Clinical Trial Results:
SPIRIT EXTENSION: An International Phase 3 Open-Label, Single-Arm, Safety and Efficacy Extension Study to Evaluate Relugolix Co-Administered with Low-Dose Estradiol and Norethindrone Acetate in Women with Endometriosis-Associated Pain
Summary
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EudraCT number |
2017-004066-10 |
Trial protocol |
GB ES HU BE FI SE PL CZ BG PT IT RO |
Global end of trial date |
23 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Aug 2023
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First version publication date |
20 Aug 2023
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Other versions |
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-601-3103
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03654274 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND: 076642 | ||
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 |
VP of Clinical Operations, Myovant Sciences GmbH, +1 (650)238 0250, SPIRIT@myovant.com
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Scientific contact |
VP of Clinical Operations, Myovant Sciences GmbH, +1 (650)238 0250, SPIRIT@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 |
21 Jul 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Dec 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Jan 2023
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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 |
To evaluate long-term efficacy of relugolix 40 mg once daily co administered with low-dose estradiol and norethindrone acetate for up to 52 and 104 weeks, among patients who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3101 or MVT 601-3102), on endometriosis-associated pain.
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Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) E6 (R2) (Guideline for Good Clinical Practice [GCP]), applicable patient privacy requirements, and the ethical principles outlined in the Declaration of Helsinki 2013. Additionally, the study was conducted in accordance with the United States (US) Code of Federal Regulations, the European Union Clinical Trials Directive, and applicable local/regional regulations and guidelines regarding the conduct of clinical studies.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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: 297
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Country: Number of subjects enrolled |
Portugal: 7
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Country: Number of subjects enrolled |
Romania: 31
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
Belgium: 8
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Country: Number of subjects enrolled |
Bulgaria: 29
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Country: Number of subjects enrolled |
Czechia: 28
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Country: Number of subjects enrolled |
Finland: 5
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Country: Number of subjects enrolled |
Hungary: 24
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Country: Number of subjects enrolled |
Italy: 17
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Country: Number of subjects enrolled |
United States: 147
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Country: Number of subjects enrolled |
Argentina: 34
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Country: Number of subjects enrolled |
Australia: 11
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Country: Number of subjects enrolled |
Brazil: 41
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Country: Number of subjects enrolled |
Canada: 6
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Country: Number of subjects enrolled |
Chile: 5
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Country: Number of subjects enrolled |
Georgia: 7
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Country: Number of subjects enrolled |
New Zealand: 8
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Country: Number of subjects enrolled |
South Africa: 32
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Country: Number of subjects enrolled |
Ukraine: 63
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Worldwide total number of subjects |
802
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EEA total number of subjects |
448
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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) |
802
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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 |
All participants who completed their participation in one of the pivotal studies (MVT-601-3101 or MVT-601-3102) were eligible to enroll in this study. Due to data integrity concerns at 1 US site, 3 patients (1 relugolix + E2/NETA; 2 Placebo) were excluded from efficacy and safety analyses, but included in demographic and disposition tables. | ||||||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The study results were presented by pivotal study treatment but all the participants only received relugolix plus Estradiol (E2)/Norethindrone Acetate (NETA). Three participants (1 in the relugolix plus E2/NETA group; 2 in the placebo group) were excluded due to GCP noncompliance and no data is reported for these participants. | ||||||||||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||||||
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 once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||
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 |
Estradiol/Norethindrone acetate
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Investigational medicinal product code |
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Other name |
E2/NETA, low-dose hormonal add-back
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Capsule containing co-formulated tablet of E2 (1 mg)/NETA (0.5 mg) administered orally once daily.
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Arm title
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Relugolix Plus Delayed E2/NETA (Group B) | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily coadministered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||
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 |
Estradiol/Norethindrone acetate
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Investigational medicinal product code |
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Other name |
E2/NETA, low-dose hormonal add-back
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Capsule containing co-formulated tablet of E2 (1 mg)/NETA (0.5 mg) administered orally once daily.
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Arm title
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Placebo (Group C) | ||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||
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 |
Estradiol/Norethindrone acetate
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Investigational medicinal product code |
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Other name |
E2/NETA, low-dose hormonal add-back
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Capsule containing co-formulated tablet of E2 (1 mg)/NETA (0.5 mg) administered orally once daily.
