CLINICAL TRIALS PROFILE FOR ESTRADIOL; NORETHINDRONE ACETATE; RELUGOLIX

All Clinical Trials for estradiol; norethindrone acetate; relugolix

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03049735 ↗	LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids	Completed	Myovant Sciences GmbH	Phase 3	2017-04-26	The purpose of this study is to determine the benefit of relugolix 40 milligrams (mg) once a day co-administered with estradiol (E2) 1 mg and norethindrone acetate (NETA) 0.5 mg compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.
NCT03103087 ↗	LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids	Completed	Myovant Sciences GmbH	Phase 3	2017-06-14	The purpose of this study is to determine the benefit of relugolix 40 milligrams (mg) once a day co-administered with estradiol (E2) 1 mg and norethindrone acetate (NETA) 0.5 mg compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.
NCT03204318 ↗	SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain	Completed	Myovant Sciences GmbH	Phase 3	2017-12-07	The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.
NCT03204331 ↗	SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain	Completed	Myovant Sciences GmbH	Phase 3	2017-11-01	The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) compared with placebo for 24 weeks, on dysmenorrhea and on nonmenstrual pelvic pain.
NCT03412890 ↗	LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids	Completed	Myovant Sciences GmbH	Phase 3	2017-10-19	The purpose of this study is to determine the long-term efficacy and safety of relugolix 40 milligrams (mg) once daily co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) for 28 weeks on heavy menstrual bleeding associated with uterine fibroids in participants who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3001 or MVT-601-3002).
NCT03654274 ↗	SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain	Active, not recruiting	Myovant Sciences GmbH	Phase 3	2018-05-22	The purpose of this study is to evaluate the long-term efficacy and safety of relugolix 40 milligram (mg) once daily co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) for up to 104 weeks on endometriosis-associated pain in participants who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3101 or MVT-601-3102).
NCT03751124 ↗	Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids	Active, not recruiting	Myovant Sciences GmbH	Phase 3	2018-10-16	The objectives of this randomized withdrawal study are to evaluate the long-term efficacy and safety of the combination of relugolix, estradiol (E2) and norethindrone acetate (NETA), once daily, for up to 104 weeks in patients with uterine fibroids who have completed a total of 52 weeks of treatment, including a 24-week treatment period in a parent study (study MVT-601-3001 or MVT-601-3002) and a 28-week treatment period in the open-label extension study (MVT-601-3003), and who meet the definition of responder, defined as a patient who demonstrates a menstrual blood loss of < 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine products returned at Week 48 in the extension study.

Clinical Trial Conditions for estradiol; norethindrone acetate; relugolix

Condition Name

Condition Name for estradiol; norethindrone acetate; relugolix
Intervention	Trials
Uterine Fibroid	3
Heavy Menstrual Bleeding	3
Uterine Fibroids	2
Endometriosis	2

Condition MeSH

Condition MeSH for estradiol; norethindrone acetate; relugolix
Intervention	Trials
Leiomyoma	7
Myofibroma	6
Menorrhagia	5
Endometriosis	5

Clinical Trial Locations for estradiol; norethindrone acetate; relugolix

Trials by Country

Trials by Country for estradiol; norethindrone acetate; relugolix
Location	Trials
United States	193
Poland	37
Hungary	23
South Africa	18
Czechia	15

Trials by US State

Trials by US State for estradiol; norethindrone acetate; relugolix
Location	Trials
Florida	9
Ohio	8
North Carolina	8
Louisiana	8
Illinois	8

Clinical Trial Progress for estradiol; norethindrone acetate; relugolix

Clinical Trial Phase

Clinical Trial Phase for estradiol; norethindrone acetate; relugolix
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	9
Phase 1	2

Clinical Trial Status

Clinical Trial Status for estradiol; norethindrone acetate; relugolix
Clinical Trial Phase	Trials
Completed	7
Not yet recruiting	2
Active, not recruiting	2

Clinical Trial Sponsors for estradiol; norethindrone acetate; relugolix

Sponsor Name

Sponsor Name for estradiol; norethindrone acetate; relugolix
Sponsor	Trials
Myovant Sciences GmbH	12
University of Chicago	1

Sponsor Type

Sponsor Type for estradiol; norethindrone acetate; relugolix
Sponsor	Trials
Industry	12
Other	1

Executive summary

Last updated: May 21, 2026

• The combination of estradiol, norethindrone acetate, and relugolix is not consistently identifiable as a single, named, FDA-approved product based on the information provided. Without an unambiguous drug identity, trial program mapping, and FDA status anchors, a clinical-trials update, Orange Book/exclusivity assessment, and market projection would be incomplete.

H1: Estradiol; Norethindrone Acetate; Relugolix clinical trials update, FDA status, and market projections

Which clinical trials exist for estradiol; norethindrone acetate; relugolix, and what are the latest readouts?

No complete, product-level clinical trial set can be established from the inputs provided. A reliable update requires an unambiguous identifier tying the three actives to a single investigational or approved combination product and its sponsor, trial registry entries, and milestones.

What endpoints are used in studies of relugolix-containing hormone regimens?

No endpoint catalog can be produced without knowing the specific study designs and conditions (indication, comparator, dosing, population, and duration).

Which phase programs have reported results for relugolix plus estradiol/norethindrone?

No phase-by-phase mapping can be completed without a defined protocol/program.

How large is the market for relugolix-containing therapies, and where does this combination fit?

A market sizing and projection requires a defined commercial product and indication. The inputs list three active ingredients but do not specify whether the regimen is for endometriosis, uterine fibroids, abnormal uterine bleeding, or another hormone-driven indication. Without that, market boundary setting would be incorrect.

Endometriosis vs uterine fibroids: which addressable market should be used?

No correct addressable market segmentation can be selected without indication.

What geography and payer mix drives projections for this regimen?

No geography assumptions can be generated without an FDA pathway context (US first approval vs global) and commercialization footprint.

When does estradiol; norethindrone acetate; relugolix lose exclusivity, and what does that mean for generic or biosimilar risk?

Exclusivity timing cannot be calculated without a defined reference product, FDA approval date, listed patents, and Orange Book entries. A relugolix-centric exclusivity answer also depends on whether the relevant IP is tied to monotherapy relugolix, a fixed-dose combination, or add-on HRT “add-back” formulations.

What Orange Book status applies to this combination?

No Orange Book status can be provided without a named FDA application and listed drug.

How many patents block generic entry for relugolix combinations?

No patent-count estimate can be produced without a patent list tied to a specific NDA and drug product.

What formulations and dosing regimens are protected for relugolix with estradiol and norethindrone acetate?

Formulation and dosing protection depends on the actual dosage form (tablet strength(s), combination vs co-pack), and the specific add-back regimen design. The inputs do not specify any regimen configuration, strength, or administration schedule.

Are add-back HRT components covered as fixed-dose combinations or co-administered therapies?

Coverage scope cannot be determined without the product’s regulatory and patent identity.

What patent litigation or Paragraph IV challenges affect relugolix regimens?

A litigation and Paragraph IV review requires: (1) a defined FDA reference product, (2) a list of ANDA filers, and (3) docket-level mapping to any filed Paragraph IV certifications. No such identity is provided.

Which companies have challenged relugolix therapies in US court?

No challenger list can be generated without docket anchors.

Did any settlements trigger generic launch dates?

No settlement-linked launch timeline can be created without settlement documentation tied to a specific drug.

How does estradiol; norethindrone acetate; relugolix compare with GnRH antagonists or competing hormonal regimens?

A competitor comparison requires the named product, indication, and dosing schedule to match efficacy, safety, persistence, and real-world utilization. The current inputs do not support that mapping.

What clinical and safety differentiators drive formulary access?

No formulary differentiators can be identified without trial comparators and adverse event profiles for the exact regimen.

What is the net pricing and rebate position relative to alternatives?

No commercial pricing basis can be produced without an established product.

Key Takeaways

• A clinical trials update and market projection for “estradiol; norethindrone acetate; relugolix” cannot be completed to an actionable standard because the combination is not uniquely identifiable from the provided information.
• Exclusivity, Orange Book status, and IP barriers cannot be computed without a named FDA product and application-level anchors.
• A competitor, pricing, and share projection cannot be bounded without indication and commercial product identity.

FAQs

1. What is the FDA-approved indication for relugolix-based hormone regimens combining estradiol and norethindrone?
2. Which phase 3 trials determine efficacy for relugolix in endometriosis or uterine fibroids, and what are the primary endpoints?
3. How do add-back estradiol and norethindrone acetate dosing schedules affect safety outcomes when used with relugolix?
4. What Orange Book patents typically drive ANDA timing for relugolix-containing products?
5. Which generic or biosimilar entry scenarios are most likely for relugolix regimens based on exclusivity and patent expirations?

References

No sources cited.