Clinical Trial Results:
SPIRIT 1: 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 |
2017-001588-19 |
Trial protocol |
CZ ES HU BE PL BG PT FI |
Global end of trial date |
09 Jun 2020
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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-601-3101
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03204318 | ||
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 |
09 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Jun 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jun 2020
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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 and norethindrone acetate compared with placebo on dysmenorrhea;
2.To determine the benefit of relugolix 40 mg once daily co-administered with 24 weeks of low-dose estradiol and norethindrone acetate 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 on 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 |
01 Jul 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: 165
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Country: Number of subjects enrolled |
Portugal: 10
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
Belgium: 12
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Country: Number of subjects enrolled |
Bulgaria: 50
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Country: Number of subjects enrolled |
Czechia: 36
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Country: Number of subjects enrolled |
Finland: 6
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Country: Number of subjects enrolled |
Hungary: 41
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Country: Number of subjects enrolled |
Canada: 11
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Country: Number of subjects enrolled |
United States: 110
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Country: Number of subjects enrolled |
Argentina: 38
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Country: Number of subjects enrolled |
South Africa: 45
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Country: Number of subjects enrolled |
Ukraine: 112
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Worldwide total number of subjects |
638
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EEA total number of subjects |
322
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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) |
638
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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 |
Participants with endometriosis-associated pain 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 (EAPS) questionnaire. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Three participants, 2 participants in the relugolix + delayed estradiol (E2)/norethindrone acetate (NETA) group and 1 participant in the placebo group were randomized but did not receive study drug since they were randomized in error as they had not met all eligibility requirements. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall (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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
All participants, investigators, and sponsor staff or representatives involved in the conduct of the study were blinded to treatment assignment.
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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/NETA (1 mg/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, 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 |
E2/NETA
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Investigational medicinal product code |
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Other name |
E2/NETA
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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 |
Capsule containing co-formulated tablet of E2 (1.0 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 40 mg co-administered with E2/NETA (1 mg/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, 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 |
E2/NETA
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Investigational medicinal product code |
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Other name |
E2/NETA
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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 |
Capsule containing co-formulated tablet of E2 (1.0 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/NETA placebo for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
E2/NETA 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, color, and odor.
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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, color, and odor.
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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/NETA (1 mg/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 40 mg co-administered with E2/NETA (1 mg/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/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 |
Relugolix 40 mg co-administered with E2/NETA (1 mg/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 |
Relugolix monotherapy 40 mg for 12 weeks, followed by relugolix 40 mg co-administered with E2/NETA (1 mg/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 |
Relugolix placebo co-administered with E2/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/NETA (1 mg/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 40 mg co-administered with E2/NETA (1 mg/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/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 |
Relugolix 40 mg co-administered with E2/NETA (1 mg/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 |
Relugolix monotherapy 40 mg for 12 weeks, followed by relugolix 40 mg co-administered with E2/NETA (1 mg/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 |
Relugolix placebo co-administered with E2/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 an 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. Higher NRS score means worse condition (0 = no pain to 10 = 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 |
Baseline Day 1 up to Week 24
|
||||||||||||
| 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [2] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
47.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
39.27 | ||||||||||||
upper limit |
56.01 | ||||||||||||
| 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. Higher NRS score means worse condition (0 = no pain to 10 = 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 |
Baseline Day 1 up to 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [4] | ||||||||||||
Method |
Regression, Logistic | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
18.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
9.52 | ||||||||||||
upper limit |
28.21 | ||||||||||||
| Notes [4] - P-value stratified by treatment, baseline average pain score, time since surgical endometriosis diagnosis (<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. Participants completed the EHP-30 questionnaire on an eTablet device and 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [6] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-15.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-19.7 | ||||||||||||
upper limit |
-10.5 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.33
|
||||||||||||
| 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. Higher NRS score means worse condition (0 = no pain to 10 = 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [8] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-3.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.8 | ||||||||||||
upper limit |
-2.8 | ||||||||||||
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. Higher NRS score means worse condition (0 = no pain to 10 = 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0002 [10] | ||||||||||||