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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 once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Relugolix Plus Delayed E2/NETA (Group B)
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Reporting group description |
Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily coadministered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (Group C)
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Reporting group description |
Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||
Reporting group title |
Relugolix Plus Delayed E2/NETA (Group B)
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Reporting group description |
Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily coadministered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||
Reporting group title |
Placebo (Group C)
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Reporting group description |
Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. |
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End point title |
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 52 [1] | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 52 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
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End point type |
Primary
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End point timeframe |
Week 52
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The responder rate and two-sided 95% CI will be presented by the pivotal phase 3 study treatment group. No treatment comparisons will be performed for this extension study. |
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No statistical analyses for this end point |
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End point title |
Percentage Of Participants Who Meet The Nonmenstrual Pelvic Pain Responder Criteria At Week 52 [2] | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 52 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
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End point type |
Primary
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End point timeframe |
Week 52
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The responder rate and two-sided 95% CI will be presented by the pivotal phase 3 study treatment group. No treatment comparisons will be performed for this extension study. |
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No statistical analyses for this end point |
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End point title |
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 104 [3] | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 104 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
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End point type |
Primary
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End point timeframe |
Week 104
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: . |
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No statistical analyses for this end point |
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End point title |
Percentage Of Participants Who Meet The Nonmenstrual Pelvic Pain Responder Criteria At Week 104 [4] | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 104 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.
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End point type |
Primary
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End point timeframe |
Week 104
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The responder rate and two-sided 95% CI will be presented by the pivotal phase 3 study treatment group. No treatment comparisons will be performed for this extension study. |
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No statistical analyses for this end point |
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End point title |
Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 52 | ||||||||||||||||
End point description |
Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an
electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain. The least squares (LS) mean was presented by pivotal study treatment group and by visit.
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End point type |
Secondary
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End point timeframe |
Week 52
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No statistical analyses for this end point |
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End point title |
Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 104 | ||||||||||||||||
End point description |
Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an
electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain. The least squares (LS) mean was presented by pivotal study treatment group and by visit.
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End point type |
Secondary
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End point timeframe |
Week 104
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No statistical analyses for this end point |
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End point title |
Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain Scores From The Pivotal Phase 3 Study Baseline At Week 52 | ||||||||||||||||
End point description |
Assessed using the Pain Domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an
electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
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 Scores From The Pivotal Phase 3 Study Baseline At Week 104 | ||||||||||||||||
End point description |
Assessed using the Pain Domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an
electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always)
with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 52 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their
pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 104 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their
pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
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 52 | ||||||||||||||||
End point description |
The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participant’s 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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 52 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their
pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 104 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their
pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 52 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for overall pain recorded daily in an electronic diary. Participants rated their overall pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 104 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for overall pain recorded daily in an electronic diary. Participants rated their overall pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage Of Participants Not Using Opioids For Endometriosis-associated Pain At Week 104 | ||||||||||||||||
End point description |
Assessed based on usage of study-specified opioids for endometriosis-associated pain recorded daily in an electronic diary. Participants received protocol-specified opioids for treatment of endometriosis-associated pain as needed for pain but not prophylactically.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage Of Participants Not Using Analgesics For Endometriosis-associated Pain At Week 104 | ||||||||||||||||
End point description |
Assessed based on usage of study-specified analgesics for endometriosis-associated pain recorded daily in an
electronic diary. Participants received protocol-specified analgesics for treatment of endometriosis-associated pain as needed for pain but not prophylactically.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 52 | ||||||||||||||||
End point description |
The PGIC for NMPP is a 1-item questionnaire designed to assess participant’s impression of change in the severity
of pain when they are not menstruating. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 52 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants were to report whether they had vaginal sexual intercourse and rated their level of pelvic pain during intercourse on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 104 | ||||||||||||||||
End point description |
Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants were to report whether they had vaginal sexual intercourse and rated their level of pelvic pain during intercourse on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 52 | ||||||||||||||||
End point description |
The PGIC for dyspareunia is a 1-item questionnaire designed to assess participant’s impression of change in the
severity of their 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.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 52 | ||||||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an electronic diary. Participants were to report their pain during intercourse daily using the following response options: Severe (avoids intercourse because of pain), Moderate (intercourse painful to the point of causing interruption), Mild (tolerated pain), No pain (no pain during intercourse), or No intercourse (no intercourse for other reasons). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 104 | ||||||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an electronic diary. Participants were to report their pain during intercourse daily using the following response options: Severe (avoids intercourse because of pain), Moderate (intercourse painful to the point of causing interruption), Mild (tolerated pain), No pain (no pain during intercourse), or No intercourse (no intercourse for other reasons). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 52 | ||||||||||||||||
End point description |
The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant’s impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 104 | ||||||||||||||||
End point description |
The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant’s impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 52 | ||||||||||||||||||||||||||||
End point description |
The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant's impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4).
