Trial Outcomes & Findings for Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy (NCT NCT04756037)
NCT ID: NCT04756037
Last Updated: 2026-05-13
Results Overview
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.
COMPLETED
PHASE3
1164 participants
13 consecutive 28-day treatment cycles
2026-05-13
Participant Flow
Participant milestones
| Measure |
Relugolix/E2/NETA
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Overall Study
STARTED
|
1164
|
|
Overall Study
COMPLETED
|
497
|
|
Overall Study
NOT COMPLETED
|
667
|
Reasons for withdrawal
| Measure |
Relugolix/E2/NETA
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Overall Study
Adverse Event
|
93
|
|
Overall Study
Lost to Follow-up
|
94
|
|
Overall Study
Physician Decision
|
17
|
|
Overall Study
Pregnancy
|
6
|
|
Overall Study
Protocol Violation
|
44
|
|
Overall Study
Withdrawal by Subject
|
77
|
|
Overall Study
Bone loss meeting the threshold for withdrawal per protocol
|
193
|
|
Overall Study
Other not specified in protocol
|
27
|
|
Overall Study
Withdrawal of consent
|
77
|
|
Overall Study
Patients who did not take any treatment
|
39
|
Baseline Characteristics
Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy
Baseline characteristics by cohort
| Measure |
Relugolix/E2/NETA
n=1125 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Age, Continuous
|
38.6 years
STANDARD_DEVIATION 6.77 • n=1512 Participants
|
|
Age, Customized
<=35 years
|
352 Participants
n=1512 Participants
|
|
Age, Customized
> 35 years
|
773 Participants
n=1512 Participants
|
|
Sex: Female, Male
Female
|
1125 Participants
n=1512 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=1512 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
317 Participants
n=1512 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
798 Participants
n=1512 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
10 Participants
n=1512 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=1512 Participants
|
|
Race (NIH/OMB)
Asian
|
24 Participants
n=1512 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
5 Participants
n=1512 Participants
|
|
Race (NIH/OMB)
Black or African American
|
575 Participants
n=1512 Participants
|
|
Race (NIH/OMB)
White
|
448 Participants
n=1512 Participants
|
|
Race (NIH/OMB)
More than one race
|
24 Participants
n=1512 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
46 Participants
n=1512 Participants
|
|
Region of Enrollment
United States
|
1125 Participants
n=1512 Participants
|
|
Body Mass Index (BMI) Category (kg/m2)
< 30
|
564 Participants
n=1512 Participants
|
|
Body Mass Index (BMI) Category (kg/m2)
>= 30
|
561 Participants
n=1512 Participants
|
PRIMARY outcome
Timeframe: 13 consecutive 28-day treatment cyclesPopulation: Restricted Intent-to-treat Population is defined as the subset of patients included in the ITT population (defined as all patients who have completed the informed consent process, completed screening procedures, and have been allocated to treatment and receive at least one dose of study intervention.) who have at least one at-risk treatment cycle or who have a treatment cycle (at-risk or not) in which a pregnancy has occurred. Patients are aged between \>= 18 years to \<=50 years.
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.
Outcome measures
| Measure |
Relugolix/E2/NETA
n=981 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI)
|
1.27 Pregnancies per 100 woman-years
Interval 0.55 to 2.5
|
SECONDARY outcome
Timeframe: 13 consecutive 28-day treatment cyclesPopulation: The Modified Intent-to-Treat (mITT) population is defined as the subset of patients included in the ITT(all patients who have completed the ICF process, completed screening procedures, and have been allocated to treatment and receive at least one dose of study intervention) who have at least one treatment cycle without use of other contraceptive methods or patients with a treatment cycle (at-risk or not) in which a pregnancy has occurred. Patients are aged between \>= 18 years to \<=50 years.
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.
Outcome measures
| Measure |
Relugolix/E2/NETA
n=1024 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI
|
1.10 Pregnancies per 100 woman-years
Interval 0.47 to 2.16
|
SECONDARY outcome
Timeframe: 13 consecutive 28-day treatment cyclesPopulation: The ITT population is defined as all enrolled patients who receive at least one dose of study intervention. Patients are aged between \>= 18 years to \<=50 years.
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.
