Efficacy and Safety of Fixed Dose Combination of Relugolix, Estradiol, and Norethindrone Acetate in Comparison to Leuprolide in Heavy Menstrual Bleeding Associated With Uterine Fibroids

Recruitment & Eligibility

Status: ot Yet Recruiting

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1. Patient willing to provide written informed consent

2. Premenopausal female of age 18 – 50 years and BMI of 18 – 30 kg/m2

3. Regular menstrual periods of duration of 3 to 14 days and a cycle interval of 21 to 35 days (from the start of one menstrual period until the start of the next) for at least 3 months prior to Screening

4. Confirmed diagnosis of uterine fibroids that is supported by a documented evidence (either previous or at Screening) of ultrasound/CT abdomen/MRI abdomen and have not received any surgical treatment for uterine fibroid

5. Heavy menstrual bleeding associated with uterine fibroids

6. Women of childbearing potential must have a negative urine pregnancy test at Screening and at Randomization visit and not intend to become pregnant and agree to use 2 forms of non-hormonal contraceptive during the study

Exclusion Criteria

1. Patients with ultrasound (at screening) demonstrating pathology other than uterine fibroids that could be responsible for or contributing to the patients heavy menstrual bleeding

2. Patient has a rapidly enlarging uterine fibroid as per Investigator’s opinion and who is planning to undergo gynaecological surgery or ablation procedures for uterine fibroids during the study period.

3. Patients with history or current osteoporosis or other metabolic bone disorder.

4. Patients with history or current clinically significant hypocalcaemia, hypo- or hyperphosphatemia

5. Patients with history of the use of bisphosphonates, calcitonin, calcitriol, teriparatide, denosumab, or any medication other than calcium and vitamin D preparations to treat BMD loss

6. Patients with history or current thyroid disorders

7. Patients with history (documented) of blood disorders

8. Patients with history of allergic or hypersensitive reaction or intolerance to any of the ingredients of relugolix or estradiol or norethindrone acetate or leuprolide or its excipients, that will be used in the study

9. Patients with history of lower abdominal pain due to irritable bowel syndrome or inflammatory bowel disease or severe intestinal cystitis or chronic UTI

10. Patients with history or current or suspected carcinoma breast or any other estrogen-dependent neoplasia

11. Patients with history of malignancy

12. Patients with history of bilateral oophorectomy or hysterectomy

13. Patients with marked intermenstrual bleeding as per Investigators opinion

14. Patients taking contraindicated medications within the last 12 weeks prior to Randomization

15. Patients with uncontrolled hypertension at Screening and Randomization or hypotension at Screening and Randomization

16. Patients with QTcF greater than or equal to 440 milliseconds in 12-lead ECG or any other abnormal ECG findings at Screening and Randomization

17. Patients with a Hb level less than 8.0 g/dL at Screening and Randomization

18. Patients with inadequate hepatic function (total bilirubin greater than or equal to 1.5 X ULN or AST greater than or equal to 3 X ULN or ALT greater than or equal to 3 X ULN)

19. Patients with a history of stroke, thrombotic event, thyroid disorder, convulsion, psychiatric disorder, cardiovascular disease, gastrointestinal, hepatic, renal, pulmonary, auto-immune disease, any active infection, or any other clinically significant condition requiring treatment which at the Investigator’s discretion might interfere with the study

20. Patients who has tested positive for HIV, HBV or HCV at Screening

21. Patient is pregnant or breastfeeding or planning a pregnancy within the next 6 months or less than 6 months postpartum, post-abortion, or post-pregnancy at the time of Screening

22. Patients with history of smoking within the last 3 months prior to Screening

23. Patients with history of alcohol or drug abuse within the last 3 months prior to Screening

24. Patients who have participated in another Investigational study within the 3 months prior to Screening in this study

25. Investigator, study personnel, sponsor representatives and their first-degree relatives

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of patients to achieve PBAC score less than 75 over the last 28 daysTimepoint: Baseline to 12 weeks

Secondary Outcome Measures

Name	Time	Method
Percentage change from baseline in primary uterine fibroid volumeTimepoint: Baseline, 12 weeks;Percentage of patients experiencing vasomotor symptomsTimepoint: up to 12 weeks;Percentage of patients to achieve a 50 percentage reduction of PBAC score from BaselineTimepoint: Baseline, 12 weeks;Proportion of patients with AEsTimepoint: Screening to Week 16