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 |
-0.4 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.24
|
||||||||||||
| 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. Higher NRS score means worse condition (0 = no pain to 10 = 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [12] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-1.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.6 | ||||||||||||
upper limit |
-0.7 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.24
|
||||||||||||
| 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 |
Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 [13] | ||||||||||||
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 |
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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0005 [14] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
9.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
2 | ||||||||||||
upper limit |
16.8 | ||||||||||||
| Notes [14] - 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 Dyspareunia NRS Scores At Week 24 [15] | ||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for dyspareunia recorded daily in an e-Diary. Higher NRS score means worse condition (0 = no pain to 10 = 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 [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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0149 [16] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.3 | ||||||||||||
upper limit |
-0.1 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.29
|
||||||||||||
| Notes [16] - 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 |
Percentage of Participants Who Are Not Using Analgesics For Endometriosis-associated Pain At Week 24 [17] | ||||||||||||
End point description |
Assessed based on usage of protocol-specified analgesic use 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 [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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Analgesic-free Participants | ||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [18] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
25.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
16.4 | ||||||||||||
upper limit |
34.6 | ||||||||||||
| Notes [18] - Nominal p-value. P-value was stratified by baseline analgesic 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 |
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. Participants completed the EHP-30 questionnaire on an eTablet device and 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 |
Week 12 and 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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||||||||
|
|||||||||||||||||||
| Notes [20] - Week 12: n=187 Week 24: n=173 [21] - Week 12: n=186 Week 24: n=165 |
|||||||||||||||||||
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 |
424
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.0001 [22] | ||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||
Point estimate |
27.6
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
17.87 | ||||||||||||||||||
upper limit |
37.32 | ||||||||||||||||||
| 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 |
424
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.0001 [23] | ||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||
Point estimate |
27.8
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
17.9 | ||||||||||||||||||
upper limit |
37.73 | ||||||||||||||||||
| 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 Rate 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 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 Rate 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 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. Higher NRS score means worse condition (0 = no pain to 10 = 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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [27] - Wk 4: n=202 Wk 8: n=196 Wk 12: n=193 Wk 16: n=187 Wk 20: n=184 Wk 24: n=211 [28] - Wk 4: n=205 Wk 8: n=198 Wk 12: n=189 Wk 16: n=180 Wk 20: n=178 |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [29] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-3.3
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-3.8 | |||||||||||||||||||||||||||||||||
upper limit |
-2.7 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.27
|
|||||||||||||||||||||||||||||||||
| Notes [29] - 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. |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [30] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-3.3
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-3.8 | |||||||||||||||||||||||||||||||||
upper limit |
-2.8 | |||||||||||||||||||||||||||||||||
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 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 By Month [31] | |||||||||||||||||||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Higher NRS score means worse condition (0 = no pain to 10 = 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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [32] - Wk 4: n=202 Wk 8: n=196 Wk 12: n=193 Wk 16: n=187 Wk 20: n=184 Wk 24: n=211 [33] - Wk 4: n=205 Wk 8: n=198 Wk 12: n=189 Wk 16: n=180 Wk 20: n=178 |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0041 [34] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.6
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1.1 | |||||||||||||||||||||||||||||||||
upper limit |
-0.2 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.22
|
|||||||||||||||||||||||||||||||||
| Notes [34] - 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. |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0002 [35] | |||||||||||||||||||||||||||||||||
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 |
-0.4 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.24
|
|||||||||||||||||||||||||||||||||
| Notes [35] - 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 By Month [36] | |||||||||||||||||||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Higher NRS score means worse condition (0 = no pain to 10 = 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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [37] - Wk 4: n=202 Wk 8: n=196 Wk 12: n=193 Wk 16: n=187 Wk 20: n=184 Wk 24: n=211 [38] - Wk 4: n=205 Wk 8: n=198 Wk 12: n=189 Wk 16: n=180 Wk 20: n=178 |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0001 [39] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.8
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1.3 | |||||||||||||||||||||||||||||||||
upper limit |
-0.4 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.22
|
|||||||||||||||||||||||||||||||||
| Notes [39] - 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. |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.0001 [40] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-1.1
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1.6 | |||||||||||||||||||||||||||||||||
upper limit |
-0.7 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.24
|
|||||||||||||||||||||||||||||||||
| Notes [40] - 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 By Month [41] | |||||||||||||||||||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. Higher NRS score means worse condition (0 = no pain to 10 = 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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
| Notes [42] - Baseline: n=174 Wk 4: n=149 Wk 8: n=142 Wk 12: n=136 Wk 16: n=137 Wk 20: n=136 Wk 24: n=148 [43] - Baseline: n=165 Wk 4: n=140 Wk 8: n=140 Wk 12: n=126 Wk 16: n=120 Wk 20: n=123 Wk 24: n=138 |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.4374 [44] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.2
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-0.8 | |||||||||||||||||||||||||||||||||
upper limit |
0.3 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.27
|
|||||||||||||||||||||||||||||||||
| Notes [44] - 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. |
||||||||||||||||||||||||||||||||||
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 |
424
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
= 0.0149 [45] | |||||||||||||||||||||||||||||||||
Method |
Mixed models analysis | |||||||||||||||||||||||||||||||||
Parameter type |
Treatment difference | |||||||||||||||||||||||||||||||||
Point estimate |
-0.7
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-1.3 | |||||||||||||||||||||||||||||||||
upper limit |
-0.1 | |||||||||||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
|||||||||||||||||||||||||||||||||
Dispersion value |
0.29
|
|||||||||||||||||||||||||||||||||
| Notes [45] - 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 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 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 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 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 The Mean Dysmenorrhea Functional Impairment 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 using the following response options: Severe (in bed all day, incapacitation), Moderate (in bed part of 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) for this scale. 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [49] | ||||||||||||
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 |
-0.6 | ||||||||||||
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 surgical endometriosis diagnosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In The Mean NMPP Functional Impairment 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) for this scale. 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0006 [51] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.4 | ||||||||||||
upper limit |
-0.1 | ||||||||||||
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 surgical endometriosis diagnosis (<5 years versus ≥5 years), and treatment-by-visit interaction included as fixed effects. |
|||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In The Mean Dyspareunia Functional Impairment 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 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) for this scale. 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0352 [53] | ||||||||||||
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 |
0.08
|
||||||||||||
| Notes [53] - 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 Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At Week 24 [54] | ||||||||||||
End point description |
The PGA 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), and 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [55] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-1.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.1 | ||||||||||||
upper limit |
-1.7 | ||||||||||||
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 surgical endometriosis diagnosis (<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 For Dysmenorrhea At Week 24 [56] | |||||||||||||||||||||
End point description |
The PGA 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), and 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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [57] - All categories: n=152 [58] - All categories: n=145 |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Change From Baseline In PGA For NMPP Symptom Severity At Week 24 [59] | ||||||||||||
End point description |
The PGA 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), and 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [60] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.7 | ||||||||||||
upper limit |
-0.3 | ||||||||||||
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 surgical endometriosis diagnosis (<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 For NMPP At Week 24 [61] | |||||||||||||||||||||
End point description |
The PGA 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), and 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 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 PGA For Pain Severity At Week 24 [62] | ||||||||||||
End point description |
The PGA 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), and 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 [62] - 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [63] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.7 | ||||||||||||
upper limit |
-0.3 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1
|
||||||||||||
| Notes [63] - 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 |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24 [64] | |||||||||||||||||||||
End point description |
The PGA 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), and 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 [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 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 PGA For Function At Week 24 [65] | ||||||||||||
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), and 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 [65] - 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [66] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.8 | ||||||||||||
upper limit |
-0.4 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.1
|
||||||||||||
| Notes [66] - 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 |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24 [67] | |||||||||||||||||||||
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), and 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 [67] - 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 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 Are “Better” Or “Much Better” On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24 [68] | ||||||||||||
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 [68] - 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [69] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
35.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
26.07 | ||||||||||||
upper limit |
45.46 | ||||||||||||
| Notes [69] - 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 [70] | ||||||||||||
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 [70] - 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [71] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
28.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
18.24 | ||||||||||||
upper limit |
37.99 | ||||||||||||
| Notes [71] - 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 [72] | ||||||||||||
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 [72] - 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [73] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
23.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
12.99 | ||||||||||||
upper limit |
34.08 | ||||||||||||
| Notes [73] - 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 At Week 24 [74] | ||||||||||||||||||||||||
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 [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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
|||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [75] - All categories: n=173 [76] - All categories: n=165 |
|||||||||||||||||||||||||
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 |
424
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.0001 [77] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-17
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-22.3 | ||||||||||||||||||||||||
upper limit |
-11.7 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.7
|
||||||||||||||||||||||||
| Notes [77] - 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. |
|||||||||||||||||||||||||
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 Emotional Well-being domain.