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 104 | ||||||||||||||||||||||||||||
End point description |
The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant's impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4).
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 52 | ||||||||||||||||
End point description |
The PGA for functional impairment is a 1-item questionnaire designed to assess participant’s impression of how their pain affected their usual activities. The participants responded to the question: “How much were your daily activities limited by endometriosis over the last 4 weeks?” using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 104 | ||||||||||||||||
End point description |
The PGA for functional impairment is a 1-item questionnaire designed to assess participant’s impression of how their pain affected their usual activities. The participants responded to the question: “How much were your daily activities limited by endometriosis over the last 4 weeks?” using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 52 | ||||||||||||||||||||||||||||
End point description |
The PGA for functional impairment is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities. The participants responded to the question: "How much were your daily activities limited by endometriosis over the last 4 weeks?" using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4).
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 104 | ||||||||||||||||||||||||||||
End point description |
The PGA for functional impairment is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities. The participants responded to the question: "How much were your daily activities limited by endometriosis over the last 4 weeks?" using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4).
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52 | ||||||||||||||||||||||||||||||||
End point description |
Assessed using the following non-pain domains of the EHP-30 questionnaire: Control and Powerlessness (questions 12 through 17), Emotional Well-Being (questions 18 through 23), Social Support (questions 24 through 27), and Self-Image (questions 28 through 30). The score for each domain ranged from 0 to 100. Higher scores represent a greater impact of endometriosis. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104 | ||||||||||||||||||||||||||||||||
End point description |
Assessed using the following non-pain domains of the EHP-30 questionnaire: Control and Powerlessness (questions 12 through 17), Emotional Well-Being (questions 18 through 23), Social Support (questions 24 through 27), and Self-Image (questions 28 through 30). The score for each domain ranged from 0 to 100. Higher scores represent a greater impact of endometriosis. The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 52 | ||||||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an electronic diary. Participants were to report their pain as related to functional impairment daily in an electronic diary using the following response options: Severe (in bed all day, incapacitation), Moderate (in bed part of the day, some loss of work efficiency), Mild (some loss of work efficiency), No pain (no pain associated with menstruation during past 24 hours), or did not menstruate during the past 24 hours. Participants gave a possible score of 0 (no pain) to 4 (did not menstruate). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 104 | ||||||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an electronic diary. Participants were to report their pain as related to functional impairment daily in an electronic diary using the following response options: Severe (in bed all day, incapacitation), Moderate (in bed part of the day, some loss of work efficiency), Mild (some loss of work efficiency), No pain (no pain associated with menstruation during past 24 hours), or did not menstruate during the past 24 hours. Participants gave a possible score of 0 (no pain) to 4 (did not menstruate). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 52 | ||||||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an electronic diary. Participants reported their pain daily in an electronic diary using the following response options: Severe (requires strong analgesics), Moderate (noticeable pelvic pain), Mild (occasional pelvic pain), or No pain (no pain during past 24 hours). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 104 | ||||||||||||||||
End point description |
Assessed using the participant-modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an electronic diary. Participants reported their pain daily in an electronic diary using the following response options: Severe (requires strong analgesics), Moderate (noticeable pelvic pain), Mild (occasional pelvic pain), or No pain (no pain during past 24 hours). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 | ||||||||||||||||||||||||||||
End point description |
Assessed by dual-energy X-ray absorptiometry (DXA) scan at lumbar spine, total hip, and femoral neck (same leg for each participant) at each designated time point. All participants who completed treatment or terminated from the study early were required to return for a 6-month post-treatment follow-up (PTFU) and a 12-month PTFU DXA scan (except if participant was beyond 14 months from last day on treatment). Participants were also to have clinical laboratory evaluations (vitamin D, thyroid stimulating hormone, parathyroid hormone, creatinine, calcium, and phosphorous) at the 6-month and 12-month PTFU only if the PTFU DXA scans showed a bone loss of ≥3% at the lumbar spine and/or total hip compared with the parent study baseline.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Notes [5] - Note that the number of participants analyzed for Lumbar Spine was n=204. [6] - Note that the number of participants analyzed for Femoral Neck was n=231 and for Total hip was n=231 |
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||
End point title |
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 104 | ||||||||||||||||||||||||||||
End point description |
Assessed by dual-energy X-ray absorptiometry (DXA) scan at lumbar spine, total hip, and femoral neck (same leg for each participant) at each designated time point. All participants who completed treatment or terminated from the study early were required to return for a 6-month post-treatment follow-up (PTFU) and a 12-month PTFU DXA scan (except if participant was beyond 14 months from last day on treatment). Participants were also to have clinical laboratory evaluations (vitamin D, thyroid stimulating hormone, parathyroid hormone, creatinine, calcium, and phosphorous) at the 6-month and 12-month PTFU only if the PTFU DXA scans showed a bone loss of ≥3% at the lumbar spine and/or total hip compared with the parent study baseline.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Notes [7] - Note that the number of participants analyzed for Femoral Neck was and for Total hip was n=170 |
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 52 | ||||||||||||||||
End point description |
Blood samples were collected from participants for estradiol measurements at each specified timepoints. Estradiol concentrations were measured using an immuno-enzymatic assay based on a commercially available kit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 52
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 104 | ||||||||||||||||
End point description |
Blood samples were collected from participants for estradiol measurements at each specified timepoints. Estradiol concentrations were measured using an immuno-enzymatic assay based on a commercially available kit.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Week 104
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Week 24/Baseline up to Week 104
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Extension Safety Population: all enrolled participants who received any amount of open-label study drug in MVT-601-3103. Study results are reported by pivotal study treatment, but all participants only received relugolix Plus E2/NETA.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Relugolix Plus E2/NETA (Group A)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Relugolix 40 mg once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Relugolix Plus Delayed E2/NETA (Group B)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Relugolix 40 mg monotherapy (once daily) for 12 weeks, followed by oral relugolix 40 mg once daily coadministered with E2 (1mg) and NETA (0.5 mg) for 12 weeks in the pivotal study and Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (Group C)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Relugolix placebo co-administered with E2/NETA placebo for up to 24 weeks in the pivotal study followed by Relugolix 40 mg once daily co-administered with E2/NETA for 80 weeks in this extension study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Mar 2018 |
Amendment 1: to align the protocol with changes made to the parent protocols MVT-601-3101/3102.
- Secondary endpoint responder analyses for EHP-30 pain domain added at Week 52.
- For endpoint of proportion of responders at Week 52/EOT based on EHP-30 Pain Domain scores, a responder is defined using the same within-patient score change threshold determined from the parent studies.
- Updated exclusion criteria 1 to simplify wording to improve clarity.
- Clarified that “throughout the study” also included the 30 days following the last dose of study drug.
- Clarified that early termination visit DXA is not required if the early termination visit occurred prior to the Week 32 visit or within 4 weeks after completion of the Week 36 DXA.
- Procedural details for IVRS/IWRS and e-Diary deactivation added.
- Referred reader to study drug labeling for details of study drug storage to ensure most current storage information is used.
- New section (“Rescue Analgesic Medications”) added to provide further procedural information and to allow short-term non-study specified analgesics for intercurrent events, if needed.
- Clarified the visits at which unused drug kits should be returned to sites.
- Clarified procedure to be followed for patients who terminated early but did not undergo an ET visit.
- Changed safety vendor.
- “ITT” was updated to “modified ITT” to better reflect that planned analysis.
- Lot numbers to be maintained during drug accountability to reflect the fact that study drug kits contain lot numbers.
- Clarified that safety reporting and protocol modifications will be in accordance with US and non-US health authority requirements.
- Updated to specify Tier 1 and Tier 2 study-specified analgesic examples and prescribing procedures. |
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11 Dec 2018 |
Amendment 2: Extended study to 104 weeks of treatment, inclusive of the 24 weeks in parent study.
- Updated primary and secondary objectives to reflect study extension and plan to conduct analyses on data through Week 52 and 104, resulting in a CSR for each analysis.
- Included endometrial biopsy at Week 52 and optional endometrial biopsy at Week 104.
- Clarified open-label nature of study.
- Updated timing elements to reflect extension to 104 total weeks of treatment.
- Clarified that first dose of study drug could be initiated up to 10 days after completion of parent study.
- Clarified when DXA scans would be conducted and follow-up rules for DXA results.
- Clarified visual acuity criteria.
- Updated Statistical Methods to reflect extension of treatment and provide a description of analyses to be conducted on Week 104 data.
- Updated Schedule of Activities to reflect extension of treatment.
- Add telephone contact at Weeks 57, 71, 85,and 98.
- Clarified what would be reviewed during telephone contact.
- Clarified which physical examinations would include a breast examination.
- Clarified timing of eDiary entries.
