SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain

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

The purpose of this study is to evaluate the long-term efficacy and safety of relugolix 40 milligram (mg) once daily co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) for up to 104 weeks on endometriosis-associated pain in participants who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3101 or MVT-601-3102).

Study Overview

• Status: Completed
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Relugolix; Drug: Estradiol/norethindrone acetate

Detailed Description

This study is an international phase 3 open-label, single-arm, long-term efficacy and safety extension study that will enroll eligible participants who have completed their participation in one of the phase 3 randomized, double-blind, placebo-controlled parent studies, MVT-601-3101 (SPIRIT 1 - NCT03204318) or MVT-601-3102 (SPIRIT 2 - NCT03204331). All participants will receive relugolix 40 mg orally once daily co-administered with low-dose E2 (1.0 mg) and NETA (0.5 mg) for 80 weeks.

Approximately 800 women with endometriosis-associated pain will be enrolled, after having completed a 24-week treatment period in one of the parent studies. The objectives of the study are to evaluate long-term efficacy and safety through up to 104 weeks of treatment (including treatment during the parent study) of relugolix co-administered with low-dose E2/NETA.

Baseline procedures for this extension study will be performed on the same day as the Week 24 Visit of the parent study. This visit, referred to as the "Week 24/Baseline Visit, will be defined as the date of completion of the last Week 24 procedure in the parent study. Participants will have received their last dose of study drug in the parent study on the day prior to the Week 24/Baseline Visit and will receive their first dose of study drug for this extension study in the clinic after the participant is determined to be eligible for this extension study and has provided informed consent to participate. The administration of the first dose of study drug for MVT-601-3103 will define enrollment into this study. Study participants will then take the open-label study treatment orally, once daily for 80 weeks.

