Clinical trial NCT04756037: Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy
Official title: A Phase 3, Single-Arm, Open-Label Study to Evaluate the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are 18 to 50 Years of Age and at Risk for Pregnancy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Contraception
Keywords: Relugolix
Estradiol
Norethindrone acetate
Uterine Fibroids
Endometriosis
Lead sponsor: Sumitomo Pharma Switzerland GmbH
Sponsor class: INDUSTRY
First posted: 2021-02-16
Enrollment: 1020
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the contraceptive efficacy of relugolix combination therapy.

Detailed description: This is a single-arm, open-label, phase 3 study to assess the contraceptive efficacy of relugolix combination therapy (relugolix 40 milligrams \[mg\], estradiol \[E2\] 1 mg, and norethindrone acetate \[NETA\] 0.5 mg).

Eligibility criteria: Key Inclusion Criteria:

1. Is a premenopausal woman, 18 to 50 years of age.
2. Is at risk of pregnancy (that is, having heterosexual intercourse at least once per month) and is seeking contraception.
3. Has normal, regular menstrual cycles that are between 21 and 35 days in duration.
4. Has a diagnosis of uterine fibroids or endometriosis meeting either of the following criteria:

   1. Diagnosis of uterine fibroids by confirmation of ultrasound performed in the last 2 years and patient report of heavy menstrual bleeding affecting quality of life.
   2. Diagnosis of endometriosis and has had surgical or direct visualization (laparoscopy or laparotomy) and/or histopathologic confirmation of endometriosis, and the patient reports moderate, severe, or very severe pain during the most recent menses and/or during nonmenstrual portion of the cycle in the prior month
5. Is willing to use the study intervention as the sole method of contraception for 13 consecutive 28-day treatment cycles and does not intend to use any other form of contraception (for example, condoms).

Key Exclusion Criteria:

1. Is pregnant, or breastfeeding, or has breastfed in the last year.
2. Has a known history of infertility or sub-fertility.
3. Has presence or history of a venous thromboembolic event (for example, deep vein thrombosis, pulmonary embolism), an arterial thrombotic or thromboembolic event (for example, myocardial infarction, stroke, or peripheral arterial), or a transient ischemic attack, angina pectoris, or claudication.
4. Has a higher risk of arterial, venous thrombotic, or thromboembolic disorders.
5. Has a history of migraine with aura or focal neurological symptoms.
6. Has uncontrolled hypertension, diabetes with inadequate control, or multiple cardiovascular risk factors.
7. Has a history of clinically significant ventricular arrhythmias.
8. Has clinically significant liver disease, including active viral hepatitis or cirrhosis.
9. Has a history of pancreatitis associated with severe hypertriglyceridemia.
10. Has known human immunodeficiency virus (HIV) infection or high risk of contracting HIV.
11. Has a hepatic hemangioma or has a history of cholestasis with prior estrogen use or during pregnancy.
12. Has a serious contraindication to pregnancy (for example, a medical condition or use of chronic medication such as isotretinoin or thalidomide).
13. History of suicidal ideation or behavior, or confirmed "yes" to any question (with exception of non-suicidal self-injurious behavior, unless deemed as an unacceptable risk by the investigator) on the C-SSRS.
14. Has a bone mineral density Z-score ≤ -2.0 at lumbar spine, femoral neck, or total hip during the screening period.
15. Has a history of or currently has osteoporosis, or other metabolic bone disease, collagen vascular disease, chronic kidney disease (CKD) stage 3 or greater with glomerular filtration rate (GFR) \< 60 mL/min/m2 using Modification of Diet in Renal Disease (MDRD) method, hyperparathyroidism, hyperprolactinemia, known pituitary adenoma, hyperthyroidism, anorexia nervosa, abnormal bone mineral metabolism (eg, hypophosphatemia), or low traumatic (fragility) fracture.
16. Has used chronic glucocorticoids that are oral, parenteral, inhaled (prednisone equivalents of ≥ 2.5 mg daily for ≥ 3 months) in 12 months prior to the study.
17. Has known BRCA mutation or other mutation associated with increased risk of breast cancer.