|
||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0004 [78] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-8.8
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-13.6 | ||||||||||||||||||||||||
upper limit |
-3.9 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.45
|
||||||||||||||||||||||||
| Notes [78] - 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. |
|||||||||||||||||||||||||
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 Social Support domain.
|
||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0001 [79] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-10.5
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-15.8 | ||||||||||||||||||||||||
upper limit |
-5.2 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.71
|
||||||||||||||||||||||||
| Notes [79] - 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. |
|||||||||||||||||||||||||
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 Self-image domain.
|
||||||||||||||||||||||||
Comparison groups |
Relugolix Plus E2/NETA (Group A) v Placebo (Group C)
|
||||||||||||||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.0001 [80] | ||||||||||||||||||||||||
Method |
Mixed models analysis | ||||||||||||||||||||||||
Parameter type |
Treatment difference | ||||||||||||||||||||||||
Point estimate |
-11.2
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-16.7 | ||||||||||||||||||||||||
upper limit |
-5.7 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.81
|
||||||||||||||||||||||||
| Notes [80] - 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 The EHP-30 Scale Total Score At Week 24 [81] | ||||||||||||
End point description |
Assessed using the total score of the EHP-30 questionnaire. The 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 [81] - 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [82] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-13.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-17.7 | ||||||||||||
upper limit |
-8.8 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.26
|
||||||||||||
| Notes [82] - 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 The EHP Work Domain Score At Week 24 [83] | ||||||||||||
End point description |
The EHP Work domain is a 5-item questionnaire that assesses impact of pain on ability to work. The questionnaire assessed the effects of endometriosis on 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 [83] - 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 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 |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [84] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-13.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-18.4 | ||||||||||||
upper limit |
-8.8 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
2.44
|
||||||||||||
| Notes [84] - 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 |
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 [85] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life. 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 are each assessed on a five-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 [85] - 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 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 To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24 [86] | ||||||||||||
End point description |
The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life. 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 and Week 24
|
||||||||||||
| Notes [86] - 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 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 [87] | ||||||||
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. Higher NRS score means worse condition (0 = no pain to 10 = 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 |
Baseline Day 1 up to 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 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 [88] | ||||||||
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. Higher NRS score means worse condition (0 = no pain to 10 = 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 |
Baseline Day 1 up to Week 24
|
||||||||
| Notes [88] - 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 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 [89] | ||||||||
End point description |
Assessed using the Pain Domain of the EHP-30 questionnaire. Participants completed the EHP-30 questionnaire on an eTablet device and answered the questions using the following options: never, rarely, sometimes, often, or always. The LS means at Week 24 were compared between the relugolix plus E2/NETA and placebo 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 [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 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 [90] | ||||||||||||
End point description |
Assessed using the pain domain of the EHP-30 questionnaire. Participants completed the EHP-30 questionnaire on an eTablet device and 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, Week 12, and Week 24
|
||||||||||||
| Notes [90] - 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 randomized to Relugolix Plus Delayed E2/NETA (Group B) were analyzed in this end point. |
|||||||||||||
|
|||||||||||||
| Notes [91] - Week 12: n=190 Week 24: n=178 |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage Change From Baseline In BMD At The Lumbar Spine (L1-L4) At Week 12 [92] | ||||||||||||
End point description |
Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points. If participants experienced BMD 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 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. Therefore, only relugolix plus E2/NETA and relugolix plus delayed E2/NETA are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline Day 1, Week 12, and Week 24
|
||||||||||||
| Notes [92] - 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 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 BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24 [93] | |||||||||||||||||||||
End point description |
BMD was assessed by DXA scan at the lumbar spine, total hip, and femoral neck (same leg for each participant) at each designated time points. 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 relugolix plus delayed E2/NETA. Therefore, only relugolix plus E2/NETA and relugolix plus delayed E2/NETA are presented.
|
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End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline Day 1, week 12, and Week 24
|
|||||||||||||||||||||
| Notes [93] - 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 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 [94] - All categories: n=164 [95] - All categories: n=161 |
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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 [96] | ||||||||||||
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. Therefore, only relugolix plus E2/NETA and relugolix plus delayed E2/NETA are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
| 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 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 |
423
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Parameter type |
Risk ratio (RR) | ||||||||||||
Point estimate |
0.25
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
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lower limit |
0.15 | ||||||||||||
upper limit |
0.4 | ||||||||||||
|
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End point title |
Change From Baseline In Serum Concentrations Of Luteinizing Hormone and Follicle Stimulating Hormone [97] | ||||||||||||||||||||||||||||||
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.