• Study Type: Interventional
• Enrollment (Actual): 802
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, X5000JHQ
    • Cordoba
  • Buenos Aires
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, C1128AAF
      • Ciudad de Buenos Aires
    • San Isidro, Buenos Aires, Argentina, B1642CKL
      • San Isidro
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000PRB
      • Rosario
• Australia
  • NS
    • Wollongong, NS, Australia, 2522
      • Wollongong
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Sydney
  • Queensland
    • Taringa, Queensland, Australia, 4068
      • Taringa
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Adelaide
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Nedlands
• Belgium
  • Brussels, Belgium, 1070
    • Brussels
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Leuven
  • Hainaut
    • La Louvière, Hainaut, Belgium, 7100
      • La Louvière
  • Oost-vlaanderen
    • Gent, Oost-vlaanderen, Belgium, 9000
      • Gent
• Brazil
  • Sao Paulo, Brazil, 01317-000
    • São Paulo
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080
      • Passo Fundo
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90430-001
      • Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90510-040
      • Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Porto Alegre
  • Sao Paulo
    • Porto Alegre, Sao Paulo, Brazil, 90035-903
      • Porto Alegre
    • São Bernardo do Campo, Sao Paulo, Brazil, 09715-090
      • São Bernardo do Campo
    • São Paulo, Sao Paulo, Brazil, 04023-062
      • São Paulo
    • São Paulo, Sao Paulo, Brazil, 04266-010
      • São Paulo
    • São Paulo, Sao Paulo, Brazil, 04708-001
      • São Paulo
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Blagoevgrad
  • Pleven, Bulgaria, 5809
    • Pleven
  • Stara Zagora, Bulgaria, 6003
    • Stara Zagora
  • Varna, Bulgaria, 9002
    • Varna
  • Sofiya
    • Sofia, Sofiya, Bulgaria, 1233
      • Sofia
    • Sofia, Sofiya, Bulgaria, 1431
      • Sofia
    • Sofia, Sofiya, Bulgaria, 1504
      • Sofia
    • Sofia, Sofiya, Bulgaria, 1336
      • Sofia
• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4N 6V7
      • Red Deer
  • Ontario
    • Waterloo, Ontario, Canada, N2J1C4
      • Waterloo
  • Quebec
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Victoriaville
• Chile
  • Santiago, Chile, 7510186
    • Santiago
  • Santiago, Chile, 8880465
    • Santiago
  • Santiago, Chile, 8320143
    • Santiago
• Czechia
  • Olomouc, Czechia, 772 00
    • Olomouc
  • Praha 8 - Libeň, Czechia, 180 81
    • Praha 8 - Libeň
  • České Budějovice, Czechia, 370 01
    • České Budějovice
  • Jihocesky
    • Vodňany, Jihocesky, Czechia, 389 01
      • Vodňany
  • Jihocesky Kraj
    • Písek, Jihocesky Kraj, Czechia, 397 01
      • Pisek
  • Jihormoravsky Kraj
    • Tábor, Jihormoravsky Kraj, Czechia, 390 03
      • Tábor
  • Kralovehradecky
    • Náchod, Kralovehradecky, Czechia, 547 01
      • Náchod
  • Praha
    • Praha 10, Praha, Czechia, 100 34
      • Praha 10
    • Praha 2, Praha, Czechia, 128 08
      • Praha 2
• Finland
  • Oulu, Finland, 90100
    • Oulu
  • Eastern Finland
    • Kuopio, Eastern Finland, Finland, 70100
      • Kuopio
  • Southern Finland
    • Helsinki, Southern Finland, Finland, 00260
      • Helsinki
• Georgia
  • Tbilisi, Georgia, 0159
    • Tbilisi
• Hungary
  • Bacs-kiskun
    • Kecskemét, Bacs-kiskun, Hungary, 6000
      • Kecskemét
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • Pécs
  • Bekes
    • Békéscsaba, Bekes, Hungary, 5600
      • Békéscsaba
    • Gyula, Bekes, Hungary, 5700
      • Gyula
  • Csongrad
    • Szeged, Csongrad, Hungary, 6725
      • Szeged
  • Hajdu-bihar
    • Debrecen, Hajdu-bihar, Hungary, 4024
      • Debrecen
    • Debrecen, Hajdu-bihar, Hungary, 4025
      • Debrecen
    • Debrecen, Hajdu-bihar, Hungary, 4032
      • Debrecen
  • Szabolcs-szatmar-bereg
    • Nyíregyháza, Szabolcs-szatmar-bereg, Hungary, 4400
      • Nyíregyháza
• Italy
  • Catanzaro, Italy, 88100
    • Catanzaro
  • Napoli, Italy, 80131
    • Napoli
  • Pavia, Italy, 27100
    • Pavia
  • Roma, Italy, 00168
    • Roma
  • Cagliari
    • Monserrato, Cagliari, Italy, 9042
      • Monserrato
• New Zealand
  • Christchurch, New Zealand, 8013
    • Christchurch
  • Auckland
    • Remuera, Auckland, New Zealand, 1050
      • Remuera
  • Manawatu-wanganui
    • Palmerston North, Manawatu-wanganui, New Zealand, 4442
      • Palmerston North
• Poland
  • Lodzkie
    • Łódź, Lodzkie, Poland, 90-602
      • Łodź
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-064
      • Lublin
    • Lublin, Lubelskie, Poland, 20-632
      • Lublin
    • Lublin, Lubelskie, Poland, 20-880
      • Lublin
    • Lublin, Lubelskie, Poland, 20-093
      • Lublin
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-066
      • Warszawa
    • Warszawa, Mazowieckie, Poland, 02-929
      • Warszawa
    • Warszawa, Mazowieckie, Poland, 02-201
      • Warszawa
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-224
      • Białystok
  • Slaskie
    • Katowice, Slaskie, Poland, 40-081
      • Katowice
    • Katowice, Slaskie, Poland, 40-301
      • Katowice
  • Wielkopolskie
    • Skórzewo, Wielkopolskie, Poland, 60-185
      • Skórzewo
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 71-434
      • Szczecin
• Portugal
  • Coimbra, Portugal, 3000-075
    • Coimbra
  • Covilhã, Portugal, 6200-251
    • Covilhã
  • Porto, Portugal, 4099-001
    • Porto
  • Lisboa
    • Almada, Lisboa, Portugal, 2805-267
      • Almada
• Romania
  • Brasov, Romania, 500091
    • Brasov
  • Bucuresti, Romania, 012071
    • Bucuresti
  • Bucuresti, Romania, 022441
    • Bucuresti
  • Bucuresti, Romania, 024091
    • Bucuresti
  • București, Romania, 20475
    • Bucuresti
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Port Elizabeth
  • Gauteng
    • Centurion, Gauteng, South Africa, 0157
      • Centurion
    • Roodepoort, Gauteng, South Africa, 1724
      • Roodepoort
  • Kwazulu-natal
    • Durban, Kwazulu-natal, South Africa, 4126
      • Durban
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7405
      • Cape Town
• Spain
  • Madrid, Spain, 28041
    • Madrid
  • Valencia, Spain, 46010
    • Valencia
• Ukraine
  • Chernivtsi, Ukraine, 58001
    • Chernivtsi
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk
  • Kharkiv, Ukraine, 61052
    • Kharkiv
  • Kiev, Ukraine, 3148
    • Kiev
  • Kiev, Ukraine, 4112
    • Kiev
  • Kyiv, Ukraine, 04053
    • Kyiv
  • Zaporizhzhya, Ukraine, 69065
    • Zaporizhzhya
  • Zaporizhzhya, Ukraine, 69068
    • Zaporizhzhya
  • Zaporizhzhya, Ukraine, 69071
    • Zaporizhzhya
  • Zaporizhzhya, Ukraine, 69063
    • Zaporizhzhya
  • Kiev
    • Kyiv, Kiev, Ukraine, 1034
      • Kyiv
  • Kiev City
    • Kyiv, Kiev City, Ukraine, 2232
      • Kyiv
    • Kyiv, Kiev City, Ukraine, 4050
      • Kyiv
• United States
  • Alabama
    • Andalusia, Alabama, United States, 36420
      • Andalusia
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Scottsdale
    • Tucson, Arizona, United States, 85704
      • Tucson
    • Tucson, Arizona, United States, 85712
      • Tuscon
  • California
    • Canoga Park, California, United States, 91303
      • Canoga Park
    • Los Angeles, California, United States, 70433
      • Los Angeles
    • San Diego, California, United States, 92111
      • San Diego
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • Greenwood Village
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Washington
  • Florida
    • Aventura, Florida, United States, 33180
      • Aventura
    • Fort Myers, Florida, United States, 33912
      • Fort Myers
    • Hialeah, Florida, United States, 33012
      • Hialeah
    • Hialeah, Florida, United States, 33016
      • Hialeah
    • Margate, Florida, United States, 33063
      • Margate
    • Miami, Florida, United States, 33126
      • Miami
    • Miami, Florida, United States, 33155
      • Miami
    • Sarasota, Florida, United States, 34239
      • Sarasota
    • Tampa, Florida, United States, 33606
      • Tampa
  • Georgia
    • Atlanta, Georgia, United States, 30363
      • Atlanta
    • Atlanta, Georgia, United States, 30312
      • Atlanta
    • Augusta, Georgia, United States, 30909
      • Augusta
    • Norcross, Georgia, United States, 30093
      • Norcross
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Idaho Falls
  • Illinois
    • Oakbrook Terrace, Illinois, United States, 60523
      • Oakbrook
    • Park Ridge, Illinois, United States, 60068
      • Park Ridge
  • Kansas
    • Shawnee Mission, Kansas, United States, 66218
      • Shawnee
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Marrero
  • Maryland
    • Towson, Maryland, United States, 21204
      • Towson
  • Michigan
    • Saginaw, Michigan, United States, 48602
      • Saginaw
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Jefferson City
    • Saint Louis, Missouri, United States, 63141
      • St. Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Durham
    • New Bern, North Carolina, United States, 28562
      • New Bern
    • Winston-Salem, North Carolina, United States, 27103
      • Winston Salem
  • Ohio
    • Akron, Ohio, United States, 44313
      • Akron
    • Columbus, Ohio, United States, 43235
      • Columbus
    • Englewood, Ohio, United States, 45322
      • Englewood
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Hershey
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Columbia
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga
    • Memphis, Tennessee, United States, 38120
      • Memphis
  • Texas
    • Beaumont, Texas, United States, 77702
      • Beaumont
    • Corpus Christi, Texas, United States, 78412
      • Corpus Christi
    • Dallas, Texas, United States, 75231
      • Dallas
    • Fort Worth, Texas, United States, 76104
      • Fort Worth
    • Houston, Texas, United States, 77030
      • Houston
    • Houston, Texas, United States, 77054
      • Houston
    • Irving, Texas, United States, 75062
      • Irving
    • San Antonio, Texas, United States, 78258
      • San Antonio
    • Sugar Land, Texas, United States, 77479
      • Sugar Land
    • Webster, Texas, United States, 77598
      • Webster
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Salt Lake City
    • Salt Lake City, Utah, United States, 84107
      • Salt Lake City
    • Salt Lake City, Utah, United States, 84102
      • Salt Lake City
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Norfolk
    • Richmond, Virginia, United States, 23235
      • Richmond
    • Virginia Beach, Virginia, United States, 23502
      • Virginia Beach
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 47 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Completed 24 weeks of study drug treatment and study participation in either parent study, MVT-601-3101 or MVT-601-3102.
2. Is not expected to undergo gynecological surgery or other surgical procedures for treatment of endometriosis (including ablation, shaving, or excision) during the study, including during the Follow-Up Period, and the participant does not desire such treatment during this time frame.
3. Has agreed to continue to use only study-specified analgesic medications during the study and is not known to be intolerant to these.

Key Exclusion Criteria:

1. Has had a surgical procedure for treatment for endometriosis at any time during the parent study (MVT-601-3101 or MVT-601-3102).
2. Has any chronic pain or frequently recurring pain condition, other than endometriosis, that is treated with opioids or requires analgesics for ≥ 7 days per month.
3. Has a Z-score < -2.0 or has a ≥ 7% decrease in bone mineral density from the parent study Baseline at lumbar spine, total hip, or femoral neck based on the parent study Week 24 DXA assessment of bone mineral density.

4. Has any contraindication to treatment with low-dose E2 and NETA, including:

   1. Known, suspected, or history of breast cancer;
   2. Known or suspected estrogen-dependent neoplasia;
   3. Active deep vein thrombosis or pulmonary embolism, or history of these conditions prior to the Week 24/Baseline visit;
   4. History of or active arterial thromboembolic disease, including stroke and myocardial infarction;
   5. Known anaphylactic reaction or angioedema or hypersensitivity to E2 or NETA;
   6. Known protein C, protein S, or antithrombin deficiency, or other known thrombophilia disorders, including Factor V Leiden;
   7. Migraine with aura;
   8. History of porphyria.

5. Had any of the following clinical laboratory abnormalities at the parent study Week 20 visit or, if available, any subsequent visit in one of the parent studies (MVT-601-3101 or MVT-601-3102):

   1. Alanine aminotransferase or aspartate aminotransferase > 2.0 times the upper limit of normal (ULN); or
   2. Bilirubin (total bilirubin) > 1.5 x ULN (or > 2.0 x ULN if secondary to Gilbert syndrome or pattern consistent with Gilbert syndrome).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relugolix plus E2/NETA; Relugolix co-administered with E2/NETA for 80 weeks.	Drug: Relugolix; Relugolix 40-mg tablet administered orally once daily; Other Names: TAK-385; MVT-601; Drug: Estradiol/norethindrone acetate; Capsule containing co-formulated tablet of E2 (1.0 mg) and NETA (0.5 mg) administered orally once daily; Other Names: E2/NETA; low-dose hormonal add-back

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 52	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.	Week 52
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 52	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.	Week 52
Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 104	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.	Week 104
Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 104	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.	Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Endometriosis Health Profile (EHP)-30 Pain Domain Scores At Week 104	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.	Week 104
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	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.	Week 52
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	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.	Week 104
Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean Dysmenorrhea NRS Score At Week 104	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.	Week 104
Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean NMPP NRS Score At Week 104	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.	Week 104
Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean Overall Pelvic Pain NRS Score At Week 104	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.	Week 104
Percentage Of Participants Not Using Opioids For Endometriosis-associated Pain At Week 104	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.	Week 104
Percentage Of Participants Not Using Analgesics For Endometriosis-associated Pain At Week 104	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.	Week 104
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia NRS Scores At Week 104	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.	Week 104
Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In The Mean Dyspareunia Functional Impairment At Week 104	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.	Week 104
Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In Severity Scores On The Patient Global Assessment (PGA) For Overall Pelvic Pain At Week 104	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.	Week 104
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 52	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).	Week 52
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Overall Pelvic Pain At Week 104	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).	Week 104
Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In Function Impairment On The PGA For Function At Week 104	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.	Week 104
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 52	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).	Week 52
Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA Score For Function At Week 104	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).	Week 104
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In Each Of The Non-Pain EHP-30 Domains At Week 104	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.	Week 104
Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 52	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.	Week 52
Change From The Pivotal Phase 3 Study Baseline In Dysmenorrhea Functional Impairment Score At Week 104	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.	Week 104
Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 52	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.	Week 52
Change From Pivotal Phase 3 Study Baseline In NMPP Functional Impairment Score At Week 104	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.	Week 104
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52	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.	Week 52
Percent Change From The Pivotal Phase 3 Study Baseline In BMD At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 104	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.	Week 104
Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 52	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.	Week 52
Change From Pivotal Phase 3 Study Baseline In Predose Serum Concentrations Of Estradiol At Week 104	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.	Week 104

Collaborators and Investigators

• Sponsor: Myovant Sciences GmbH
• Investigators: Study Director: Myovant Medical Monitor, Myovant Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2018
• Primary Completion (Actual): December 16, 2021
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: August 29, 2018
• First Submitted That Met QC Criteria: August 29, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Dysmenorrhea; Endometriosis; Dyspareunia; Pelvic Pain
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometriosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Androgen Antagonists; Estradiol; Norethindrone; Norethindrone Acetate; Relugolix
• Other Study ID Numbers: MVT-601-3103; 2017-004066-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No