- Reference documents (Lab and Study Reference Manuals) updated to Investigator Site File.
- Clarified pregnancy test procedures for patients whose parent study Week 24 visit was different than baseline visit for this study.
- Updated pregnancy testing language so that testing would coincide with patient visits from Week 52 to Week 104.
- Clarified cannabinoids are prohibited during study.
- Clarified where concomitant medications should be recorded.
- Indicated that last scheduled ECG is planned for Week 52 visit.
- Added language regarding assessment of bone densitometry and follow-up procedures.
- Clarified safety assessments that could be performed at unscheduled visits.
- Removed PK plasma samples included in error.
- Clarified timepoints to be used in efficacy analyses.
- Clarified which baseline visit is referenced in text. |
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01 Jul 2020 |
Amendment 3: included a mammogram at Week 52 or Week 104/Early Termination for women ≥ 40 years old.
- Included additional objectives and endpoints to evaluate pelvic pain and analgesic use.
- Added mammogram for patients over 40 years age.
- Clarified timing of mammograms.
- Added details to correspond with the addition of mammograms.
- Clarified follow-up procedures for bone mineral density loss.
- Clarified procedures for when a patient is lost to follow-up.
- Added ECG at Week 104/Early Termination visit.
- Added bone densitometry follow-up.
- Added clinical laboratory tests during follow-up period since they may be included as part of bone densitometry follow-up.
- Added endometrial biopsy follow up.
- Added clarifying footnote to Schedule of Activities for status of menstruation recovery during safety follow-up.
- Clarified endometrial biopsy procedures and timing.
- Included removal criteria for findings resulting from mammogram.
- Added language for increased counselling on contraception.
- Included COVID-19 guidance.
- Removed copper from IUD description to reduce confusion with inclusion criterion 6c.
- Clarified investigator role in communicating to sponsor when a patient refuses the endometrial biopsy.
- Clarified reporting instructions for adverse events.
- Clarified timing of overdose reporting requirements.
- Added clarification about the documentation of pregnancy.
- Included added assessments of mammograms for patients over 40 and endometrial biopsy to list of safety assessments. |
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25 Aug 2020 |
Amendment 3.1: included a mammogram at Week 52 or Week 104/Early Termination (ET) for women ≥ 40 years old and revised threshold for post-treatment follow-up.
- Included additional objectives and endpoints to evaluate pelvic pain and analgesic use.
- Added mammogram for patients ≥ 40 years age details to correspond with this addition.
- Clarified timing of mammograms.
- Clarified follow-up procedures for bone mineral density (BMD) loss. Lowered threshold for post-treatment follow-up. Specified follow up procedure for BMD loss at Week 104 visit.
- Clarified procedures for when a patient is lost to follow-up.
- Corrected “modified ITT” population to “Extension Study” population.
- Added ECG at Week 104/ET visit.
- Added bone densitometry follow-up.
- Added clinical laboratory tests during follow-up period since they may be included as part of bone densitometry follow-up.
- Added endometrial biopsy follow up.
- Added clarifying footnote to Schedule of Activities for status of menstruation recovery during safety follow-up.
- Clarified endometrial biopsy procedures and timing. Added an endometrial biopsy at ET visit.
- Included removal criteria for findings resulting from mammogram.
- Added language for increased counselling on contraception.
- Included COVID-19 guidance.
- Removed copper from IUD description to reduce confusion with inclusion criterion 6c.
- Clarified procedure for laboratory assessment during study and post database lock.
- Clarified investigator role in communicating to sponsor when a patient refuses the endometrial biopsy.
- Clarified reporting instructions for adverse events.
- Clarified timing of overdose reporting requirements.
- Added clarification about the documentation of pregnancy.
- Included added assessments of mammograms for patients ≥ 40 and endometrial biopsy to list of safety assessments.
- Added guidance on site closure and pending follow up procedures
- Clarified analysis populations for efficacy/safety data. |
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01 Jul 2021 |
Amendment 4: added 6-month and 12-month post-treatment follow-up dual-energy x-ray absorptiometry (DXA) scans for all patients.
- added 6-month and 12-month post-treatment follow-up DXA scans
- Added 6-month and 12-month post-treatment follow-up assessments and labs.
- Extended eDiary entry collection to 30-day follow-up visit.
- Added new safety objective.
- Added new section for collection of fracture events based on recent FDA recommendations.
- Clarified patients should only take study-specified analgesics approved in their country.
- Defined fragility fracture and request for them to be reported in the posttreatment period. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |