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Estradiol/norethindrone

Phase 3

Endometriosis | Small molecule | Endocrine |Roivant Sciences Ltd.|Last Updated: Jun 25, 2024

Success Probability

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Trial Design

UNCONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment802

FDA Designations

No designations recorded

Clinical trial landscape

Estradiol/norethindrone · 7 trials · 6 indications

Phase 3 7
NCT03751124Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine FibroidsUterine Leiomyoma
COMPLETED229 Analytics
NCT03654274SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated PainEndometriosis
COMPLETED802 Analytics
NCT03204318SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated PainEndometriosis Related Pain
COMPLETED638 Analytics
NCT03204331SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated PainEndometriosis Related Pain
COMPLETED623 Analytics
NCT03412890LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine FibroidsHeavy Menstrual Bleeding
COMPLETED477 Analytics
NCT03103087LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine FibroidsHeavy Menstrual Bleeding
COMPLETED382 Analytics
NCT03049735LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine FibroidsHeavy Menstrual Bleeding
COMPLETED388 Analytics
PHASE3COMPLETED
Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Uterine LeiomyomaUnlock trial analytics
PHASE3COMPLETED
SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain
EndometriosisUnlock trial analytics
PHASE3COMPLETED
SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
Endometriosis Related PainUnlock trial analytics
PHASE3COMPLETED
SPIRIT 2: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain
Endometriosis Related PainUnlock trial analytics
PHASE3COMPLETED
LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Heavy Menstrual BleedingUnlock trial analytics
PHASE3COMPLETED
LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Heavy Menstrual BleedingUnlock trial analytics
PHASE3COMPLETED
LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Heavy Menstrual BleedingUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period
Week 52/Baseline up to Week 76

MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. The sustained responder rate was calculated as the Kaplan-Meier estimate of the cumulative probability of MBL volume \< 80 mL through Week 76 using the Kaplan-Meier method.

Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 52
Week 52

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 52 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 52
Week 52

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 52 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 52 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 104
Week 104

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for dysmenorrhea declined from baseline to Week 104 by at least 2.8 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Percentage Of Participants Who Meet The NMPP Responder Criteria At Week 104
Week 104

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. A participant was defined as a responder if the NRS score for NMPP declined from baseline to Week 104 by at least 2.1 points without increased use of protocol-specified analgesics for pelvic pain at Week 104 relative to baseline. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine.

Percentage Of Participants Who Meet The Dysmenorrhea Responder Criteria At Week 24 Or End Of Treatment (EOT)
Week 24 or EOT

Assessed using a Numerical Rating Scale (NRS) score (11-point scale) for pain recorded daily in an electronic diary (e-Diary). The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.

Percentage Of Participants Who Meet The Non-Menstrual Pelvic Pain (NMPP) Responder Criteria At Week 24 Or EOT
Week 24 or EOT

Assessed using an NRS score (11-point scale) for pain recorded daily in an e-Diary. The criteria for a responder was based on a pre-defined threshold and accounted for analgesic use.

Percentage Of Participants Who Achieved Or Maintained An MBL Volume Of <80 Milliliters (mL) And At Least A 50% Reduction From Baseline MBL Volume At Week 52/End Of Treatment
Week 52/End of Treatment

A responder was a participant who had MBL volume of \< 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 52). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 52/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented.

Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA
From Baseline up to the last 35 days of treatment (up to Week 24)

A responder was a participant who had MBL volume of \< 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 24). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 24/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented. As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

Secondary Endpoints

Time To MBL Volume ≥80 mL During The Randomized Treatment Period
From Week 52/Baseline through Week 104
Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period
Week 52/Baseline up to Week 104
Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period
Week 76
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Relugolix plus E2/NETAEXPERIMENTALRelugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 52 weeks.
Placebo tablets and capsulesPLACEBO_COMPARATOR* Placebo for relugolix co-administered with placebo for E2/NETA for up to 52 weeks or until heavy menstrual bleeding returns. * Retreatment with open-label relugolix with E2/NETA will be offered if heavy menstrual bleeding returns.
Relugolix plus E2/NETA (Group A)EXPERIMENTALRelugolix co-administered with E2/NETA for 24 weeks.
Relugolix plus Delayed E2/NETA (Group B)EXPERIMENTALRelugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.
Placebo (Group C)PLACEBO_COMPARATORRelugolix placebo co-administered with E2/NETA placebo for 24 weeks.

Interventions

NameTypeDescription
RelugolixDRUGRelugolix 40 mg tablet administered orally once daily
Estradiol/norethindrone acetateDRUGCapsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily
Placebo for relugolixDRUGPlacebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor
Placebo for E2/NETADRUGPlacebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor
Estradiol/norethindrone acetate placeboDRUGE2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor.
Relugolix placeboDRUGRelugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.
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Eligibility Criteria

Age Range18 Years to 51 Years
SexFEMALE
Healthy VolunteersNo
Study Sites104

Inclusion Criteria: 1. Completed the open-label extension study (MVT-601-3003). 2. Is a responder: Has a menstrual blood loss of \< 80 mL AND at least a 50% reduction from the parent study Baseline based on the results of the alkaline hematin testing performed on the feminine products returned at t...

Countries:United StatesBrazilChileCzechiaHungaryItalyPolandSouth AfricaArgentinaAustraliaBelgiumBulgariaCanadaFinlandGeorgiaNew ZealandPortugalRomaniaSpainUkraineSwedenUnited Kingdom
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Frequently asked questions about Estradiol/norethindrone

What is Estradiol/norethindrone used for?

Estradiol/norethindrone is an investigational combination being studied for endometriosis related pain, heavy menstrual bleeding, uterine leiomyoma, and endometriosis. It is in Phase 3 clinical development as a small molecule therapy for these endocrine-related conditions in women.

Who makes Estradiol/norethindrone?

Estradiol/norethindrone is being developed by Roivant Sciences Ltd., a biopharmaceutical company traded on the NASDAQ under the ticker ROIV. The company is conducting Phase 3 clinical trials to evaluate this combination therapy for gynecological conditions.

What phase is Estradiol/norethindrone in?

Estradiol/norethindrone is in Phase 3 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities. The Phase 3 trials have been completed, with three studies enrolling a total of 1,261 women.

What clinical trials is Estradiol/norethindrone in?

Estradiol/norethindrone has been studied in three completed Phase 3 trials: NCT03103087 (LIBERTY 2) for heavy menstrual bleeding with uterine fibroids, NCT03204318 (SPIRIT 1) for endometriosis-associated pain, and NCT03204331 (SPIRIT 2) for endometriosis-associated pain. A fourth trial, NCT03751124, also studied the combination in uterine fibroids.

Is Estradiol/norethindrone the same as relugolix?

Estradiol/norethindrone is a component of combination therapy studied alongside relugolix. The clinical trials listed for Estradiol/norethindrone include studies of relugolix combined with estradiol and norethindrone acetate, such as NCT03751124. The drug is not the same as relugolix alone.