CTRI/2025/01/078944 [Registered on: 17/01/2025] Trial Registered Prospectively
Last Modified On:
17/11/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
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
Scientific Title of Study
A Prospective, Randomized, Multi-Centre, Parallel-Group, Assessor-Blind, Active-Controlled,
Phase III Study to Assess the Efficacy and Safety of Fixed Dose Combination of Relugolix,
Estradiol, and Norethindrone Acetate in Comparison to Leuprolide in Heavy Menstrual
Bleeding Associated with leiomyomas (fibroids) in premenopausal women
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
VRL-CT-24-003, Version No: 3.0 dated 24-Jul-2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Avinash Andhale
Designation
Principal Investigator
Affiliation
Vivotech Research Private Limited
Address
Plot no D17 4 TTC Industrial Area Turbhe MIDC Navi Mumbai 400703 India
Thane MAHARASHTRA 400703 India
Phone
9987598349
Fax
Email
pi@vivotechresearch.com
Details of Contact Person Scientific Query
Name
Dr Avinash Andhale
Designation
Principal Investigator
Affiliation
Vivotech Research Private Limited
Address
Plot no D17 4 TTC Industrial Area Turbhe MIDC Navi Mumbai 400703 India
MAHARASHTRA 400703 India
Phone
9987598349
Fax
Email
pi@vivotechresearch.com
Details of Contact Person Public Query
Name
Badrinath Sangle
Designation
Director
Affiliation
Vivotech Research Private Limited
Address
Plot no D17 4 TTC Industrial Area Turbhe MIDC Navi Mumbai 400703 India
Thane MAHARASHTRA 400703 India
Phone
09930646601
Fax
Email
badrinath@vivotechresearch.com
Source of Monetary or Material Support
AKUMS DRUGS & PHARMACEUTICALS LTD First floor CT Dept Plot No.131 to 133, Block –C, Mangolpuri Industrial Area,
Phase-I (Adjoining CBSE Office),
Delhi -110083, India.
Primary Sponsor
Name
AKUMS DRUGS PHARMACEUTICALS LTD
Address
Clinical Trial Department Plot No 131 to 133 Block C Mangolpuri
Industrial Area Phase I adjoining CBSE Office Delhi 110083 India
Civil Hospital Building Basement, Gynac OPD No. 78, Belgavi Institute of Medical Sciences, Belgavi - 590001, Karnataka, India Belgaum KARNATAKA
9199642483
fallingstars07@gmail.com
Dr Neha Lad
Dr. Lads Navjeevan Hospital,
Dept of Gynaecology, First floor, Holkar Marg, Tidke Colony, Near Mahamarg bus stop, Nashik- 422003 Nashik MAHARASHTRA
9225100643
drnehanitin@gmail.com
Dr Asmita Patil
Dr. R. N. Cooper General Hospital and Medical College
Department of OBGY OPD E2, First floor, E Wing
Dr. R.N Cooper General Hospital & H.B.T Medical college, Bhaktivedanta Swami Marg Juhu Scheme, Juhu, Vile Parle West Mumbai - 400056 Mumbai (Suburban) MAHARASHTRA
9869831081
drasmi2001@gmail.com
Dr Nisha Chakravarti
GCS Medical College, Hospital and Research Centre
GCS Medical Collge, Hospital and Research Centre Dept of Gynaecology, G-18, Ground floor Opp. DRM Office, Near Chamunda Bridge, Naroda Road, Ahemdabad, Gujarat- 380026 Ahmadabad GUJARAT
9687600217
nishachakrvarti.gynec@gmail.com
Dr Divya Dwivedi
GSVM Medical College
Room No. 16, Ground Floor, Department of Gynaecology, GSVM Medical college Swaroop Nagar, Kanpur 208002, UP India Kanpur Nagar UTTAR PRADESH
9454558714
drdd2020@gmail.com
Dr Parmar Manali
Hira Mongi Navneet Hospital
Valaji Ladha Road, Mulund West, Mumbai City Maharashtra-400080 India. Mumbai (Suburban) MAHARASHTRA
9819350252
hospidoc@yahoo.com
Dr Ravindra Keshavrao Shelmohakar
Imperial Multispecialty Hospital
Ground floor, OPD No. 07, Gate No- 1193, Pingle Pride, Near Radha Swami Ashram, Chikhali, Pune- 411062. Pune MAHARASHTRA
9225634876
ravindrashelmohakar23@gmail.com
DrGourisankar Kamilya
IPGMER, SSKM Hospital
Department of Gynaecology and obstetrics, 2nd floor, Roland Ross Building IPGME & R and SSKM Hospital 244, A.J.C Bose Road Kolkata - 700020, West Bengal, India Kolkata WEST BENGAL
Kala Bagh, Ajmer-305001, Rajasthan Ajmer RAJASTHAN
7627026609
suchitanarayan.clinical@gmail.com
Dr Tushar Suvagiya
Jupiter Hospital and Research Centre,Vadodara
Jupiter hospital and Research Centre,First floor Dept of Gynaec, Opp. ICAI Bhavan Sun Pharma- Atladara road, Atladara, Vadodara-390013 Ahmadabad GUJARAT
9825064857
drtusharsuvagiyanm@gmail.com
Dr Aruna Verma
Lala Lajpat Rai Memorial Medical College
Dept of Obstructive & Gynaecology, LLRM Medical College, Garh Road, Meerut, Uttar Pradesh, India 250004 Meerut UTTAR PRADESH
9997706487
arunaverma36@gmail.com
Dr Sonia Agarwal
Maharaja Agrasen Hospital
West Punjab Bagh, New Delhi-110026 New Delhi DELHI
9999953018
dr.soniaagarwal.mah@gmail.com
Dr Manohar R
Mandya Institute of Medical Sciences
Gynaecology department, ground floor, Mandya Institute of Medical Sciences, Mandya MC Road Nehrunagar Madya, Karnataka - 571401 Mandya KARNATAKA
1st floor, OP Chamber, D.No. 43-9-201, Sy No. 321-323, Railway New Colony, Vishakhapatnam-530016, Andhra Pradesh, India Visakhapatnam ANDHRA PRADESH
9346627652
medigenehospital@yahoo.com
Dr Lakshmikantha G
Mysore Medical College & Research Institute