Primary outcomes:
measure: Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI)
timeFrame: 13 consecutive 28-day treatment cycles
Secondary outcomes:
measure: Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI
timeFrame: 13 consecutive 28-day treatment cycles
measure: Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Gross PI
timeFrame: 13 consecutive 28-day treatment cycles
measure: Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Method Failure PI
timeFrame: 13 consecutive 28-day treatment cycles
measure: Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Cumulative 1-Year Pregnancy Rates
timeFrame: 13 consecutive 28-day treatment cycles
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 54 Weeks
measure: Number of Participants Who Do Not Complete 13 Treatment Cycles
timeFrame: 13 consecutive 28-day treatment cycles
measure: Percent Change in Bone Mineral Density from Baseline to 6 and 12 Months On-Treatment
timeFrame: 12 Months On-Treatment or EOT
measure: Percent Change in Bone Mineral Density from Baseline an 12 Months On-Treatment (or EOT) to 6 and 12 Months Post-Treatment
timeFrame: 12 Months Post-Treatment Follow-Up
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile
state: Alabama
city: Chandler
country: United States
facility: Chandler
state: Arizona
city: Mesa
country: United States
facility: Mesa
state: Arizona
city: Peoria
country: United States
facility: Peoria
state: Arizona
city: Phoenix
country: United States
facility: Phoenix
state: Arizona
city: Burbank
country: United States
facility: Burbank
state: California
city: Canoga Park
country: United States
facility: Canoga Park
state: California
city: Encinitas
country: United States
facility: Encinitas
state: California
city: Gardena
country: United States
facility: Gardena
state: California
city: Lancaster
country: United States
facility: Lancaster
state: California
city: Long Beach
country: United States
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state: California
city: Long Beach
country: United States
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state: California
city: Palo Alto
country: United States
facility: Palo Alto
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city: Sacramento
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city: Valley Village
country: United States
facility: Valley Village
state: California
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country: United States
facility: West Covina
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city: Aurora
country: United States
facility: Aurora
state: Colorado
city: Greenwood Village
country: United States
facility: Greenwood Village
state: Colorado
city: Washington
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state: District of Columbia
city: Washington
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state: District of Columbia
city: Aventura
country: United States
facility: Aventura
state: Florida
city: Boynton Beach
country: United States
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city: Davie
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city: Deland
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city: Hialeah
country: United States
facility: Hialeah
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city: Jacksonville
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city: Kissimmee
country: United States
facility: Kissimmee
state: Florida
city: Lake Worth
country: United States
facility: Lake Worth
state: Florida
city: Loxahatchee
country: United States
facility: Loxahatchee
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city: Margate
country: United States
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city: Miami
country: United States
facility: Miami
state: Florida
city: Miami
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
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city: New Port Richey
country: United States
facility: New Port Richey
state: Florida
city: Orlando
country: United States
facility: Orlando
state: Florida
city: Orlando
country: United States
facility: Orlando
state: Florida
city: Panama City
country: United States
facility: Panama City
state: Florida
city: Sarasota
country: United States
facility: Sarasota
state: Florida
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: College Park
country: United States
facility: College Park
state: Georgia
city: Columbus
country: United States
facility: Columbus
state: Georgia
city: Norcross
country: United States
facility: Norcross
state: Georgia
city: Sandy Springs
country: United States
facility: Sandy Springs
state: Georgia
city: Savannah
country: United States
facility: Savannah
state: Georgia
city: Smyrna
country: United States
facility: Smyrna
state: Georgia
city: Meridian
country: United States
facility: Meridian
state: Idaho
city: Nampa
country: United States
facility: Nampa
state: Idaho
city: Chicago
country: United States
facility: Chicago
state: Illinois
city: Chicago
country: United States
facility: Chicago
state: Illinois
city: Brownsburg
country: United States
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state: Indiana
city: Mishawaka
country: United States
facility: Mishawaka
state: Indiana
city: Shawnee
country: United States
facility: Shawnee
state: Kansas
city: Covington
country: United States
facility: Covington
state: Louisiana
city: Marrero
country: United States
facility: Marrero
state: Louisiana
city: Metairie
country: United States
facility: Metairie
state: Louisiana
city: New Orleans
country: United States
facility: New Orleans
state: Louisiana
city: Shreveport
country: United States
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state: Louisiana
city: Baltimore
country: United States
facility: Baltimore
state: Maryland
city: Towson
country: United States
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state: Maryland
city: Dearborn Heights
country: United States
facility: Dearborn Heights
state: Michigan
city: Detroit
country: United States
facility: Detroit
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city: Saginaw
country: United States
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state: Michigan
city: Jackson
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facility: Jackson
state: Mississippi
city: Saint Louis
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state: Missouri
city: Saint Louis
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state: Missouri
city: Las Vegas
country: United States
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state: Nevada
city: Las Vegas
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state: Nevada
city: North Las Vegas
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facility: North Las Vegas
state: Nevada
city: Cherry Hill
country: United States
facility: Cherry Hill
state: New Jersey
city: Albuquerque
country: United States
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state: New Mexico
city: New York
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state: New York
city: Durham
country: United States
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state: North Carolina
city: New Bern
country: United States
facility: New Bern
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh
state: North Carolina
city: Winston-Salem
country: United States
facility: Winston-Salem
state: North Carolina
city: Minot
country: United States
facility: Minot
state: North Dakota
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Fairfield
country: United States
facility: Fairfield
state: Ohio
city: Franklin
country: United States
facility: Franklin
state: Ohio
city: Portland
country: United States
facility: Portland
state: Oregon
city: Philadelphia
country: United States
facility: Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Myrtle Beach
state: South Carolina
city: Summerville
country: United States
facility: Summerville
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga
state: Tennessee
city: Memphis
country: United States
facility: Memphis
state: Tennessee
city: Austin
country: United States
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state: Texas
city: Beaumont
country: United States
facility: Beaumont
state: Texas
city: Dallas
country: United States
facility: Dallas
state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: League City
country: United States
facility: League City
state: Texas
city: Pearland
country: United States
facility: Pearland
state: Texas
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Salt Lake City
state: Utah
city: Annandale
country: United States
facility: Annandale
state: Virginia
city: Norfolk
country: United States
facility: Norfolk
state: Virginia
city: Bellevue
country: United States
facility: Bellevue
state: Washington
city: Seattle
country: United States
facility: Seattle
state: Washington
city: Cidra
country: Puerto Rico
facility: Cidra
city: San Juan
country: Puerto Rico
facility: San Juan
city: San Juan
country: Puerto Rico
facility: San Juan
Study officials:
References: