Clinical Trial Results:
SPIRIT 2: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Administered with and without Low-Dose Estradiol and Norethindrone Acetate in Women with Endometriosis-Associated Pain
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Summary
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EudraCT number |
2017-001632-19 |
Trial protocol |
SE CZ PL GB IT RO |
Global end of trial date |
31 May 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Sep 2022
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First version publication date |
18 Sep 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MVT-601-3102
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03204331 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Myovant Sciences GmbH
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Sponsor organisation address |
Viaduktstrasse 8, Basel, Switzerland, 4051
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Public contact |
Clinical Trials at Myovant, Myovant Sciences GmbH, +1 650 238 0250, clinicaltrials@myovant.com
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Scientific contact |
Clinical Trials at Myovant, Myovant Sciences GmbH , +1 650 238 0250, clinicaltrials@myovant.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Apr 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Apr 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
31 May 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
1.To determine the benefit of relugolix 40 mg once daily co-administered with 24 weeks of low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo on dysmenorrhea;
2.To determine the benefit of relugolix 40 mg once daily co-administered with 24 weeks of low-dose E2 and NETA compared with placebo on non-menstrual pelvic pain (NMPP).
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Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Sep 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 206
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Country: Number of subjects enrolled |
Sweden: 1
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Country: Number of subjects enrolled |
Czechia: 13
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Country: Number of subjects enrolled |
Italy: 24
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Country: Number of subjects enrolled |
Australia: 18
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Country: Number of subjects enrolled |
Brazil: 55
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Country: Number of subjects enrolled |
Chile: 9
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Country: Number of subjects enrolled |
Georgia: 12
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Country: Number of subjects enrolled |
New Zealand: 17
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Country: Number of subjects enrolled |
Romania: 113
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Country: Number of subjects enrolled |
United States: 155
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Worldwide total number of subjects |
623
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EEA total number of subjects |
357
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
623
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Only the participants who reported moderate, severe, or very severe dysmenorrhea during their most recent menses, and moderate, severe, or very severe NMPP during the past month on the Endometriosis-Associated Pain Severity questions were enrolled into the run-in period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
One participant in the placebo group was randomized in error and did not receive study drug. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Relugolix Plus E2/NETA (Group A) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Relugolix 40 mg co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Relugolix
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Investigational medicinal product code |
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Other name |
TAK-385, and MVT-601
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Relugolix 40-mg tablet administered orally once daily.
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Investigational medicinal product name |
Estradiol/Norethindrone acetate
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Investigational medicinal product code |
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Other name |
E2/NETA
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Capsule containing co-formulated tablet of E2 (1 mg)/NETA (0.5 mg) administered orally once daily.
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Arm title
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Relugolix Plus Delayed E2/NETA (Group B) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Relugolix monotherapy 40 mg for 12 weeks, followed by relugolix co-administered with E2 (1 mg) and NETA (0.5 mg) for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Relugolix
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Investigational medicinal product code |
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Other name |
TAK-385, and MVT-601
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Relugolix 40-mg tablet administered orally once daily.
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Investigational medicinal product name |
Estradiol/Norethindrone acetate
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Investigational medicinal product code |
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Other name |
E2/NETA
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Capsule containing co-formulated tablet of E2 (1 mg)/NETA (0.5 mg) administered orally once daily.
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Arm title
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Placebo (Group C) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Relugolix placebo co-administered with E2 and NETA placebo for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Relugolix placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, and color.
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Investigational medicinal product name |
Estradiol/Norethindrone acetate placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, and color.
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Baseline characteristics reporting groups
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Reporting group title |
Relugolix Plus E2/NETA (Group A)
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Reporting group description |
Relugolix 40 mg co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Relugolix Plus Delayed E2/NETA (Group B)
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Reporting group description |
Relugolix monotherapy 40 mg for 12 weeks, followed by relugolix co-administered with E2 (1 mg) and NETA (0.5 mg) for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (Group C)
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Reporting group description |
Relugolix placebo co-administered with E2 and NETA placebo for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Relugolix Plus E2/NETA (Group A)
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized participants who received relugolix 40 mg co-administered with estradiol (E2, 1 mg) and norethindrone acetate (NETA, 0.5 mg) for 24 weeks.
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Subject analysis set title |
Relugolix Plus Delayed E2/NETA (Group B)
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized participants who received relugolix monotherapy 40 mg for 12 weeks, followed by relugolix co-administered with E2 (1 mg) and NETA (0.5 mg) for 12 weeks.
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Subject analysis set title |
Placebo (Group C)
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants who received relugolix placebo co-administered with E2 and NETA placebo for 24 weeks.
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End points reporting groups
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Reporting group title |
Relugolix Plus E2/NETA (Group A)
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Reporting group description |
Relugolix 40 mg co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks. | ||
Reporting group title |
Relugolix Plus Delayed E2/NETA (Group B)
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Reporting group description |
Relugolix monotherapy 40 mg for 12 weeks, followed by relugolix co-administered with E2 (1 mg) and NETA (0.5 mg) for 12 weeks. | ||
Reporting group title |
Placebo (Group C)
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Reporting group description |
Relugolix placebo co-administered with E2 and NETA placebo for 24 weeks. | ||
Subject analysis set title |
Relugolix Plus E2/NETA (Group A)
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All randomized participants who received relugolix 40 mg co-administered with estradiol (E2, 1 mg) and norethindrone acetate (NETA, 0.5 mg) for 24 weeks.
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Subject analysis set title |
Relugolix Plus Delayed E2/NETA (Group B)
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All randomized participants who received relugolix monotherapy 40 mg for 12 weeks, followed by relugolix co-administered with E2 (1 mg) and NETA (0.5 mg) for 12 weeks.
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Subject analysis set title |
Placebo (Group C)
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All participants who received relugolix placebo co-administered with E2 and NETA placebo for 24 weeks.
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End point title |
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 [1] | ||||||||||||
End point description |
Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary). The criteria for a responder was based on a threshold of greater than or equal to 2.8 points and no increase in analgesic use. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
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End point type |
Primary
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End point timeframe |
Week 24
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| Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in Dysmenorrhea Responder | ||||||||||||
Statistical analysis description |
The primary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate.
|
||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [2] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
44.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
36.21 | ||||||||||||
upper limit |
53.49 | ||||||||||||
| Notes [2] - P-value was stratified by treatment, baseline average pain score, time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and geographical region (North America versus Rest of World). |
|||||||||||||
|
|||||||||||||
End point title |
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 [3] | ||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a threshold of greater than or equal to 2.1 points and no increase in analgesic use. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in NMPP Responder | ||||||||||||
Statistical analysis description |
The primary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate.
|
||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [4] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
23.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
14 | ||||||||||||
upper limit |
32.75 | ||||||||||||
| Notes [4] - P-value stratified by treatment, baseline average pain score, time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and geographical region (North America versus Rest of World). |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24 [5] | ||||||||||||
End point description |
Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an electronic tablet (eTablet) device. Participants answered the questions using the following options: never, rarely, sometimes, often, or always. The least squares (LS) means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
||||||||||||
| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in EHP-30 Pain Score | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [6] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-12.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-16.7 | ||||||||||||
upper limit |
-7.9 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.25
|
||||||||||||
| Notes [6] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since surgical endometriosis diagnosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Dysmenorrhea NRS Score At Week 24 [7] | ||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in Dysmenorrhea NRS Score | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [8] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-3.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.7 | ||||||||||||
upper limit |
-2.7 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.26
|
||||||||||||
| Notes [8] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since surgical endometriosis diagnosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In NMPP NRS Score At Week 24 [9] | ||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in NMPP NRS Score | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0012 [10] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.2 | ||||||||||||
upper limit |
-0.3 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.23
|
||||||||||||
| Notes [10] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since surgical endometriosis diagnosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 [11] | ||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Overall Pelvic Pain NRS Score | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [12] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.4 | ||||||||||||
upper limit |
-0.5 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.22
|
||||||||||||
| Notes [12] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since surgical endometriosis diagnosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Dyspareunia NRS Score At Week 24 [13] | ||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for dyspareunia recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in Dyspareunia NRS Scores | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0371 [14] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1 | ||||||||||||
upper limit |
0 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.26
|
||||||||||||
| Notes [14] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Percentage Of Participants Who Are Not Using Opioids For Endometriosis-Associated Pain At Week 24 [15] | ||||||||||||
End point description |
Assessed based on usage of protocol-specified opioids for endometriosis-associated pain recorded daily in an e-Diary. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
| Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in Opioid-free Participants | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [16] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
15.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
7.5 | ||||||||||||
upper limit |
24.2 | ||||||||||||
| Notes [16] - Nominal p-value. P-value was stratified by baseline opioid use, time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and geographic region (North America versus Rest of World). |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Analgesic Use For Endometriosis-Associated Pain Based On Mean Pill Count At Week 24 [17] | ||||||||||||
End point description |
Assessed based on usage of protocol-specified analgesic for endometriosis-associated pain recorded daily in an e-Diary. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in Analgesic Use | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.1141 [18] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.3 | ||||||||||||
upper limit |
0 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.07
|
||||||||||||
| Notes [18] - Nominal p-value. Treatment, baseline value, visit, geographic region (North America versus Rest of World), time since surgical endometriosis diagnosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||||||||
End point title |
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 [19] | ||||||||||||||||||
End point description |
Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an eTablet device. Participants answered the questions using the following options: never, rarely, sometimes, often, or always. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||||||||
| Notes [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [20] - Wk 12: n=185 Wk 24: n=170 [21] - Wk 12: n=187 Wk 24: n=162 |
|||||||||||||||||||
Statistical analysis title |
Treatment difference in EHP-30 Pain Domain (Wk 12) | ||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 12.
|
||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.0001 [22] | ||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||
Point estimate |
26.4
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
16.55 | ||||||||||||||||||
upper limit |
36.15 | ||||||||||||||||||
| Notes [22] - Nominal p-value. P-value was stratified by time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years) and geographic region (North America versus Rest of World). |
|||||||||||||||||||
Statistical analysis title |
Treatment difference in EHP-30 Pain Domain (Wk 24) | ||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 24.
|
||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0002 [23] | ||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||
Point estimate |
20.5
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
10.29 | ||||||||||||||||||
upper limit |
30.66 | ||||||||||||||||||
| Notes [23] - Nominal p-value. P-value was stratified by time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years) and geographic region (North America versus Rest of World). |
|||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Percentage Of Participants Classified As Dysmenorrhea Responder By Month [24] | ||||||||||||||||||||||||||||||
End point description |
The criteria for a responder was based on a pre-defined threshold of greater than or equal to 2.8 points and no increase in analgesic use. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Week 4 up to Week 24
|
||||||||||||||||||||||||||||||
| Notes [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Percentage Of Participants Classified As NMPP Responder By Month [25] | ||||||||||||||||||||||||||||||
End point description |
The criteria for a responder was based on a pre-defined threshold of greater than or equal to 2.1 points and no increase in analgesic use. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Week 4 up to Week 24
|
||||||||||||||||||||||||||||||
| Notes [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline In Dysmenorrhea NRS Score By Month [26] | |||||||||||||||||||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||||||||||||||
| Notes [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [27] - Wk 4: n=200 Wk 8: n=190 Wk 12: n=186 Wk 16: n=182 Wk 20: n=178 Wk 24: n=205 [28] - Wk 4: n=200 Wk 8: n=192 Wk 12: n=188 Wk 16: n=178 Wk 20: n=176 Wk 24: n=203 |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in Dysmenorrhea NRS Score (Wk 12) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 12.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [29] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-3
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-3.5 | |||||||||||||||||||||||||||||||||
upper limit |
-2.5 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.26
|
|||||||||||||||||||||||||||||||||
| Notes [29] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in Dysmenorrhea NRS Score (Wk 24) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 24.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [30] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-3.2
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-3.7 | |||||||||||||||||||||||||||||||||
upper limit |
-2.7 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.26
|
|||||||||||||||||||||||||||||||||
| Notes [30] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline In NMPP NRS Score By Month [31] | |||||||||||||||||||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||||||||||||||
| Notes [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [32] - Wk 4: n=200 Wk 8: n=190 Wk 12: n=186 Wk 16: n=182 Wk 20: n=178 Wk 24: n=205 [33] - Wk 4: n=200 Wk 8: n=192 Wk 12: n=188 Wk 16: n=178 Wk 20: n=176 Wk 24: n=203 |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Treatment difference in NMPP NRS Score (Wk 12) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 12.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0226 [34] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.5
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-0.9 | |||||||||||||||||||||||||||||||||
upper limit |
-0.1 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.21
|
|||||||||||||||||||||||||||||||||
| Notes [34] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Treatment difference in NMPP NRS Score (Wk 24) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 24.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0012 [35] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.7
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1.2 | |||||||||||||||||||||||||||||||||
upper limit |
-0.3 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.23
|
|||||||||||||||||||||||||||||||||
| Notes [35] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline In Overall Pelvic Pain NRS Score By Month [36] | |||||||||||||||||||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||||||||||||||
| Notes [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [37] - Wk 4: n=200 Wk 8: n=190 Wk 12: n=186 Wk 16: n=182 Wk 20: n=178 Wk 24: n=205 [38] - Wk 4: n=200 Wk 8: n=192 Wk 12: n=188 Wk 16: n=178 Wk 20: n=176 Wk 24: n=203 |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in Overall Pelvic Pain Score (Wk 12) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 12.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0033 [39] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.6
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1 | |||||||||||||||||||||||||||||||||
upper limit |
-0.2 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.21
|
|||||||||||||||||||||||||||||||||
| Notes [39] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in Overall Pelvic Pain Score (Wk 24) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 24.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [40] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.9
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1.4 | |||||||||||||||||||||||||||||||||
upper limit |
-0.5 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.22
|
|||||||||||||||||||||||||||||||||
| Notes [40] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
End point title |
Change From Baseline In Dyspareunia NRS Score By Month [41] | |||||||||||||||||||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||||||||||||||
| Notes [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [42] - Baseline: n=173 Wk 4: n=147 Wk 8: n=143 Wk 12: n=143 Wk 16: n=140 Wk 20: n=135 Wk 24: n=149 [43] - Baseline: n=162 Wk 4: n=139 Wk 8: n=139 Wk 12: n=134 Wk 16: n=122 Wk 20: n=125 Wk 24: n=130 |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in Dyspareunia NRS Score (Wk 12) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 12.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.2036 [44] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.3
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-0.8 | |||||||||||||||||||||||||||||||||
upper limit |
0.2 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.25
|
|||||||||||||||||||||||||||||||||
| Notes [44] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Difference in Dyspareunia NRS Score (Wk 24) | |||||||||||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate at Week 24.
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0371 [45] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.5
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1 | |||||||||||||||||||||||||||||||||
upper limit |
0 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.26
|
|||||||||||||||||||||||||||||||||
| Notes [45] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Ibuprofen Use At Week 24 [46] | ||||||||||||
End point description |
Assessed using ibuprofen pill counts for endometriosis-associated pain recorded daily in an e-Diary. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Opioid Use At Week 24 [47] | ||||||||||||
End point description |
Assessed using opioid pill counts for endometriosis-associated pain recorded daily in an e-Diary. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Dysmenorrhea Functional Impairment Score At Week 24 [48] | ||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an e-Diary. Participants were to report their pain as related to functional impairment daily in an e-Diary using the following response options: Severe (in bed all day, incapacitation), Moderate (in bed part of the day, some loss of work efficiency), Mild (some loss of work efficiency), No pain (no pain associated with menstruation during past 24 hours), or did not menstruate during the past 24 hours. Participants gave a possible score of 0 (no pain) to 4 (severe). The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Dysmenorrhea Functional Impairment | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [49] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1 | ||||||||||||
upper limit |
-0.7 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.07
|
||||||||||||
| Notes [49] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In NMPP Functional Impairment Score At Week 24 [50] | ||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an e-Diary. Participants reported their pain using the following response options: Severe (requires strong analgesics), Moderate (noticeable pelvic pain), Mild (occasional pelvic pain), or No pain (no pain during past 24 hours). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in NMPP Functional Impairment | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0111 [51] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.3 | ||||||||||||
upper limit |
0 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.07
|
||||||||||||
| Notes [51] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Dyspareunia Functional Impairment Score At Week 24 [52] | ||||||||||||
End point description |
Assessed using the participant modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an e-Diary. Participants were to report their pain during intercourse daily using the following response options: Severe (avoids intercourse because of pain), Moderate (intercourse painful to the point of causing interruption), Mild (tolerated pain), No pain (no pain during intercourse), or No intercourse (no intercourse for other reasons). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Dyspareunia Functional Impairment | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.2026 [53] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.3 | ||||||||||||
upper limit |
0.1 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.08
|
||||||||||||
| Notes [53] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In Patient Global Assessment (PGA) Score For Dysmenorrhea Symptom Severity At Week 24 [54] | ||||||||||||
End point description |
The PGA score for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in PGA For Dysmenorrhea | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [55] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-1.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.8 | ||||||||||||
upper limit |
-1.3 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.12
|
||||||||||||
| Notes [55] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Dysmenorrhea At Week 24 [56] | |||||||||||||||||||||
End point description |
The PGA score for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||
| Notes [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [57] - All categories: n=144 [58] - All categories: n=134 |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In PGA Score For NMPP Symptom Severity At Week 24 [59] | ||||||||||||
End point description |
The PGA score for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in PGA For NMPP | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0003 [60] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.6 | ||||||||||||
upper limit |
-0.2 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1
|
||||||||||||
| Notes [60] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For NMPP At Week 24 [61] | |||||||||||||||||||||
End point description |
The PGA score for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||
| Notes [61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [62] - All categories: n=145 [63] - All categories: n=134 |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In PGA Score For Pain Severity At Week 24 [64] | ||||||||||||
End point description |
The PGA score for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in PGA For Pain Severity | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0003 [65] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.5 | ||||||||||||
upper limit |
-0.2 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1
|
||||||||||||
| Notes [65] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Pain Severity At Week 24 [66] | |||||||||||||||||||||
End point description |
The PGA score for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||
| Notes [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [67] - All categories: n=168 [68] - All categories: n=158 |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In PGA Score For Function At Week 24 [69] | ||||||||||||
End point description |
The PGA score for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities. The questionnaire used a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4). The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in PGA for Function | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [70] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.8 | ||||||||||||
upper limit |
-0.5 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1
|
||||||||||||
| Notes [70] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 24 [71] | |||||||||||||||||||||
End point description |
The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities. The questionnaire used a 5-point response scale, each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4). As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
|||||||||||||||||||||
| Notes [71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [72] - All categories: n=170 [73] - All categories: n=158 |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Percentage Of Participants Who Are “Better” Or “Much Better” On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24 [74] | ||||||||||||
End point description |
The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 and Week 24
|
||||||||||||
| Notes [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in PGIC for Dysmenorrhea | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [75] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
35.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
26.11 | ||||||||||||
upper limit |
45.68 | ||||||||||||
| Notes [75] - Nominal p-value. P-value was stratified by time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years) and geographic region (North America versus Rest of World). |
|||||||||||||
|
|||||||||||||
End point title |
Percentage Of Participants Who Are “Better” Or “Much Better” On The PGIC For NMPP At Week 24 [76] | ||||||||||||
End point description |
The PGIC for NMPP is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 and Week 24
|
||||||||||||
| Notes [76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in PGIC For NMPP | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [77] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
21.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
11.87 | ||||||||||||
upper limit |
31.81 | ||||||||||||
| Notes [77] - Nominal p-value. P-value was stratified by time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years) and geographic region (North America versus Rest of World). |
|||||||||||||
|
|||||||||||||
End point title |
Percentage Of Participants Who Are “Better” Or “Much Better” On The PGIC For Dyspareunia At Week 24 [78] | ||||||||||||
End point description |
The PGIC for dyspareunia is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during sexual intercourse. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12 and Week 24
|
||||||||||||
| Notes [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in PGIC For Dyspareunia | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [79] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
24.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
13.82 | ||||||||||||
upper limit |
35.19 | ||||||||||||
| Notes [79] - Nominal p-value. P-value was stratified by time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years) and geographic region (North America versus Rest of World). |
|||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change From Baseline In The Non-Pain Of The EHP-30 Domains Score At Week 24 [80] | ||||||||||||||||||||||||
End point description |
Assessed using the non-pain domains (Control and Powerlessness, Social Support, Emotional Well-Being, and Self-Image) of the EHP-30 questionnaire. The score for each domain ranged from 0 to 100. Higher scores represent a greater (that is, more negative) impact of endometriosis. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
||||||||||||||||||||||||
| Notes [80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [81] - All categories: n=170 [82] - All categories: n=162 |
|||||||||||||||||||||||||
Statistical analysis title |
Non-Pain EHP-30 Domain (Control and Powerlessness) | ||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate for Control and Powerlessness domain.
|
||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.0001 [83] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-12.6
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-17.7 | ||||||||||||||||||||||||
upper limit |
-7.6 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.59
|
||||||||||||||||||||||||
| Notes [83] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||||||||||||||
Statistical analysis title |
Non-Pain EHP-30 Domain (Emotional Well-being) | ||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate for the Emotional Well-Being domain.
|
||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0003 [84] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-8.7
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-13.4 | ||||||||||||||||||||||||
upper limit |
-4 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.37
|
||||||||||||||||||||||||
| Notes [84] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||||||||||||||
Statistical analysis title |
Non-Pain EHP-30 Domain (Social Support) | ||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate for the Social Support domain.
|
||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0016 [85] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-8.3
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-13.4 | ||||||||||||||||||||||||
upper limit |
-3.1 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.61
|
||||||||||||||||||||||||
| Notes [85] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||||||||||||||
Statistical analysis title |
Non-Pain EHP-30 Domain (Self-Image) | ||||||||||||||||||||||||
Statistical analysis description |
The secondary efficacy analysis was the comparison of the relugolix plus E2/NETA group with the placebo group with respect to responder rate for the Self-Image domain.
|
||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.0001 [86] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-10.8
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-16.1 | ||||||||||||||||||||||||
upper limit |
-5.6 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.69
|
||||||||||||||||||||||||
| Notes [86] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In The EHP-30 Scale Total Score At Week 24 [87] | ||||||||||||
End point description |
Assessed using the total score (all 5 domains [Pain, Control and Powerlessness, Emotional Well-Being, Social Support, and Self-Image] were included) of the EHP-30 questionnaire. The total score ranged from 0 to 100. Higher scores represent a greater (that is, more negative) impact of endometriosis. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
||||||||||||
| Notes [87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in EHP-30 Scale Total Score | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [88] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-11.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-15.4 | ||||||||||||
upper limit |
-6.8 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.18
|
||||||||||||
| Notes [88] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In The EHP Work Domain Score At Week 24 [89] | ||||||||||||
End point description |
The EHP Work domain is a 5-item questionnaire that assessed the impact of pain on ability to work (for example, frequency of needing to take time off from work due to pain, inability to carry out work duties due to pain). The EHP Work domain score ranged from 0 to 100. Higher scores represent a greater (that is, more negative) impact of endometriosis on work-related activities. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 and Week 24
|
||||||||||||
| Notes [89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Treatment difference in EHP Work Domain Score | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
410
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [90] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-14.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-19.3 | ||||||||||||
upper limit |
-9.8 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.42
|
||||||||||||
| Notes [90] - Nominal p-value. Treatment, baseline value, visit, region (North America versus Rest of World), time since initial surgical diagnosis of endometriosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Categorical Change From Baseline In Quality Of Life Assessed By European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Questionnaire At Week 24 [91] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life. The EQ-5D-5L asks about limitations and problems at an instantaneous point in time ("today"). Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were each assessed on a 5-level categorical scale ranging from "no problem" to "severe problem." As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline Day 1 and Week 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [92] - All categories: n=173 [93] - All categories: n=162 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24 [94] | ||||||||||||
End point description |
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life. The EQ-5D-5L asks about limitations and problems at an instantaneous point in time ("today"). It also includes an assessment of overall health status that the participant rates on a 100-point visual analogue scale where 0 was "the worst health you could imagine" and 100 was "the best health you could imagine." As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 For Relugolix Plus Delayed E2/NETA [95] | ||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a threshold of greater than or equal to 2.8 points and no increase in analgesic use. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. As per the objective of the study, only relugolix plus delayed E2/NETA arm is presented.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 24
|
||||||||
| Notes [95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 For Relugolix Plus Delayed E2/NETA [96] | ||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a threshold of greater than or equal to 2.1 points and no increase in analgesic use. Participants rated their pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. As per the objective of the study, only relugolix plus delayed E2/NETA arm is presented.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 24
|
||||||||
| Notes [96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA [97] | ||||||||
End point description |
Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an eTablet device. Participants answered the questions using the following options: never, rarely, sometimes, often, or always. The LS means at Week 24 was compared with other treatment groups. As per the objective of the study, only relugolix plus delayed E2/NETA arm is presented.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
||||||||
| Notes [97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 For Relugolix Plus Delayed E2/NETA [98] | ||||||||||||
End point description |
Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an eTablet device. Participants answered the questions using the following options: never, rarely, sometimes, often, or always. As per the objective of the study, only relugolix plus delayed E2/NETA arm is presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 up to Week 24
|
||||||||||||
| Notes [98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
| Notes [99] - Wk 12: n=184 Wk 24: n=165 |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12 [100] | ||||||||||||
End point description |
Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points. If participants experienced bone mineral density loss of >2% from baseline, they were to undergo another bone densitometry 6 months after discontinuation of study drug. The LS means at Week 24 were compared between the relugolix plus E2/NETA and relugolix plus delayed E2/NETA groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA and are presented in this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1 and Week 12
|
||||||||||||
| Notes [100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||||||||
End point title |
Percentage Change From Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24 [101] | |||||||||||||||||||||
End point description |
Bone mineral density was assessed by DXA scan at the lumbar spine, total hip, and femoral neck (same leg for each participant) at each designated time point. The LS means at Week 24 were compared between the relugolix plus E2/NETA and relugolix plus delayed E2/NETA groups. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA and are presented in this outcome measure.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
|||||||||||||||||||||
| Notes [101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
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|
||||||||||||||||||||||
| Notes [102] - Lumbar Spine: n=168 Total Hip and Femoral Neck: n=169 [103] - All categories: n=163 |
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| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Relugolix Plus E2/NETA and Relugolix Plus Delayed E2/NETA [104] | ||||||||||||
End point description |
Vasomotor symptoms include preferred terms of hyperhidrosis, feeling hot, hot flush, night sweats and flushing. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA and are presented in this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
| Notes [104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
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|
|||||||||||||
Statistical analysis title |
Treatment difference in Vasomotor Symptoms | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Relugolix Plus Delayed E2/NETA (Group B)
|
||||||||||||
Number of subjects included in analysis |
412
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk ratio (RR) | ||||||||||||
Point estimate |
0.35
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.23 | ||||||||||||
upper limit |
0.54 | ||||||||||||
|
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End point title |
Change From Baseline In Serum Concentrations Of Luteinizing Hormone And Follicle Stimulating Hormone [105] | ||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants to determine serum concentrations of luteinizing hormone and follicle stimulating hormone using a validated method based on immuno-enzymatic assay. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
||||||||||||||||||||||||||||||
| Notes [105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
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|
|||||||||||||||||||||||||||||||
| Notes [106] - LH and FSH Baseline: n=199 LH and FSH Wk 12: n=175 LH and FSH Wk 24: n=161 [107] - LH and FSH Baseline: n=201 LH and FSH Wk 12: n=180 LH and FSH Wk 24: n=152 |
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Change From Baseline In Serum Concentrations Of Estradiol [108] | |||||||||||||||||||||
End point description |
Blood samples were collected from participants to determine serum concentrations of estradiol using a validated method based on immuno-enzymatic assay. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
|||||||||||||||||||||
| Notes [108] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Change From Baseline In Serum Concentrations Of Progesterone [109] | |||||||||||||||||||||
End point description |
Blood samples were collected from participants to determine serum concentrations of progesterone using a validated method based on immuno-enzymatic assay. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
|||||||||||||||||||||
| Notes [109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only reporting groups in which participants were randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
|
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Timeframe for reporting adverse events |
Baseline Day 1 up to Week 24
|
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Adverse event reporting additional description |
All randomized participants who received any amount of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Relugolix Plus E2/NETA (Group A)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Relugolix 40 mg co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Relugolix Plus Delayed E2/NETA (Group B)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Relugolix monotherapy 40 mg for 12 weeks, followed by relugolix co-administered with E2 (1 mg) and NETA (0.5 mg) for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (Group C)
|
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Reporting group description |
Relugolix placebo co-administered with E2 and NETA placebo for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Mar 2018 |
Amendment 1
- Included additional anchors for the co-primary end points.
- Added end points corresponding to the additional anchors for the co-primary end points.
- Supported the key secondary objective related to function.
- Allowed more time for Screening procedures to accommodate participant scheduling needs.
- Allowed for logistics related to Run-In procedures and to allow additional time, if needed, for requisite number of dysmenorrhea scores during Run-In.
- Allowed regular cycles to be demonstrated during Run-In in order to reduce the time to randomized treatment for participants who completed hormonal washout.
- Clarified the intent of Inclusion Criterion #5.
- Allowed consecutive dysmenorrhea scores from an extended Run-In Period to fulfill the minimum requirements for eligibility.
- Made the duration of required contraception to be consistent with Section 4.7 of the protocol.
- Clarified the intent of Exclusion Criterion #2 to exclude participants with multiple procedures that may cause adhesions.
- Simplified the wording of Exclusion Criterion #6 to improve clarity.
- Extended screening window for more testing to be done earlier.
- Allowed participants with recent biopsies to avoid another procedure.
- Removed the need to perform a repeat DXA when one was recently performed.
- Clarified the tests to be obtained for pharmacodynamics blood drawing.
- Removed parathyroid hormone testing since participants with abnormal calcium and phosphorus were excluded.
- Facilitated compliance with procedures previously described in other documents only.
- Added a discontinuation criterion to align with other sections of the protocol.
- Ensured that most current storage information is used.
- Provided further procedural information and allowed short-term non-study specified analgesics for intercurrent events, if needed.
- Clarified visits at which unused drug kits should be returned to sites. |
||
12 Mar 2018 |
Amendment 1
- Provided guidance for situations where P-glycoprotein inducers or inhibitors are needed while the participant is being treated with study drug.
- Better accommodation of drugs requiring a longer washout and ensured that participants' pain was being monitored and managed during washout.
- Acknowledged that procedural requirements and other scheduling constraints do not always allow for Baseline Day 1 to occur during Days 1 to 14 of menstrual cycle.
- Standardized Run-In Day 1 duration as Screening Period duration was more variable with the permitted longer window.
- Added consistency in which paper and eTablet questionnaires should be completed during each visit.
- Aligned with the intent of testing participants with low visual acuity scores (<90) at baseline.
- Updated guidance on ingestion of tea or coffee during fasting.
- Clarified procedure to be followed for participants who terminated early but did not undergo an early termination visit.
- Simplified criteria for determining when follow-up visual acuity testing is required.
- Clarified requirements for endometrial biopsies.
- Clarified requirements for electrocardiogram (ECG) procedure given that central ECG reading is not available on the same day.
- Reflected a change in the safety vendor.
- Clarified scores collected through the first dose of randomized study drug to be used for the baseline period.
- The term "ITT" was updated to "modified ITT" to better reflect that planned analysis was not changed.
- Clarified that safety reporting will be in accordance with United States (US) and non-US health authority requirements.
- Clarified that protocol modifications will be in accordance with US and non-US health authority requirements.
- Provided greater specificity and to further detail prescribing procedures. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