Outcome measures
| Measure |
Relugolix/E2/NETA
n=1125 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Gross PI
|
1.04 Pregnancies per 100 woman-years
Interval 0.45 to 2.06
|
SECONDARY outcome
Timeframe: 13 consecutive 28-day treatment cyclesPopulation: The Per Protocol (PP) population is defined as the subset of patients in the Restricted Intent-to-treat (rITT) population with at least one treatment cycle and without meeting prespecified important protocol deviations. Patients are aged between \>= 18 years to \<=50 years.
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.
Outcome measures
| Measure |
Relugolix/E2/NETA
n=914 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Method Failure PI
|
0.64 Pregnancies per 100 woman-years
Interval 0.13 to 1.88
|
SECONDARY outcome
Timeframe: 13 consecutive 28-day treatment cyclesPopulation: Restricted Intent-to-treat Population is defined as the subset of patients included in the ITT population (defined as all patients who have completed the informed consent process, completed screening procedures, and have been allocated to treatment and receive at least one dose of study intervention.) who have at least one at-risk treatment cycle or who have a treatment cycle (at-risk or not) in which a pregnancy has occurred.
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.
Outcome measures
| Measure |
Relugolix/E2/NETA
n=981 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Cumulative 1-Year Pregnancy Rates
|
1.2 percent
Interval 0.6 to 2.3
|
SECONDARY outcome
Timeframe: 13 consecutive 28-day treatment cyclesPopulation: Enrolled Population - is defined as all patients who have completed the informed consent process, completed screening procedures, and have been allocated to treatment.
Proportion of enrolled participants who do not complete 13 treatment cycles. Treatment cycle is defined as consecutive 28-day period
Outcome measures
| Measure |
Relugolix/E2/NETA
n=1164 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Number of Participants Who Do Not Complete 13 Treatment Cycles
|
667 Participants
|
SECONDARY outcome
Timeframe: Up to 12 monthsPopulation: The safety population is defined as all enrolled patients who receive at least one dose of study intervention.
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.
Outcome measures
| Measure |
Relugolix/E2/NETA
n=1125 Participants
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment
Lumber Spine (Month 6)
|
-0.65 percentage change from baseline
Standard Error 0.092
|
|
Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment
Lumber Spine (Month 12)
|
-0.72 percentage change from baseline
Standard Error 0.116
|
|
Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment
Total Hip (Month 6)
|
-0.36 percentage change from baseline
Standard Error 0.081
|
|
Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment
Total Hip (Month 12)
|
-0.47 percentage change from baseline
Standard Error 0.101
|
|
Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment
Femoral neck (Month 6)
|
-0.36 percentage change from baseline
Standard Error 0.124
|
|
Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment
Femoral neck (Month 12)
|
-0.56 percentage change from baseline
Standard Error 0.138
|
Adverse Events
Relugolix/E2/NETA
Serious adverse events
| Measure |
Relugolix/E2/NETA
n=1125 participants at risk
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Gastrointestinal disorders
Gastrointestinal oedema
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
General disorders
Chest pain
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
General disorders
Oedema peripheral
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.27%
3/1125 • Number of events 3 • up to 12 months
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Infections and infestations
Appendicitis
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Infections and infestations
COVID-19 pneumonia
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Infections and infestations
Gastrointestinal infection
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Infections and infestations
Rotavirus infection
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Infections and infestations
Salmonellosis
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Investigations
Hepatic enzyme increased
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.09%
1/1125 • Number of events 2 • up to 12 months
|
|
Nervous system disorders
Postictal paralysis
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Nervous system disorders
Syncope
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Psychiatric disorders
Suicidal ideation
|
0.36%
4/1125 • Number of events 4 • up to 12 months
|
|
Reproductive system and breast disorders
Heavy menstrual bleeding
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory alkalosis
|
0.09%
1/1125 • Number of events 1 • up to 12 months
|
Other adverse events
| Measure |
Relugolix/E2/NETA
n=1125 participants at risk
Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).
|
|---|---|
|
Nervous system disorders
Headache
|
6.7%
75/1125 • Number of events 79 • up to 12 months
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
4.5%
51/1125 • Number of events 63 • up to 12 months
|
|
Reproductive system and breast disorders
Amenorrhoea
|
3.6%
41/1125 • Number of events 42 • up to 12 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place