SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain

NCT03204318 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: MVT-601-31012017-001588-19
• Study Type: interventional
• Target: 638
• Locations: 13 countries
• Sites: 123

Brief Summary

The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.

Conditions

Endometriosis Related Pain

Keywords

Endometriosis; Pain; Dysmenorrhea

Outcome Measures

Primary Outcomes (2)

• Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT)

  Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.

  Week 24 or EOT

• Percentage Of Participants Who Meet The Non-Menstrual Pelvic Pain (NMPP) Responder Criteria At Week 24 Or EOT

  Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.

  Week 24 or EOT

Secondary Outcomes (45)

• Change From Baseline In The Endometriosis Health Profile (EHP)-30 Pain Score At Week 24

  Baseline, Week 24

• Change From Baseline In Dysmenorrhea NRS Score At Week 24 Or EOT

  Baseline, Week 24 or EOT

• Change From Baseline In NMPP NRS Score At Week 24 Or EOT

  Baseline, Week 24 or EOT

• Change From Baseline In Overall Pelvic Pain NRS Score At Week 24 Or EOT

  Baseline, Week 24 or EOT

• Percentage Of Participants Who Are Not Using Opioids For Endometriosis-associated Pain At Week 24 Or EOT

  Week 24 or EOT

Study Arms (3)

Relugolix plus E2/NETA (Group A)

EXPERIMENTAL

Relugolix co-administered with E2/NETA for 24 weeks.

Drug: Relugolix; Drug: Estradiol/norethindrone acetate

Relugolix plus Delayed E2/NETA (Group B)

EXPERIMENTAL

Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.

Drug: Relugolix; Drug: Estradiol/norethindrone acetate; Drug: Estradiol/norethindrone acetate placebo

Placebo (Group C)

PLACEBO COMPARATOR

Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.

Drug: Estradiol/norethindrone acetate placebo; Drug: Relugolix placebo

Interventions

Relugolix DRUG

Relugolix 40-mg tablet administered orally once daily.

Also known as: TAK-385, MVT-601

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Estradiol/norethindrone acetate DRUG

Capsule containing co-formulated tablet of E2 (1.0 mg)/NETA (0.5 mg) administered orally once daily.

Also known as: E2/NETA

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Estradiol/norethindrone acetate placebo DRUG

E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor.

Placebo (Group C); Relugolix plus Delayed E2/NETA (Group B)

Relugolix placebo DRUG

Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.

Placebo (Group C)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of the informed consent form.
• Has agreed to use only study-specified analgesic medications during the study and is not known to be intolerant to these.
• Has a diagnosis of endometriosis and has had, within 10 years prior to signing the informed consent form, surgical or direct visualization and/or histopathologic confirmation of endometriosis, for example, during a laparoscopy or laparotomy.
• During the Run-In Period (35 to 70 days prior to treatment period) has a dysmenorrhea NRS score ≥ 4.0 on at least 2 days and
• Mean NMPP NRS score ≥ 2.5, or
• Mean NMPP NRS score ≥ 1.25 and NMPP NRS score ≥ 5.0 on ≥ 4 days.

You may not qualify if:

• Has a history of chronic pelvic pain that is not caused by endometriosis.
• 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.
• Has had surgical procedures for treatment of endometriosis within the 3 months prior to the Screening visit.
• Has a history of or currently has osteoporosis or other metabolic bone disease.
• Has a clinically significant gynecologic condition, other than endometriosis, identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.

Sponsors & Collaborators

• Myovant Sciences GmbH: lead

Study Sites (123)

Dothan

Dothan, Alabama, 36303, United States

Location

Mesa

Mesa, Arizona, 85209, United States

Location

Scottsdale

Scottsdale, Arizona, 85251, United States

Location

Tucson

Tucson, Arizona, 85704, United States

Location

Tucson

Tucson, Arizona, 85712, United States

Location

Canoga Park

Canoga Park, California, 91303, United States

Location

Long Beach

Long Beach, California, 90806, United States

Location

San Diego

San Diego, California, 92111, United States

Location

Greenwood Village

Greenwood Village, Colorado, 80111, United States

Location

Fort Myers

Fort Myers, Florida, 33912, United States

Location

Loxahatchee

Loxahatchee Groves, Florida, 33470, United States

Location

Miami

Miami, Florida, 33126, United States

Location

Miami

Miami, Florida, 33155, United States

Location

Orlando

Orlando, Florida, 32808, United States

Location

Oviedo

Oviedo, Florida, 32765, United States

Location

Plantation

Plantation, Florida, 33324, United States

Location

Sarasota

Sarasota, Florida, 34239, United States

Location

Atlanta

Atlanta, Georgia, 30363, United States

Location

Augusta

Augusta, Georgia, 30909, United States

Location

Norcross

Norcross, Georgia, 30093, United States

Location

Idaho Falls

Idaho Falls, Idaho, 83404, United States

Location

Oakbrook

Oak Brook, Illinois, 60523, United States

Location

Shawnee

Shawnee Mission, Kansas, 66218, United States

Location

New Orleans

New Orleans, Louisiana, 70115, United States

Location

Jefferson City

Jefferson City, Missouri, 65109, United States

Location

Las Vegas

Las Vegas, Nevada, 89113, United States

Location

Port Jefferson

Port Jefferson, New York, 11777, United States

Location

Durham

Durham, North Carolina, 27713, United States

Location

Raleigh

Raleigh, North Carolina, 27612, United States

Location

Winston Salem

Winston-Salem, North Carolina, 27103, United States

Location

Englewood

Englewood, Ohio, 45322, United States

Location

Hershey

Hershey, Pennsylvania, 17033, United States

Location

Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Memphis

Memphis, Tennessee, 38120, United States

Location

Murfreesboro

Murfreesboro, Tennessee, 37130, United States

Location

Austin

Austin, Texas, 78705, United States

Location

Houston

Houston, Texas, 77030, United States

Location

Webster

Webster, Texas, 77598, United States

Location

Salt Lake City

Salt Lake City, Utah, 84107, United States

Location

Salt Lake City

Salt Lake City, Utah, 84124, United States

Location

Norfolk

Norfolk, Virginia, 23507, United States

Location

Richmond

Richmond, Virginia, 23235, United States

Location

Seattle

Seattle, Washington, 98105, United States

Location

Ciudad de Buenos Aires

Ciudad de Buenos Aires, Buenos Aires, C1128AAF, Argentina

Location

San Isidro

San Isidro, Buenos Aires, B1642CKL, Argentina

Location

Rosario

Rosario, Santa Fe Province, S2000PRB, Argentina

Location

Córdoba

Córdoba, X5000JHQ, Argentina

Location

Leuven

Leuven, Flemish Brabant, 3000, Belgium

Location

La Louvière

La Louvière, Hainaut, 7100, Belgium

Location

Gent

Ghent, Oost-vlaanderen, 9000, Belgium

Location

Brussels

Brussels, 1070, Belgium

Location

Sofia

Sofia, Sofia, 1233, Bulgaria

Location

Sofia

Sofia, Sofia, 1431, Bulgaria

Location

Sofia

Sofia, Sofia, 1504, Bulgaria

Location

Blagoevgrad

Blagoevgrad, 2700, Bulgaria

Location

Pleven

Pleven, 5809, Bulgaria

Location

Sofia

Sofia, 1336, Bulgaria

Location

Sofia

Sofia, 1606, Bulgaria

Location

Stara Zagora

Stara Zagora, 6003, Bulgaria

Location

Varna

Varna, 9005, Bulgaria

Location

Red Deer

Red Deer, Alberta, T4N 6V7, Canada

Location

Waterloo

Waterloo, Ontario, N2J1C4, Canada

Location

Victoriaville

Victoriaville, Quebec, G6P 6P6, Canada

Location

Praha 10

Prague, Prague, 100 34, Czechia

Location

Nachod

Náchod, 54701, Czechia

Location

Olomouc

Olomouc, 772 00, Czechia

Location

Praha 8 - Libeň

Praha 8 - Libeň, 180 81, Czechia

Location

Vodnany

Vodňany, 389 01, Czechia

Location

Vysoké Mýto

Vysoké Mýto, 566 01, Czechia

Location

Kuopio

Kuopio, Eastern Finland, FI-70110, Finland

Location

Helsinki

Helsinki, Southern Finland, 00260, Finland

Location

Oulu

Oulu, 90100, Finland

Location

Pécs

Pécs, Baranya, 7624, Hungary

Location

Békéscsaba

Békéscsaba, Bekes County, 5600, Hungary

Location

Gyula

Gyula, Bekes County, 5700, Hungary

Location

Kecskemét

Kecskemét, Bács-Kiskun county, 6000, Hungary

Location

Szeged

Szeged, Csongrád megye, 6725, Hungary

Location

Debrecen

Debrecen, Hajdú-Bihar, 4024, Hungary

Location

Debrecen

Debrecen, Hajdú-Bihar, 4025, Hungary

Location

Debrecen

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Nyíregyháza

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

Budapest

Budapest, 1027, Hungary

Location

Budapest

Budapest, 1062, Hungary

Location

Budapest

Budapest, 1135, Hungary

Location

Poznań

Poznan, Greater Poland Voivodeship, 60-535, Poland

Location

Skórzewo

Skórzewo, Greater Poland Voivodeship, 601-85, Poland

Location

Kraków

Krakow, Lesser Poland Voivodeship, 31-121, Poland

Location

Lublin

Lublin, Lublin Voivodeship, 20-064, Poland

Location

Lublin

Lublin, Lublin Voivodeship, 20-632, Poland

Location

Lublin

Lublin, Lublin Voivodeship, 20-880, Poland

Location

Warszawa

Warsaw, Masovian Voivodeship, 02-066, Poland

Location

Warszawa

Warsaw, Masovian Voivodeship, 02-929, Poland

Location

Białystok

Bialystok, Podlaskie Voivodeship, 15-224, Poland

Location

Katowice

Katowice, Silesian Voivodeship, 02-066, Poland

Location

Katowice

Katowice, Silesian Voivodeship, 40-081, Poland

Location

Szczecin

Szczecin, West Pomeranian Voivodeship, 71-434, Poland

Location

Lódz

Lódz, Łódź Voivodeship, 90-602, Poland

Location

Almada

Almada, Lisbon District, 2805-267, Portugal

Location

Coimbra

Coimbra, 3000-075, Portugal

Location

Covilhã

Covilha, 6200-251, Portugal

Location

Lisbon

Lisbon, 1069-089, Portugal

Location

Porto

Porto, 4099-001, Portugal

Location

Port Elizabeth

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Centurion

Centurion, Gauteng, 0157, South Africa

Location

Roodepoort

Roodepoort, Gauteng, 1724, South Africa

Location

Durban

Durban, KwaZulu-Natal, 4001, South Africa

Location

Cape Town

Cape Town, Western Cape, 7405, South Africa

Location

Madrid

Madrid, 28041, Spain

Location

Valencia

Valencia, 46010, Spain

Location

Kyiv

Kyiv, Kiev City, 02232, Ukraine

Location

Kyiv

Kyiv, Kiev City, 04050, Ukraine

Location

Kyiv

Kyiv, Kyiv City, 01034, Ukraine

Location

Chernivtsi

Chernivtsi, 58001, Ukraine

Location

Ivano-Frankivsk

Ivano-Frankivsk, 76018, Ukraine

Location

Kharkiv

Kharkiv, 61052, Ukraine

Location

Kiev

Kiev, 03148, Ukraine

Location

Kiev

Kiev, 04053, Ukraine

Location

Kiev

Kiev, 04112, Ukraine

Location

Vinnytsya

Vinnytsia, 21101, Ukraine

Location

Zaporizhzhya

Zaporizhzhya, 69065, Ukraine

Location

Zaporizhzhya

Zaporizhzhya, 69068, Ukraine

Location

Zaporizhzhya

Zaporizhzhya, 69071, Ukraine

Location

Zaporizhzhya

Zaporizhzhya, 69663, Ukraine

Location

Related Publications (4)

• Giudice LC, As-Sanie S, Arjona Ferreira JC, Becker CM, Abrao MS, Lessey BA, Dynowski K, Wilk K, Li Y, Mathur V, Wagman RB, Johnson NP. A Plain Language Summary to learn about relugolix combination therapy for the treatment of pain associated with endometriosis. Pain Manag. 2023 Nov;13(11):631-640. doi: 10.2217/pmt-2023-0052. Epub 2023 Nov 20.

  PMID: 37982388 DERIVED

• Hunsche E, Gauthier M, Witherspoon B, Rakov V, Agarwal SK. Endometriosis Symptoms and Their Impacts on the Daily Lives of US Women: Results from an Interview Study. Int J Womens Health. 2023 Jun 1;15:893-904. doi: 10.2147/IJWH.S409733. eCollection 2023.

  PMID: 37283994 DERIVED

• Giudice LC, As-Sanie S, Arjona Ferreira JC, Becker CM, Abrao MS, Lessey BA, Brown E, Dynowski K, Wilk K, Li Y, Mathur V, Warsi QA, Wagman RB, Johnson NP. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet. 2022 Jun 18;399(10343):2267-2279. doi: 10.1016/S0140-6736(22)00622-5.

  PMID: 35717987 DERIVED

• Rolla E. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Res. 2019 Apr 23;8:F1000 Faculty Rev-529. doi: 10.12688/f1000research.14817.1. eCollection 2019.

  PMID: 31069056 DERIVED

MeSH Terms

Conditions

Endometriosis; Pain; Dysmenorrhea

Interventions

relugolix; estradiol, norethindrone drug combination; Estradiol

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances; Pathologic Processes; Pelvic Pain

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Myovant Medical Monitor

  Myovant Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: July 2, 2017
• Study Start: December 7, 2017
• Primary Completion: June 9, 2020
• Study Completion: April 8, 2021
• Last Updated: June 28, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (5); US (43); CA (3); FI (3); PL (13); CZ (6); UA (14); ES (2); BE (4); PT (5); BU (9); HU (12); AR (4)