Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy
- Conditions
- Contraception
- Interventions
- Registration Number
- NCT04756037
- Lead Sponsor
- Sumitomo Pharma Switzerland GmbH
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 1020
-
Is a premenopausal woman, 18 to 50 years of age.
-
Is at risk of pregnancy (that is, having heterosexual intercourse at least once per month) and is seeking contraception.
-
Has normal, regular menstrual cycles that are between 21 and 35 days in duration.
-
Has a diagnosis of uterine fibroids or endometriosis meeting either of the following criteria:
- 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.
- 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
-
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
- Is pregnant, or breastfeeding, or has breastfed in the last year.
- Has a known history of infertility or sub-fertility.
- 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.
- Has a higher risk of arterial, venous thrombotic, or thromboembolic disorders.
- Has a history of migraine with aura or focal neurological symptoms.
- Has uncontrolled hypertension, diabetes with inadequate control, or multiple cardiovascular risk factors.
- Has a history of clinically significant ventricular arrhythmias.
- Has clinically significant liver disease, including active viral hepatitis or cirrhosis.
- Has a history of pancreatitis associated with severe hypertriglyceridemia.
- Has known human immunodeficiency virus (HIV) infection or high risk of contracting HIV.
- Has a hepatic hemangioma or has a history of cholestasis with prior estrogen use or during pregnancy.
- Has a serious contraindication to pregnancy (for example, a medical condition or use of chronic medication such as isotretinoin or thalidomide).
- 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.
- Has a bone mineral density Z-score ≤ -2.0 at lumbar spine, femoral neck, or total hip during the screening period.
- 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.
- 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.
- Has known BRCA mutation or other mutation associated with increased risk of breast cancer.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Relugolix/E2/NETA Relugolix Combination Therapy Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
- Primary Outcome Measures
Name Time Method Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI) 13 consecutive 28-day treatment cycles The At-Risk PI is defined as the number of on treatment pregnancies per 100 women-years of treatment. The At-Risk PI will be calculated on the basis of cycles considered at-risk of pregnancy, that is, consecutive 28-day periods without use of any other contraceptive methods and with affirmed occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
- Secondary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events 54 Weeks Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Method Failure PI 13 consecutive 28-day treatment cycles The "perfect use" contraceptive efficacy will be assessed using the Method Failure PI, based on the number of on-treatment pregnancies occurring during cycles that are at risk and without major protocol deviations. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI 13 consecutive 28-day treatment cycles The Modified At-Risk PI is based on the number of on-treatment pregnancies occurring during cycles without any other contraceptive methods, regardless of occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Gross PI 13 consecutive 28-day treatment cycles The "typical use" contraceptive efficacy will be assessed using the Gross PI, based on the number of on-treatment pregnancies occurring during all cycles regardless of the use of other contraceptive methods, confirmed vaginal intercourse, or protocol compliance. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Cumulative 1-Year Pregnancy Rates 13 consecutive 28-day treatment cycles Percent Change in Bone Mineral Density from Baseline an 12 Months On-Treatment (or EOT) to 6 and 12 Months Post-Treatment 12 Months Post-Treatment Follow-Up The percent change in bone mineral density will be measured from baseline and 12-months on-treatment (or End-of-Treatment) to 6- and 12-months post-treatment at the lumbar spine (L1-L4), total hip, and femoral neck.
Number of Participants Who Do Not Complete 13 Treatment Cycles 13 consecutive 28-day treatment cycles Percent Change in Bone Mineral Density from Baseline to 6 and 12 Months On-Treatment 12 Months On-Treatment or EOT The percent change in bone mineral density will be measured from baseline to 6- and 12-months on treatment at the lumbar spine (L1-L4), total hip, and femoral neck.
Trial Locations
- Locations (93)
Encinitas
🇺🇸Encinitas, California, United States
Gardena
🇺🇸Gardena, California, United States
Burbank
🇺🇸Burbank, California, United States
Canoga Park
🇺🇸Canoga Park, California, United States
Mobile
🇺🇸Mobile, Alabama, United States
Chandler
🇺🇸Chandler, Arizona, United States
Mesa
🇺🇸Mesa, Arizona, United States
Peoria
🇺🇸Peoria, Arizona, United States
Phoenix
🇺🇸Phoenix, Arizona, United States
Lancaster
🇺🇸Lancaster, California, United States
Long Beach
🇺🇸Long Beach, California, United States
Palo Alto
🇺🇸Palo Alto, California, United States
Sacramento
🇺🇸Sacramento, California, United States
San Diego
🇺🇸San Diego, California, United States
San Fernando
🇺🇸San Fernando, California, United States
Valley Village
🇺🇸Valley Village, California, United States
West Covina
🇺🇸West Covina, California, United States
Aurora
🇺🇸Aurora, Colorado, United States
Greenwood Village
🇺🇸Greenwood Village, Colorado, United States
Washington
🇺🇸Washington, District of Columbia, United States
Aventura
🇺🇸Aventura, Florida, United States
Boynton Beach
🇺🇸Boynton Beach, Florida, United States
Davie
🇺🇸Davie, Florida, United States
Deland
🇺🇸Deland, Florida, United States
Hialeah
🇺🇸Hialeah, Florida, United States
Jacksonville
🇺🇸Jacksonville, Florida, United States
Kissimmee
🇺🇸Kissimmee, Florida, United States
Lake Worth
🇺🇸Lake Worth, Florida, United States
Loxahatchee
🇺🇸Loxahatchee, Florida, United States
Margate
🇺🇸Margate, Florida, United States
Miami
🇺🇸Miami, Florida, United States
New Port Richey
🇺🇸New Port Richey, Florida, United States
Orlando
🇺🇸Orlando, Florida, United States
Panama City
🇺🇸Panama City, Florida, United States
Sarasota
🇺🇸Sarasota, Florida, United States
Atlanta
🇺🇸Atlanta, Georgia, United States
College Park
🇺🇸College Park, Georgia, United States
Columbus
🇺🇸Columbus, Ohio, United States
Norcross
🇺🇸Norcross, Georgia, United States
Sandy Springs
🇺🇸Sandy Springs, Georgia, United States
Savannah
🇺🇸Savannah, Georgia, United States
Smyrna
🇺🇸Smyrna, Georgia, United States
Meridian
🇺🇸Meridian, Idaho, United States
Nampa
🇺🇸Nampa, Idaho, United States
Chicago
🇺🇸Chicago, Illinois, United States
Brownsburg
🇺🇸Brownsburg, Indiana, United States
Mishawaka
🇺🇸Mishawaka, Indiana, United States
Shawnee
🇺🇸Shawnee, Kansas, United States
Covington
🇺🇸Covington, Louisiana, United States
Marrero
🇺🇸Marrero, Louisiana, United States
Metairie
🇺🇸Metairie, Louisiana, United States
New Orleans
🇺🇸New Orleans, Louisiana, United States
Shreveport
🇺🇸Shreveport, Louisiana, United States
Baltimore
🇺🇸Baltimore, Maryland, United States
Towson
🇺🇸Towson, Maryland, United States
Dearborn Heights
🇺🇸Dearborn Heights, Michigan, United States
Detroit
🇺🇸Detroit, Michigan, United States
Saginaw
🇺🇸Saginaw, Michigan, United States
Jackson
🇺🇸Jackson, Mississippi, United States
Saint Louis
🇺🇸Saint Louis, Missouri, United States
Las Vegas
🇺🇸Las Vegas, Nevada, United States
North Las Vegas
🇺🇸North Las Vegas, Nevada, United States
Cherry Hill
🇺🇸Cherry Hill, New Jersey, United States
Albuquerque
🇺🇸Albuquerque, New Mexico, United States
New York
🇺🇸New York, New York, United States
Durham
🇺🇸Durham, North Carolina, United States
New Bern
🇺🇸New Bern, North Carolina, United States
Raleigh
🇺🇸Raleigh, North Carolina, United States
Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
Minot
🇺🇸Minot, North Dakota, United States
Fairfield
🇺🇸Fairfield, Ohio, United States
Franklin
🇺🇸Franklin, Ohio, United States
Portland
🇺🇸Portland, Oregon, United States
Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Myrtle Beach
🇺🇸Myrtle Beach, South Carolina, United States
Summerville
🇺🇸Summerville, South Carolina, United States
Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Memphis
🇺🇸Memphis, Tennessee, United States
Austin
🇺🇸Austin, Texas, United States
Beaumont
🇺🇸Beaumont, Texas, United States
Dallas
🇺🇸Dallas, Texas, United States
Fort Worth
🇺🇸Fort Worth, Texas, United States
Houston
🇺🇸Houston, Texas, United States
League City
🇺🇸League City, Texas, United States
Pearland
🇺🇸Pearland, Texas, United States
San Antonio
🇺🇸San Antonio, Texas, United States
Salt Lake City
🇺🇸Salt Lake City, Utah, United States
Annandale
🇺🇸Annandale, Virginia, United States
Norfolk
🇺🇸Norfolk, Virginia, United States
Bellevue
🇺🇸Bellevue, Washington, United States
Seattle
🇺🇸Seattle, Washington, United States
Cidra
🇵🇷Cidra, Puerto Rico
San Juan
🇵🇷San Juan, Puerto Rico