Contraception
Conditions
Keywords
Relugolix, Estradiol, Norethindrone acetate, Uterine Fibroids, Endometriosis
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).
Interventions
DRUGRelugolix Combination Therapy
Participants will receive orally 1 fixed-dose combination tablet (relugolix 40 mg/E2 1 mg/NETA 0.5 mg) once daily.
Sponsors
Sumitomo Pharma Switzerland GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 Cumulative 1-Year Pregnancy Rates | 13 consecutive 28-day treatment cycles | Cumulative 1-year pregnancy rate and the associated 95% CI will be estimated on each of the efficacy analysis populations by the Kaplan-Meier (KM) survival analysis. |
| Number of Participants Who Do Not Complete 13 Treatment Cycles | 13 consecutive 28-day treatment cycles | Proportion of enrolled participants who do not complete 13 treatment cycles. Treatment cycle is defined as consecutive 28-day period |
| Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment | Up to 12 months | 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. |
Countries
Puerto Rico, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 6.77 |
| Age, Customized <=35 years | 352 Participants |
| Age, Customized > 35 years | 773 Participants |
| Body Mass Index (BMI) Category (kg/m2) < 30 | 564 Participants |
| Body Mass Index (BMI) Category (kg/m2) >= 30 | 561 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 317 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 798 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 24 Participants |
| Race (NIH/OMB) Black or African American | 575 Participants |
| Race (NIH/OMB) More than one race | 24 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 46 Participants |
| Race (NIH/OMB) White | 448 Participants |
| Region of Enrollment United States | 1125 Participants |
| Sex: Female, Male Female | 1125 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,125 |
| other Total, other adverse events | 144 / 1,125 |
| serious Total, serious adverse events | 22 / 1,125 |
Outcome results
None listed