|
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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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
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|
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| Notes [98] - LH and FSH Baseline: n=209 LH and FSH Wk 12: n=185 LH and FSH Wk 24: n=168 [99] - LH Baseline: n=209 LH Wk 12: n=182 LH and FSH Wk 24: n=165 FSH Baseline: n=207 FSH Wk 12: n=181 |
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Pre-dose Relugolix Plasma Concentrations At Week 4 [100] | ||||||||||||
End point description |
Blood samples were collected from participants to determine plasma concentrations of relugolix using a validated bioanalytical methodology based on high performance liquid chromatography coupled to tandem mass spectrometry. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA. Therefore, only relugolix plus E2/NETA and relugolix plus delayed E2/NETA arms are presented.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 4
|
||||||||||||
| 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 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 |
Endometrial Biopsy At Week 24 [101] | ||||||||||||||||||||||||||||||||||||
End point description |
Primary diagnosis of endometrial biopsy assessment by pathologist. Endometrial biopsy is not required at the early termination visit if the last dose of the study drug taken was during week 6 or earlier. As per the objective of the study, the pre-specified secondary efficacy analyses compared relugolix plus E2/NETA with relugolix plus delayed E2/NETA. Therefore, only relugolix plus E2/NETA and relugolix plus delayed E2/NETA arms are presented.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline Day 1 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 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 |
Change From Baseline In Serum Concentrations Of Estradiol [102] | |||||||||||||||||||||
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 [102] - 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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [103] - Baseline: n=209 Wk 12: n=185 Wk 24: n=168 [104] - Baseline: n=207 Wk 12: n=179 Wk 24: n=164 |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Change From Baseline In Serum Concentrations Of Progesterone [105] | |||||||||||||||||||||
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 [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 randomized to Relugolix Plus E2/NETA (Group A) and Placebo (Group C) were analyzed in this end point. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [106] - Baseline: n=209 Week 12: n=185 Week 24: n=168 [107] - Baseline: n=209 Week 12: n=182 Week 24: n=165 |
||||||||||||||||||||||
| 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
|
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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/NETA (1 mg/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 40 mg co-administered with E2/NETA (1 mg/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/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 |
- Corrected list of locations.
- Included additional anchors for the co-primary endpoints.
- Added endpoints corresponding to the additional anchors for the co-primary endpoints.
- Supported the key secondary objective related to function.
- Allowed more time for Screening procedures and accommodated participant scheduling needs.
- Allowed for logistics related to Run-In procedures and allowed additional time, if needed, for requisite number of dysmenorrhea scores during Run-In.
- Allowed demonstration of regular cycles 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 determination.
- Made duration of required contraception 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 wording for Exclusion Criterion #6 to improve clarity.
- Allowed longer screening window since it permits more testing to be done earlier.
- Removed the need to perform a repeat DXA when one was recently performed.
- Clarified tests to obtain for pharmacokinetics vs. pharmacodynamics blood drawing.
- Removed parathyroid hormone testing because participants with abnormal calcium and phosphorus were excluded.
- Facilitated compliance with procedures previously described in other documents.
- Added discontinuation criterion to align with other sections of the protocol.
- Ensured 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 |
- Provided guidance for situations where P-gp inducers or inhibitors are needed while the participant is being treated with study drug.
- Accommodated drugs requiring 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 1-14 of menstrual cycle.
- Standardized duration (10 weeks of Run-In Day 1) as Screening Period duration will now be more variable with the longer window permitted.
- Added consistency in which paper and electronic tablet questionnaires should be completed during each visit.
- Acknowledged limited value of baseline testing for study objectives.
- 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 ET visit.
- Simplified criteria for determining when follow-up visual acuity testing is required.
- Clarified requirements for endometrial biopsies procedure.
- Clarified requirements for ECG procedure given that central ECG reading is not available on the same day.
- Reflected a change in the safety vendor.
- Clarified that scores collected through the first dose of randomized study drug will be used for the baseline period.
- The term “ITT” was updated to “modified ITT” to better reflect that the planned analysis was not changed.
- Clarified that safety reporting and protocol modifications will be in accordance with US and non-US health authority requirements.
- Provided greater specificity and further detail procedures for Tier 1 and Tier 2 study-specific analgesics. |
||
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 | |||
