to < 40 years
6
  18.8%
5
  15.2%
5
  31.3%
5
  14.3%
2
  11.1%
8
  23.5%
6
  20.0%
5
  16.7%
3
  18.8%
6
  22.2%
51
  18.8%
40 to < 45 years
8
  25.0%
13
  39.4%
2
  12.5%
13
  37.1%
7
  38.9%
10
  29.4%
11
  36.7%
9
  30.0%
3
  18.8%
10
  37.0%
86
  31.7%
≥ 45 years
11
  34.4%
12
  36.4%
7
  43.8%
15
  42.9%
9
  50.0%
11
  32.4%
9
  30.0%
13
  43.3%
7
  43.8%
8
  29.6%
102
  37.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 33 participants 16 participants 35 participants 18 participants 34 participants 30 participants 30 participants 16 participants 27 participants 271 participants
Female
32
 100.0%
33
 100.0%
16
 100.0%
35
 100.0%
18
 100.0%
34
 100.0%
30
 100.0%
30
 100.0%
16
 100.0%
27
 100.0%
271
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 33 participants 16 participants 35 participants 18 participants 34 participants 30 participants 30 participants 16 participants 27 participants 271 participants
Hispanic or Latino
1
   3.1%
8
  24.2%
1
   6.3%
1
   2.9%
1
   5.6%
1
   2.9%
6
  20.0%
0
   0.0%
2
  12.5%
12
  44.4%
33
  12.2%
Not Hispanic or Latino
31
  96.9%
25
  75.8%
15
  93.8%
34
  97.1%
17
  94.4%
33
  97.1%
24
  80.0%
30
 100.0%
14
  87.5%
15
  55.6%
238
  87.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 33 participants 16 participants 35 participants 18 participants 34 participants 30 participants 30 participants 16 participants 27 participants 271 participants
White
5
  15.6%
10
  30.3%
3
  18.8%
7
  20.0%
3
  16.7%
7
  20.6%
5
  16.7%
6
  20.0%
6
  37.5%
11
  40.7%
63
  23.2%
Black
25
  78.1%
23
  69.7%
13
  81.3%
28
  80.0%
14
  77.8%
26
  76.5%
24
  80.0%
23
  76.7%
9
  56.3%
15
  55.6%
200
  73.8%
Asian
1
   3.1%
0
   0.0%
0
   0.0%
0
   0.0%
1
   5.6%
1
   2.9%
0
   0.0%
0
   0.0%
1
   6.3%
0
   0.0%
4
   1.5%
Other
1
   3.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.3%
1
   3.3%
0
   0.0%
0
   0.0%
3
   1.1%
Multirace
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
1
   0.4%
1.Primary Outcome
Title Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
Hide Description

The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.

Time Frame Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. Last observation carried forward (LOCF) imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 31 31 15 32 18 33 28 30 15 26
Mean (Standard Deviation)
Unit of Measure: mL
Baseline 213.70  (108.08) 269.36  (163.17) 321.73  (327.57) 335.11  (322.68) 251.72  (160.29) 247.70  (177.72) 215.62  (122.84) 206.27  (125.08) 349.17  (424.12) 257.99  (207.33)
Change from Baseline -183.97  (132.19) -184.69  (187.05) -10.46  (85.04) -272.97  (271.39) -79.00  (161.33) -192.33  (191.51) -189.05  (151.15) -202.57  (127.93) -175.31  (342.14) -216.15  (157.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -205.9
Confidence Interval (2-Sided) 95%
-295.77 to -116.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 45.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -189.9
Confidence Interval (2-Sided) 95%
-278.33 to -101.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 44.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -138.0
Confidence Interval (2-Sided) 95%
-220.18 to -55.76
Parameter Dispersion
Type: Standard Error of the Mean
Value: 40.86
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -130.6
Confidence Interval (2-Sided) 95%
-206.70 to -54.60
Parameter Dispersion
Type: Standard Error of the Mean
Value: 37.68
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
Hide Description

The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.

