Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy

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).

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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.