Study of the Safety and Contraceptive Efficacy of Relugol... | NCT04756037

Status Module

Label	Type	Description	Intervention Names
Relugolix/E2/NETA	Experimental	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).	Drug: Relugolix Combination Therapy

Name	Type	Description	Arm Group Labels	Other Names
Relugolix Combination Therapy	Drug	Participants will receive orally 1 fixed-dose combination tablet (relugolix 40 mg/E2 1 mg/NETA 0.5 mg) once daily.	Relugolix/E2/NETA

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI)	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.	13 consecutive 28-day treatment cycles

Secondary Outcomes

Measure	Description	Time Frame
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI	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.

Eligibility Module

Eligibility Criteria

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:
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
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.

Facility	Status	City	State	ZIP	Country	Contacts
Mobile		Mobile	Alabama	36604	United States
Chandler

PubMed Identifier	Type	Citation	Retractions
37103532	Derived	Neblett MF 2nd, Stewart EA. Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Uterine Leiomyomas. Obstet Gynecol. 2023 May 1;141(5):901-910. doi: 10.1097/AOG.0000000000005145. Epub 2023 Apr 5.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 21, 2022	Feb 17, 2026

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00038.6± 6.77

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

<=35 years

Title	Measurements
	BG000352

> 35 years

Title	Measurements
	BG000

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001125
Male	BG0000

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG000317
Not Hispanic or Latino	BG000798

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0003
Asian	BG00024

Region of Enrollment

Number

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0001125

Body Mass Index (BMI) Category (kg/m2)

Count of Participants

Participants

Title

Denominators

Categories

< 30

Title	Measurements
	BG000564

>= 30

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI)

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.

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.

Posted

Number

95% Confidence Interval

Pregnancies per 100 woman-years

13 consecutive 28-day treatment cycles

ID	Title	Description
OG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Units	Counts
Participants	OG000981

Title

Denominators

Categories

Title	Measurements
	OG0001.27(0.55 to 2.50)

Secondary

Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI

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.

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.

Posted

Number

95% Confidence Interval

Pregnancies per 100 woman-years

13 consecutive 28-day treatment cycles

ID	Title	Description
OG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Units	Counts
Participants

Secondary

Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Gross PI

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.

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.

Posted

Number

95% Confidence Interval

Pregnancies per 100 woman-years

13 consecutive 28-day treatment cycles

ID	Title	Description
OG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Units	Counts
Participants	OG000

Secondary

Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Method Failure PI

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.

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.

Posted

Number

95% Confidence Interval

Pregnancies per 100 woman-years

13 consecutive 28-day treatment cycles

ID	Title	Description
OG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Units	Counts
Participants	OG000

Secondary

Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Cumulative 1-Year Pregnancy Rates

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.

Posted

Number

95% Confidence Interval

percent

13 consecutive 28-day treatment cycles

ID	Title	Description
OG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Units	Counts
Participants	OG000

Secondary

Number of Participants Who Do Not Complete 13 Treatment Cycles

Proportion of enrolled participants who do not complete 13 treatment cycles. Treatment cycle is defined as consecutive 28-day period

Enrolled Population - is defined as all patients who have completed the informed consent process, completed screening procedures, and have been allocated to treatment.

Posted

Count of Participants

Participants

13 consecutive 28-day treatment cycles

ID	Title	Description
OG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Units	Counts
Participants	OG000

Secondary

Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment

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.

The safety population is defined as all enrolled patients who receive at least one dose of study intervention.

Posted

Least Squares Mean

Standard Error

percentage change from baseline

Up to 12 months

ID	Title	Description
OG000	Relugolix/E2/NETA	Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Gastrointestinal oedema	Gastrointestinal disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Chest pain	General disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Oedema peripheral	General disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 28.0	Systematic Assessment	EG0003 events3 affected1,125 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Appendicitis	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Rotavirus infection	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Salmonellosis	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Hepatic enzyme increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 28.0	Systematic Assessment	EG0002 events1 affected1,125 at risk
Postictal paralysis	Nervous system disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Syncope	Nervous system disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 28.0	Systematic Assessment	EG0004 events4 affected1,125 at risk
Heavy menstrual bleeding	Reproductive system and breast disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk
Respiratory alkalosis	Respiratory, thoracic and mediastinal disorders	MedDRA 28.0	Systematic Assessment	EG0001 events1 affected1,125 at risk

ID	Term
D009379	Neoplasms, Muscle Tissue
D018204	Neoplasms, Connective and Soft Tissue
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 28.0	Systematic Assessment	EG00079 events75 affected1,125 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 28.0	Systematic Assessment	EG00063 events51 affected1,125 at risk
Amenorrhoea	Reproductive system and breast disorders	MedDRA 28.0	Systematic Assessment	EG00042 events41 affected1,125 at risk