Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Endometriosis

Leiomyoma

Myofibroma

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

Reproductive Control Agents

All Drugs and Chemicals

Norethindrone

Norethindrone Acetate

Estradiol

Relugolix

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Polyestradiol phosphate

Contraceptive Agents

Androgens

Androgen Antagonists

Hormones

Hormone Antagonists

Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Participants will receive orally 1 fixed-dose combination tablet (relugolix 40 mg/E2 1 mg/NETA 0.5 mg) once daily.

Relugolix Combination Therapy

The purpose of this study is to assess the contraceptive efficacy of relugolix combination therapy.

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).

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

A Phase 3, Single-Arm, Open-Label Study to Evaluate the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are 18 to 50 Years of Age and at Risk for Pregnancy

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.

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 "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 "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 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 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.

Sumitomo Pharma Switzerland GmbH

Symptoms and General Pathology

Hemorrhage

Menorrhagia

Participants prescribed Oriahnn for management of heavy menstrual bleeding (HMB) due to uterine fibroids (UF).

Participants prescribed Oriahnn for management of HMB due to UF, with meaningful hair loss.

ABBVIE INC.

Uterine Fibroids (UF) are benign smooth muscle neoplasms of the uterus that affect women of reproductive age. UFs are one of the leading causes of hospitalizations for gynecological disorders and often lead to hysterectomy. In this study, women with heavy menstrual bleeding (HMB) due to UF who are being treated with Oriahnn will be followed to establish the incidence rate, time to onset, extent, pattern, and resolution of meaningful hair loss, as well as any racial differences.

Oriahnn is an approved drug for the management of HMB associated with UF. All study participants will receive Oriahnn as prescribed by their study doctor in accordance with approved local label. Study Participants will be followed for up 24 months (part 1). Approximately 1600 participants aged 18-50 years will be enrolled at 1 site in the United States.

Participants will receive oral Oriahnn as prescribed by their physician according to their routine clinical practice and local label. Participants will be followed for 24 months.

There is expected to be no additional burden for participants in this trial. Participants will complete questionnaires on a quarterly basis.

A Study to Evaluate Changes in Hair in Adult Participants Taking Oral Oriahnn Capsules With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF)

A Prospective, Single-Arm, Descriptive Observational Study to Evaluate Changes in Hair in Women Exposed to Oriahnn® (Elagolix 300 mg BID With Estradiol 1 mg/Norethindrone Acetate 0.5 mg QD)

Meaningful hair loss is defined as patient-reported changes in thickness, fullness, or pattern of hair that results in less hair than normal or hair shedding that is increased from normal in the Hair Questionnaire.

Time from initiation of Oriahnn until patient-reported meaningful hair loss will be assessed.

Based on example description and images of alopecia subtypes, changes in patterns of hair loss are classified as primary pattern of hair loss.

Defined as a report that since the participant has reported hair loss, her hair loss has improved.

Resolution in hair loss is defined as a report that since the patient has reported hair loss, her hair has returned to normal.

Time from onset of meaningful hair loss until reported resolution.

Discontinuations of Oriahnn at or after reported hair loss will be calculated.

AbbVie

Pain

Participants will receive relugolix combination therapy orally once daily for 48 months.

A fixed-dose combination tablet containing relugolix 40 mg, estradiol (E2) 1 mg, and norethindrone acetate (NETA) 0.5 mg.

Relugolix Combination Tablet

Clinical Trials at Myovant

Myovant Medical Director

The purpose of this clinical trial to characterize changes in bone mineral density during continuous treatment with relugolix combination tablet for up to 48 months (4 years) and 1 year of post-treatment follow-up in premenopausal women with heavy menstrual bleeding associated with uterine leiomyomas (fibroids) or with moderate-to-severe pain associated with endometriosis.

A prospective, single-arm, open-label, Phase 3B study to assess the effect of continuous 48 months (4 years) of treatment with relugolix combination tablet (relugolix 40 mg/estradiol \[E2\] 1 mg/norethindrone acetate \[NETA\] 0.5 mg) on bone mineral density in premenopausal women with heavy menstrual bleeding associated with uterine leiomyomas (fibroids) and premenopausal women with moderate to severe pain associated with endometriosis.

Approximately 1000 women (500 with heavy menstrual bleeding associated with uterine fibroids and 500 with moderate to severe pain associated with endometriosis) will receive relugolix combination tablet, during which time BMD will be assessed by dual-energy X-ray absorptiometry every 6 months.

A subset of participants will be eligible to enter this study following completion of 1 year of treatment with relugolix combination therapy in MVT-601-050 (NCT04756037; SERENE) and will complete 3 years of treatment under this protocol.

Upon completion of 48 months (4 years) of treatment or after early termination of treatment, participants will enter a 1-year post-treatment follow-up period during which time bone mineral density will be assessed at Month 6 and Month 12 following treatment cessation.

A Phase 3B Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Women With Uterine Fibroids or Endometriosis

A Phase 3B, Single-Arm, Open-Label Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids or Moderate to Severe Pain Associated With Endometriosis

Assessed by dual-energy X-ray absorptiometry (DXA) scan.

Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.

Safety analyses will be conducted by each safety population: 1) women with uterine fibroids, 2) women with endometriosis, and 3) overall population. The treatment-emergent period will be defined as the period of time from the date of the first dose of the study drug through 14 days after the last dose of study drug, or the date of initiation of another investigational agent or hormonal therapy affecting the hypothalamic-pituitary gonadal axis or surgical intervention for uterine fibroids or for endometriosis, whichever occurs first.

Safety analyses will be conducted by each safety population: 1) women with uterine fibroids, 2) women with endometriosis, and 3) overall population. All adverse events will be coded to preferred term and system organ class using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0 or higher. The incidence of fractures will also be summarized by anatomical sites and whether the fracture qualifies as a fragility fracture. A participant reporting the same adverse event more than once is counted once, and at the maximum severity or strongest relationship to study drug treatment when calculating incidence.

Recurrence

Breast Neoplasms

Carcinoma in Situ

Breast Carcinoma In Situ

Breast Diseases

Skin Diseases

Menopause

Estrogens

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

Contraceptives, Oral

Contraceptives, Oral, Hormonal

therapeutic estradiol

norethindrone acetate

Lars Holmberg, MD, PhD

Jonas Bergh, MD, PhD

C. Rageth, MD, PD

Janusz Jaskiewicz, MD

RATIONALE: Hormone replacement therapy is effective for relieving symptoms of menopause. It is not yet known if hormone replacement therapy increases the risk of breast cancer recurrence in women previously treated for early stage breast cancer.

PURPOSE: Randomized phase III trial to determine the risk of breast cancer recurrence in women with previous early stage breast cancer who are receiving hormone replacement therapy for menopause symptoms.

OBJECTIVES:

* Evaluate the safety of hormone replacement therapy, in terms of risk of recurrence, in women with previously treated, nonrecurrent stage 0-II breast cancer.
* Compare this regimen vs non-hormonal symptomatic treatment, in terms of quality of life and risk of death, in this patient population.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified by center, prior hormone replacement therapy before diagnosis, and concurrent tamoxifen therapy. Patients are randomized to one of two treatment arms.

* Arm I: Patients receive one of the following: Women with an intact uterus whose last menstrual bleeding has occurred within 2 years receive continuous oral cyclic estradiol-norethindrone combination comprising estradiol only on days 1-12, estradiol plus norethindrone on days 13-22, and then estradiol only on days 22-28. Women with an intact uterus whose last menstrual bleeding occurred more than 2 years prior to study receive continuous daily oral estradiol-norethindrone combination. Women who have had a hysterectomy receive continuous daily oral estradiol only.
* Arm II: Patients receive one or more non-hormonal therapies (e.g., clonidine, beta blockers, psychological support, physical exercise, acupuncture).

Treatment in both arms continues for 2 years in the absence of disease progression. Patients may continue their randomized treatment regimen at the discretion of the treating physician.

Quality of life is assessed 3 times during the study and then every two years thereafter. Gynecological health is assessed at 3 months, 6 months, and one year during the study and then annually for at least 5 years. Breast cancer is assessed every 6 months for 3 years and then annually thereafter or at the discretion of the treating physician.

PROJECTED ACCRUAL: A total of 1,300 patients will be accrued for this study within 5-6 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy	NCT04756037	Contraception	Relugolix Combi...	18 Years - 50 Years	Sumitomo Pharma Switzerland GmbH
A Study to Evaluate Changes in Hair in Adult Participants Taking Oral Oriahnn Capsules With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF)	NCT06058728	Uterine Fibroid...		18 Years - 50 Years	AbbVie
A Phase 3B Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Women With Uterine Fibroids or Endometriosis	NCT05862272	Uterine Fibroid... Endometriosis	Relugolix Combi...	18 Years - 50 Years	Sumitomo Pharma Switzerland GmbH
A Study to Evaluate Changes in Hair in Adult Participants Taking Oral Oriahnn Capsules With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF)	NCT06058728	Uterine Fibroid...		18 Years - 50 Years	AbbVie
Hormone Replacement Therapy and the Risk of Breast Cancer Recurrence in Women With Previous Early Stage Breast Cancer	NCT00003771	Breast Cancer Menopausal Symp...	therapeutic est... norethindrone a...	-	National Cancer Institute (NCI)

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