Time Frame Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. Last observation carried forward (LOCF) imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the electronic diary.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 31 31 15 32 18 33 28 30 15 26
Mean (Standard Deviation)
Unit of Measure: percent change
-83.83  (35.23) -71.85  (49.20) -6.98  (40.78) -81.03  (55.77) -11.12  (103.11) -79.60  (43.63) -88.58  (39.58) -97.31  (12.57) -42.64  (39.68) -85.39  (28.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -75.60
Confidence Interval (2-Sided) 95%
-102.93 to -48.28
Parameter Dispersion
Type: Standard Error of the Mean
Value: 13.71
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -64.27
Confidence Interval (2-Sided) 95%
-91.14 to -37.39
Parameter Dispersion
Type: Standard Error of the Mean
Value: 13.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -67.67
Confidence Interval (2-Sided) 95%
-113.39 to -21.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 22.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS mean Difference
Estimated Value -56.84
Confidence Interval (2-Sided) 95%
-73.24 to -40.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 8.12
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
Hide Description

The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.

Time Frame Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 31 31 15 33 18 33 28 30 15 26
Measure Type: Number
Unit of Measure: percentage of participants
84 74 13 85 17 85 93 97 33 85
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment
Hide Description

The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.

Time Frame The last 28 days of treatment (approximately days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 31 31 15 33 18 33 28 30 15 26
Measure Type: Number
Unit of Measure: percentage of participants
84 74 13 85 22 88 93 97 47 88
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
Hide Description

The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.

Time Frame Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 31 31 15 33 18 33 28 30 15 26
Measure Type: Number
Unit of Measure: percentage of participants
84 74 13 91 28 85 93 97 40 88
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3
Hide Description

The percentage of subjects with changes in hemoglobin concentration from Baseline to Month 3 in each of the following categories:

  • No change from baseline in hemoglobin
  • Decrease from baseline in hemoglobin ≥ -0.5 g/dL
  • Decrease from baseline in hemoglobin ≥ -1.0 g/dL
  • Increase from baseline in hemoglobin ≥ 0.5 g/dL
  • Increase from baseline in hemoglobin ≥ 1.0 g/dL

The above categories are not all mutually exclusive or exhaustive.

Time Frame Baseline and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available hemoglobin data.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 23 24 11 27 14 28 23 25 14 21
Measure Type: Number
Unit of Measure: percentage of participants
No Change 0 0 9 0 0 0 4 0 0 5
Decreases from -0.5 to 0 g/dL 9 17 0 4 21 14 4 0 21 5
Decreases from -1.0 to -0.5 g/dL 4 4 27 11 14 0 4 0 7 10
Increase ≥ 0.5 g/dL 78 71 18 67 29 75 83 76 29 71
Increase ≥ 1.0 g/dL 61 71 9 59 29 43 57 52 29 62
7.Secondary Outcome
Title Change in Hemoglobin Concentration From Baseline to Month 3
Hide Description [Not Specified]
Time Frame Baseline and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available hemoglobin data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 23 24 11 27 14 28 23 25 14 21
Mean (Standard Deviation)
Unit of Measure: g/dL
1.18  (0.99) 1.30  (1.19) -0.43  (1.28) 1.13  (1.29) 0.28  (1.33) 0.92  (0.81) 1.40  (1.18) 1.19  (0.85) 0.31  (1.20) 1.54  (1.81)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
0.97 to 2.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
1.00 to 2.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
0.13 to 1.75
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
0.28 to 1.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.30
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline to Month 3 in Uterine Bleeding Score
Hide Description

Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.
Time Frame Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 30 30 15 32 17 32 26 27 15 25
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.50  (0.56) -0.37  (0.46) -0.19  (0.33) -0.52  (0.65) -0.22  (0.32) -0.24  (0.47) -0.44  (0.71) -0.53  (0.33) -0.38  (0.77) -0.25  (0.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.63 to -0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.59 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.59 to 0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.80 to -0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.15
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding
Hide Description

Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

A day with any uterine bleeding is defined as a days with a bleeding score ≥ 1.

Time Frame Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 30 30 15 32 17 32 26 27 15 25
Mean (Standard Deviation)
Unit of Measure: percentage of days
-15.22  (14.77) -11.00  (15.52) -5.78  (10.58) -15.82  (17.88) -6.99  (12.82) 3.63  (24.74) -15.38  (23.21) -16.91  (11.13) -13.95  (23.83) 1.73  (26.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -10.29
Confidence Interval (2-Sided) 95%
-18.90 to -1.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.087
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -7.62
Confidence Interval (2-Sided) 95%
-16.36 to 1.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.39
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -8.81
Confidence Interval (2-Sided) 95%
-17.43 to -0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -13.69
Confidence Interval (2-Sided) 95%
-22.06 to -5.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.14
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding
Hide Description

Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

A day with moderate to very heavy bleeding is defined as a days with a bleeding score ≥ 3.

