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

Phase 3CompletedNCT03204318

Myovant Sciences GmbH638 enrolled

Overview

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.

This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral, once-daily relugolix (40 mg) co-administered with either 12 or 24 weeks of low-dose E2 (1.0 mg) and NETA (0.5 mg), compared with placebo. Approximately 600 women with endometriosis-associated pain will be enrolled and randomized 1:1:1 to Group A - relugolix plus low-dose hormonal add-back therapy, Group B - relugolix monotherapy for 12 weeks followed by co-administration with low-dose hormonal add-back therapy, or Group C - placebo (N = 200 per group). Eligible participants were randomized on Baseline Day 1 to Treatment Group A, B, or C, in the double-blind period. Eligible participants, including those randomized to placebo, were offered the opportunity to enroll in an 80-week open-label extension study where participants received relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a Follow-Up visit approximately 30 days after the participant's last dose of study drug.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

638

Conditions

Endometriosis Related Pain

Interventions

RelugolixDRUG

Relugolix 40-mg tablet administered orally once daily.

Estradiol/norethindrone acetateDRUG

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

Estradiol/norethindrone acetate placeboDRUG

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.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 50 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of the informed consent form. 2. Has agreed to use only study-specified analgesic medications during the study and is not known to be intolerant to these. 3. 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. 4. 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 1. Mean NMPP NRS score ≥ 2.5, or 2. Mean NMPP NRS score ≥ 1.25 and NMPP NRS score ≥ 5.0 on ≥ 4 days. Key Exclusion Criteria: 1. Has a history of chronic pelvic pain that is not caused by endometriosis. 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 had surgical procedures for treatment of endometriosis within the 3 months prior to the Screening visit. 4. Has a history of or currently has osteoporosis or other metabolic bone disease. 5. Has a clinically significant gynecologic condition, other than endometriosis, identified during Screening or Run-In period transvaginal ultrasound or endometrial biopsy.

Locations (123)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Week 24 or EOT

Secondary Outcomes

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

Assessed using the Pain Domain of the EHP-30 questionnaire.

Time frame: Baseline, Week 24

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

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

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

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

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

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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

Dothan

Dothan, Alabama, United States

Mesa

Mesa, Arizona, United States

Scottsdale

Scottsdale, Arizona, United States

Tucson

Tucson, Arizona, United States

Tucson

Tucson, Arizona, United States

Canoga Park

Canoga Park, California, United States

Long Beach

Long Beach, California, United States

San Diego

San Diego, California, United States

Greenwood Village

Greenwood Village, Colorado, United States

Fort Myers

Fort Myers, Florida, United States

...and 113 more locations

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

Assessed based on usage of protocol-specified opioids for endometriosis-associated pain recorded daily in an e-Diary.

Time frame: Week 24 or EOT

Change From Baseline In Dyspareunia NRS Scores At Week 24 Or EOT

Assessed using an NRS score (11-point scale) for dyspareunia recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Change From Baseline In Analgesic Use For Endometriosis-associated Pain Based On Mean Pill Count At Week 24 Or EOT

Assessed based on usage of protocol-specified analgesic for endometriosis-associated pain recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24

Assessed using the pain domain of the EHP-30 questionnaire.

Time frame: Baseline to Week 24

Dysmenorrhea Responder Rate By Month

The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.

Time frame: Baseline to Week 24

NMPP Responder Rate By Month

The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.

Time frame: Baseline to Week 24

Change In Dysmenorrhea NRS Score By Month

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.

Time frame: Baseline to Week 24

Change In NMPP NRS Score By Month

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.

Time frame: Baseline to Week 24

Change In Overall Pelvic Pain NRS Score By Month

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.

Time frame: Baseline to Week 24

Change In Dyspareunia NRS Score By Month

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary.

Time frame: Baseline to Week 24

Change From Baseline In Ibuprofen Use At Week 24 Or EOT

Assessed using ibuprofen pill counts for endometriosis-associated pain recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Change From Baseline In Opioid Use At Week 24 Or EOT

Assessed using opioid pill counts for endometriosis-associated pain recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Change From Baseline In The Mean Dysmenorrhea Functional Impairment At Week 24 Or EOT

Assessed using the subject modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Change From Baseline In The Mean NMPP Functional Impairment At Week 24 Or EOT

Assessed using the subject modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Change From Baseline In The Mean Dyspareunia Functional Impairment At Week 24 Or EOT

Assessed using the subject modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an e-Diary.

Time frame: Baseline, Week 24 or EOT

Change From Baseline In Patient Global Assessment (PGA) For Dysmenorrhea Symptom Severity At Week 24

The PGA for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle.

Time frame: Baseline, Week 24

Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Dysmenorrhea At Week 24

The PGA for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of the severity of pain during their menstrual cycle.

Time frame: Week 24

Change From Baseline In PGA For NMPP Symptom Severity At Week 24

The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.

Time frame: Baseline, Week 24

Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For NMPP At Week 24

The PGA for NMPP is a 1-item questionnaire designed to assess participants' impression of the severity of pain when they are not menstruating.

Time frame: Week 24

Change From Baseline In PGA For Pain Severity At Week 24

The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.

Time frame: Baseline, Week 24

Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Pain Severity At Week 24

The PGA for pain severity is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.

Time frame: Week 24

Change From Baseline In PGA For Function At Week 24

The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.

Time frame: Baseline, Week 24

Percentage Of Participants With Improvement, No Change, Or Worsening From Baseline In PGA For Function At Week 24

The PGA for function is a 1-item questionnaire designed to assess participants' impression of how their pain affected their usual activities.

Time frame: Week 24

Percentage Of Participants Who Are "Better" Or "Much Better" On The Patient Global Impression Of Change (PGIC) For Dysmenorrhea At Week 24

The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle.

Time frame: Week 24

Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For NMPP At Week 24

The PGIC for NMPP is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during their menstrual cycle.

Time frame: Week 24

Percentage Of Participants Who Are "Better" Or "Much Better" On The PGIC For Dyspareunia At Week 24

The PGIC for dyspareunia is a 1-item questionnaire designed to assess participants' impression of change in the severity of pain during sexual intercourse.

Time frame: Week 24

Change From Baseline In The Non-Pain Of The EHP-30 Domains At Week 24

Assessed using the non-pain domains (Control and Powerlessness, Social Support, Emotional Well-Being, and Self-Image) of the EHP-30 questionnaire.

Time frame: Baseline, Week 24

Change From Baseline In The EHP-30 Scale Total Score At Week 24

Assessed using the total score of the EHP-30 questionnaire.

Time frame: Baseline, Week 24

Change From Baseline In The EHP Work Domain Score At Week 24

The EHP Work domain is a 5-item questionnaire that assesses impact of pain on ability to work.

Time frame: Baseline, Week 24

Categorical Change From Baseline In Quality Of Life Assessed By European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Questionnaire At Week 24

The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.

Time frame: Baseline, Week 24

Change From Baseline To Week 24 In EQ-5D-5L Visual Analogue Scale Score At Week 24

The EQ-5D-5L is a 5-item questionnaire designed to assess quality of life.

Time frame: Baseline, Week 24

Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA

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.

Time frame: Week 24 or EOT

Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 24 Or EOT For Relugolix Plus Delayed E2/NETA

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.

Time frame: Week 24 or EOT

Change From Baseline In The EHP-30 Pain Score At Week 24 For Relugolix Plus Delayed E2/NETA

Assessed using the Pain Domain of the EHP-30 questionnaire.

Time frame: Baseline, Week 24

Percentage Of Participants Who Have A Reduction Of At Least 20 Points In The EHP-30 Pain Domain From Baseline To Week 24 For Relugolix Plus Delayed E2/NETA

Assessed using the pain domain of the EHP-30 questionnaire.

Time frame: Baseline to Week 24

Percentage Change From Baseline In Bone Mineral Density At The Lumbar Spine (L1-L4) At Week 12

Assessed by dual-energy X-ray absorptiometry (DXA) scan.

Time frame: Baseline, Week 12

Percentage Change From Baseline In Bone Mineral Density At Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 24

Assessed by DXA scan.

Time frame: Baseline, Week 24

Percentage Of Participants Experiencing Vasomotor Symptoms At Week 12 Between Group A And B

Time frame: Week 12

Change From Baseline In Serum Concentrations Of Luteinizing Hormone, Follicle Stimulating Hormone, Estradiol, And Progesterone

Blood samples will be collected from participants for hormonal measurements.

Time frame: Baseline, Week 24

Pre-dose Relugolix Plasma Concentrations

Blood samples will be collected from participants for relugolix measurements.

Time frame: Week 4

Endometrial Biopsy At Week 24

Primary diagnosis of endometrial biopsy assessment by pathologist.

Time frame: Week 24