Time Frame Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 30 30 15 32 17 32 26 27 15 25
Mean (Standard Deviation)
Unit of Measure: percentage of days
-7.22  (9.27) -5.00  (7.87) -4.00  (5.37) -7.03  (10.89) -3.08  (5.88) -7.92  (6.43) -6.15  (8.47) -8.02  (5.41) -3.31  (10.40) -6.80  (10.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.51
Confidence Interval (2-Sided) 95%
-9.56 to -1.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.95
Confidence Interval (2-Sided) 95%
-9.11 to -0.80
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.63
Confidence Interval (2-Sided) 95%
-9.18 to 1.91
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.75
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline as a covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -7.20
Confidence Interval (2-Sided) 95%
-11.33 to -3.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.04
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3
Hide Description

Participants recorded the previous days' presence and severity of bleeding every morning in an eDiary according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

  • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
  • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
  • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
  • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
  • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
  • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

Any bleeding is defined as a score ≥ 1 and moderate to very heavy bleeding is defined as a score ≥ 3.

Time Frame Month 3 (average bleeding score over days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 30 30 15 32 17 32 26 27 15 26
Measure Type: Number
Unit of Measure: percentage of participants
Any bleeding 37 57 93 47 94 78 27 26 80 69
Moderate to Very Heavy Bleeding 27 40 87 28 82 31 15 7 73 35
12.Secondary Outcome
Title Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment
Hide Description

Suppression of bleeding is defined as no record of bleeding (spotting allowed) in the e-diary and no record of bleeding Indicated in the alkaline hematin data during the last 56 days of treatment.

Amenorrhea is defined as no record of bleeding or spotting indicated in the e-diary and no record of bleeding or spotting Indicated in the alkaline hematin data during the last 56 days of treatment.

Time Frame The last 56 days of treatment (approximately days 33 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants including participants with less than 56 days of treatment who bled but excluded those who did not bleed.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 30 29 15 32 18 32 26 29 16 26
Measure Type: Number
Unit of Measure: percentage of participants
Suppression of bleeding 66 45 0 66 0 31 77 79 0 32
Amenorrhea 60 31 0 44 0 19 73 66 0 19
13.Secondary Outcome
Title Percent Change From Baseline to Month 3 in Uterine Volume
Hide Description Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame Baseline and month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 22 20 9 22 12 22 20 20 12 11
Mean (Standard Deviation)
Unit of Measure: percent change
-21.01  (26.79) -21.37  (24.84) 18.72  (15.59) -21.68  (29.80) -8.62  (20.58) -17.43  (19.51) -27.99  (23.34) -33.25  (16.55) -1.92  (17.52) -10.06  (30.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.052
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor.
14.Secondary Outcome
Title Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit
Hide Description Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 30 30 15 31 18 33 27 29 15 24
Measure Type: Number
Unit of Measure: percentage of participants
53 43 7 48 11 42 56 69 7 25
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
15.Secondary Outcome
Title Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
Hide Description The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame Baseline and month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available fibroid volume data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 19 18 9 22 12 22 18 20 12 10
Mean (Standard Deviation)
Unit of Measure: percent change
14.23  (187.83) -22.19  (51.14) -7.26  (36.35) -38.52  (41.72) -2.05  (71.83) -25.77  (46.64) -16.60  (39.61) -35.79  (24.49) 6.70  (45.42) -4.94  (100.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.161
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.173
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Kruskal-Wallis
Comments One-way Kruskal-Wallis test with treatment as a factor.
16.Secondary Outcome
Title Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit
Hide Description The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time Frame Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 28 29 15 31 17 33 25 29 15 21
Measure Type: Number
Unit of Measure: percentage of participants
57 52 33 68 35 58 60 55 27 48
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 400 mg QD, Cohort 4 Elagolix 100 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.203
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 4 Elagolix 100 mg BID, Cohort 4 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.342
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1 Elagolix 200 mg BID, Cohort 1 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 2 Elagolix 300 mg BID, Cohort 2 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.111
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
17.Secondary Outcome
Title Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
Hide Description

The UFS-QoL is a disease-specific, self-administered, validated questionnaire developed to evaluate the symptoms associated with uterine fibroids and their impact on health-related quality of life (HRQL) in women with symptomatic uterine fibroids. The questionnaire consists of 37 questions, divided into 2 parts: 1) an 8-item symptom severity scale and 2) a 29-item HRQL subscale comprising 6 domains (concern, activities, energy/mood, control, self-consiousness, and sexual function), with a 4-week recall. All items are scored on a 5-point scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores were summed and transformed into a 0 to 100 point scale to provide a total score for each of the 2 components.

Lower symptom severity scores indicate better quality of life and higher total HRQL scores indicate better quality of life.

Time Frame Baseline and month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available UFS-QoL data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 23 21 9 26 13 22 20 25 13 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Symptom severity Number Analyzed 23 participants 21 participants 9 participants 26 participants 13 participants 22 participants 20 participants 25 participants 13 participants 14 participants
-39.0  (24.70) -33.2  (28.17) -19.6  (32.80) -31.6  (28.87) -21.4  (20.63) -20.3  (25.35) -36.4  (24.74) -44.1  (22.12) -12.0  (22.49) -39.1  (24.09)
HRQL total Number Analyzed 22 participants 21 participants 9 participants 25 participants 13 participants 22 participants 20 participants 25 participants 13 participants 14 participants
35.3  (21.87) 29.1  (30.96) 16.3  (30.43) 36.0  (27.91) 18.3  (36.66) 28.6  (24.12) 29.9  (30.72) 33.5  (29.42) 11.0  (20.90) 33.1  (30.34)
18.Secondary Outcome
Title Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores
Hide Description The uterine fibroid daily symptom scale is self-administered questionnaire, with a scale that ranges from 0 to 10 for the symptoms of pelvic pain, fatigue, and cramping and the impact of uterine fibroids on the subject's daily life, with 0 being the absence of the symptom and 10 being the worst severity of the symptoms or completely preventing the subjects from performing daily activities. Participants self-reported values daily in the e-Diary.
Time Frame Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 18 18 9 18 11 22 16 20 9 11
Mean (Standard Deviation)
Unit of Measure: units on a scale
Pelvic pain -1.0  (2.27) -0.2  (2.39) -0.3  (1.45) -0.6  (1.75) -1.4  (1.62) -1.1  (1.35) -0.9  (2.15) -1.0  (1.75) -1.2  (1.73) -2.4  (3.00)
Fatigue -0.5  (1.26) -0.0  (2.23) -0.6  (1.45) -0.6  (1.29) -0.5  (1.69) -1.2  (1.92) -1.0  (2.57) -1.5  (1.16) -0.5  (2.88) -2.1  (3.11)
Menstrual cramping -1.2  (1.31) -0.7  (2.51) -0.5  (1.55) -0.9  (1.16) -1.2  (0.80) -0.9  (1.25) -1.1  (1.35) -1.2  (1.09) -1.0  (2.33) -1.3  (2.15)
Impact of uterine fibroids -1.1  (1.18) -0.4  (1.86) -0.8  (1.40) -1.0  (1.37) -1.0  (1.81) -0.9  (1.62) -1.7  (2.41) -1.3  (1.11) -1.0  (2.18) -3.1  (2.78)
19.Secondary Outcome
Title Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
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The Subject Intention Questionnaire (SSIQ) is a non-validated, exploratory questionnaires intended to evaluate the subject's intent to undergo surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to consider surgery) to 10 (very likely to consider surgery).

SSIQ included the 2 following questions:

  1. How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now?
  2. How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?
Time Frame Baseline and month 3
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Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 23 21 9 9 6 22 20 25 13 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Likelihood of having myomectomy Number Analyzed 23 participants 21 participants 9 participants 9 participants 6 participants 22 participants 20 participants 25 participants 13 participants 14 participants
-1.2  (3.68) -3.1  (4.52) 1.0  (2.12) -1.8  (4.70) 2.3  (5.35) -1.4  (4.34) -1.7  (4.18) -0.6  (5.10) 0.4  (4.16) 0.1  (2.63)
Likelihood of having hysterectomy Number Analyzed 23 participants 20 participants 9 participants 9 participants 6 participants 22 participants 20 participants 25 participants 13 participants 14 participants
0.0  (4.04) -1.9  (4.19) 2.0  (3.64) -0.8  (4.91) -0.3  (0.52) -0.7  (3.10) -0.8  (4.42) 0.2  (3.65) 0.0  (1.96) -1.5  (3.92)
20.Secondary Outcome
Title Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
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The Physician Intention Questionnaire (PSIQ) is a non-validated, exploratory questionnaire intended to evaluate the investigator's intent to recommend surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to recommend surgery) to 10 (very likely to recommend surgery).

The PSIQ included the 2 following questions:

  1. How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now?
  2. How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?
Time Frame Baseline and month 3
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Hide Analysis Population Description
Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
Arm/Group Title Cohort 4 Elagolix 400 mg QD Cohort 4 Elagolix 100 mg BID Cohort 4 Placebo Cohort 1 Elagolix 200 mg BID Cohort 1 Placebo Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 5 Elagolix 600 mg QD Cohort 2 Elagolix 300 mg BID Cohort 2 Placebo Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description:
Participants received elagolix 400 mg once a day (QD) for 3 months.
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 200 mg twice a day for 3 months.
Participants received placebo to elagolix twice a day for 3 months.
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Participants received elagolix 600 mg once a day for 3 months.
Participants received elagolix 300 mg twice a day for 3 months.
Participants received placebo to elagolix BID for 3 months.
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Overall Number of Participants Analyzed 23 21 9 9 7 22 20 24 13 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Likelihood to recommend myomectomy -0.9  (2.86) -1.3  (3.31) -2.7  (3.53) -0.8  (1.76) 0.7  (1.11) -0.6  (2.97) -1.3  (3.62) -1.2  (3.59) 0.0  (3.25) 0.0  (3.94)
Likelihood to recommend hysterectomy -0.8  (3.34) -1.8  (4.37) -0.2  (3.15) -2.2  (2.82) 0.4  (1.62) -1.4  (3.08) -2.3  (3.99) -1.5  (3.96) -0.6  (2.81) -2.8  (2.98)
Time Frame From the date of the first dose of study drug through up to 30 days after the last dose of study drug, up to 4 months.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
Hide Arm/Group Description Participants received placebo to elagolix twice a day for 3 months. Participants received elagolix 200 mg twice a day for 3 months. Participants received placebo to elagolix BID for 3 months. Participants received elagolix 300 mg twice a day for 3 months Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months. Participants received placebo to elagolix BID for 3 months. Participants received elagolix 100 mg twice a day (BID) for 3 months. Participants received elagolix 400 mg once a day (QD) for 3 months. Participants received elagolix 600 mg once a day for 3 months. Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
All-Cause Mortality
Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)      0/35 (0.00%)      0/16 (0.00%)      0/30 (0.00%)      0/34 (0.00%)      0/16 (0.00%)      0/33 (0.00%)      0/32 (0.00%)      0/30 (0.00%)      0/27 (0.00%)    
Hide Serious Adverse Events
Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/18 (5.56%)      0/35 (0.00%)      0/16 (0.00%)      1/30 (3.33%)      0/34 (0.00%)      2/16 (12.50%)      2/33 (6.06%)      0/32 (0.00%)      2/30 (6.67%)      0/27 (0.00%)    
Blood and lymphatic system disorders                     
ANAEMIA  1  1/18 (5.56%)  1 0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  2/16 (12.50%)  2 0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Gastrointestinal disorders                     
PANCREATITIS  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  1/30 (3.33%)  1 0/27 (0.00%) 
General disorders                     
NECROSIS  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  1/33 (3.03%)  1 0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Hepatobiliary disorders                     
CHOLECYSTITIS  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  1/33 (3.03%)  1 0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Metabolism and nutrition disorders                     
HYPOVOLAEMIA  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  1/16 (6.25%)  1 0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
UTERINE LEIOMYOMA  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  1/30 (3.33%)  1 0/34 (0.00%)  0/16 (0.00%)  1/33 (3.03%)  1 0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Reproductive system and breast disorders                     
UTERINE HAEMORRHAGE  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  1/33 (3.03%)  1 0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Surgical and medical procedures                     
ABORTION INDUCED  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  1/30 (3.33%)  1 0/27 (0.00%) 
1
Term from vocabulary, MedDRA (16.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1 Placebo Cohort 1 Elagolix 200 mg BID Cohort 2 Placebo Cohort 2 Elagolix 300 mg BID Cohort 3 Elagolix 200 mg BID + LD E2/NETA Cohort 4 Placebo Cohort 4 Elagolix 100 mg BID Cohort 4 Golix 400 mg QD Cohort 5 Elagolix 600 mg QD Cohort 6 Elagolix 300 mg BID + CEP
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/18 (44.44%)      26/35 (74.29%)      10/16 (62.50%)      20/30 (66.67%)      20/34 (58.82%)      9/16 (56.25%)      20/33 (60.61%)      24/32 (75.00%)      22/30 (73.33%)      11/27 (40.74%)    
Blood and lymphatic system disorders                     
ANAEMIA  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 1/30 (3.33%)  1 0/34 (0.00%)  1/16 (6.25%)  1 2/33 (6.06%)  2 0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
LEUKOCYTOSIS  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Gastrointestinal disorders                     
ABDOMINAL PAIN  1  1/18 (5.56%)  1 2/35 (5.71%)  2 0/16 (0.00%)  3/30 (10.00%)  5 0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  2/30 (6.67%)  2 4/27 (14.81%)  5
NAUSEA  1  0/18 (0.00%)  3/35 (8.57%)  4 2/16 (12.50%)  2 2/30 (6.67%)  2 0/34 (0.00%)  1/16 (6.25%)  1 0/33 (0.00%)  5/32 (15.63%)  5 9/30 (30.00%)  9 4/27 (14.81%)  4
ABDOMINAL DISCOMFORT  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 1/30 (3.33%)  1 0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
ABDOMINAL DISTENSION  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  2/30 (6.67%)  2 0/34 (0.00%)  1/16 (6.25%)  1 1/33 (3.03%)  1 0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
ABDOMINAL PAIN LOWER  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  2/30 (6.67%)  2 0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
CONSTIPATION  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  2/16 (12.50%)  2 0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
DIARRHOEA  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 1/30 (3.33%)  1 0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  3/30 (10.00%)  3 3/27 (11.11%)  3
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  2/16 (12.50%)  2 0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
VOMITING  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 1/30 (3.33%)  2 0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  2/30 (6.67%)  2 0/27 (0.00%) 
DRY MOUTH  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  2/32 (6.25%)  2 0/30 (0.00%)  0/27 (0.00%) 
PEPTIC ULCER  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  1/16 (6.25%)  1 0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
General disorders                     
FATIGUE  1  1/18 (5.56%)  1 2/35 (5.71%)  2 0/16 (0.00%)  0/30 (0.00%)  4/34 (11.76%)  4 0/16 (0.00%)  1/33 (3.03%)  1 4/32 (12.50%)  4 2/30 (6.67%)  2 0/27 (0.00%) 
OEDEMA PERIPHERAL  1  1/18 (5.56%)  1 0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  2/32 (6.25%)  2 0/30 (0.00%)  0/27 (0.00%) 
CHILLS  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
INFLUENZA LIKE ILLNESS  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
IRRITABILITY  1  0/18 (0.00%)  0/35 (0.00%)  2/16 (12.50%)  2 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
MALAISE  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
VESSEL PUNCTURE SITE PAIN  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
Immune system disorders                     
HYPERSENSITIVITY  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  2/27 (7.41%)  2
Infections and infestations                     
BRONCHITIS  1  1/18 (5.56%)  1 0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  2/34 (5.88%)  2 0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
VAGINITIS BACTERIAL  1  1/18 (5.56%)  1 1/35 (2.86%)  1 1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
FUNGAL INFECTION  1  0/18 (0.00%)  0/35 (0.00%)  2/16 (12.50%)  2 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
VULVOVAGINITIS  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
FURUNCLE  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  1/16 (6.25%)  1 0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
INFECTED BITES  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  1/16 (6.25%)  1 0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
NASOPHARYNGITIS  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  2/32 (6.25%)  2 0/30 (0.00%)  0/27 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  2/32 (6.25%)  2 2/30 (6.67%)  2 0/27 (0.00%) 
URINARY TRACT INFECTION  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  1/33 (3.03%)  1 3/32 (9.38%)  3 0/30 (0.00%)  0/27 (0.00%) 
Injury, poisoning and procedural complications                     
LACERATION  1  0/18 (0.00%)  0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  2/30 (6.67%)  2 0/27 (0.00%) 
Investigations                     
BLOOD PRESSURE INCREASED  1  1/18 (5.56%)  1 0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  2/27 (7.41%)  2
WEIGHT INCREASED  1  1/18 (5.56%)  1 0/35 (0.00%)  0/16 (0.00%)  0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%) 
BLOOD GLUCOSE INCREASED  1  0/18 (0.00%)  0/35 (0.00%)  1/16 (6.25%)  1 0/30 (0.00%)  0/34 (0.00%)  0/16 (0.00%)  0/33 (0.00%)  0/32 (0.00%)  0/30 (0.00%)  0/27 (0.00%)