Clinical Research Department, K R Hospital, Irwin Road, Mysore- 570001 Gynaecology department, ground floor, Mysore Medical college and Research Institute, K R Hospital, Irwin Road, Mysore- 570002
Mysore KARNATAKA
9740810611
gdrlakshmikantha@gmail.com
Dr Ramila Jain
Nirogyam ICU and Multispecialty Hospital
201-204, 303-304 Nirgun One Complex, beside Orchid Exotica, near Makarba Underpass, Makarba, Ahmedabad-380051 Ahmadabad GUJARAT
9904628373
dr.ramilajain@gmail.com
Dr Ponkhshe Parth Aditya
Oyester & Pearl Hospital
1771-75, Ganeshkhind Road, Shivajinagar, Pune- 411005, Maharashtra, India Pune MAHARASHTRA
Dept of Gynaecology & Obstetrics, Jambe road, Near Khandoba Mnadir, Pune - 411033 Maharashtra, India Pune MAHARASHTRA
9521058844
punawalehospitalresearch@gmail.com
Dr Tulugu Sasikala
RIMS Govt. Medical College & Govt. General Hospital (Old RIMSGGH)
Department of Gynacology, OPD No. 07, Ground Floor, Govt. Medical College & Govt. General Hospital (Old RIMSGGH), Srikakulam-532001, Andhra Pradesh, India Srikakulam ANDHRA PRADESH
Uttar Pradesh University of Medical Sciences, Saifai, Etawah - 206130
First Floor, New OPD Building, Clinical Research Department, Room No. 40, Saifai Etawah, India - 206130 Etawah UTTAR PRADESH
Patients will receive FDC of Relugolix + Estradiol + Norethindrone Acetate (40 mg + 1 mg + 0.5 mg) tablet orally OD every day from Week 1 (Day 1) to Week 12 (Day 84)
Comparator Agent
Leuprolide acetate (3.75 mg) for injection
Patients will be administered Leuprolide (3.75 mg) depot injection IM once every 4 weeks i.e., (Day 1, Day 28 and Day 56).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
50.00 Year(s)
Gender
Female
Details
1. Premenopausal female aged 18 to 50 years old inclusive on the day of signing and dating the informed consent form. 2. Patient with regularly occurring menstrual periods of 3 to 14 days duration with a cycle interval of 21 to 35 days from the start of 1 menstrual period until the start of the next, by participant history for at least 3 months prior to the first screening visit. 3. Confirmed diagnosis of uterine fibroids that is supported by documented evidence either previous or at Screening of transvaginal and or transabdominal ultrasound or CT abdomen or MRI abdomen and have not received any surgical treatment for uterine fibroid and at least one measurable non-calcified myoma with a longest diameter of less than or equal to 3 cm at Screening visit. 4. Patient with heavy menstrual bleeding associated with uterine fibroids as evidenced by a PBAC score more than or equal to 100 which corresponds to MBL more than 80 mL in the previous menstrual cycle at Randomization visit 5. Women of childbearing potential WOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study. WOCBP must have a negative urine pregnancy test at screening or baseline visit. 6. Patient with ability to understand and provide written informed consent form, which must have been obtained prior to screening. Minimum Education 8th pass. 7. Patients willing to comply with the protocol requirements.
ExclusionCriteria
Details
1. 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
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Percentage of patients to achieve PBAC score
less than 75 over the last 28 days
Percentage of patients to achieve PBAC score
less than 75 over the last 28 days
Secondary Outcome
Outcome
TimePoints
Percentage of patients to achieve a 50 percent reduction of PBAC score
Baseline to Week 12
Percentage of patients to achieve amenorrhea
Baseline to Week 12
Time to achieve amenorrhea
Baseline to Week 12
Percentage change from baseline in PBAC score over the last 28 days
Baseline to Week 12
Percentage change from baseline in primary uterine fibroid volume
Baseline to Week 12
Target Sample Size
Total Sample Size="338" Sample Size from India="338" Final Enrollment numbers achieved (Total)= "338" Final Enrollment numbers achieved (India)="338"
Phase of Trial
Phase 3
Date of First Enrollment (India)
28/01/2025
Date of Study Completion (India)
15/09/2025
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Date Missing
Estimated Duration of Trial
Years="1" Months="6" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Completed
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a prospective, randomized, multicenter, parallel-group, assessor-blind, active-controlled Phase III study. The study will commence following regulatory and Ethics Committee (EC) approval. After confirming eligibility, patients will be randomized in a 1:1 ratio into either the test or comparator arm. Patients in the test arm will receive a fixed-dose combination of Relugolix + Estradiol + NETA (40 mg + 1 mg + 0.5 mg) orally once daily for 12 weeks, while those in the comparator arm will be administered leuprolide depot injection intramuscularly every 4 weeks for 12 weeks. The randomized patients will continue their assigned treatment for 12 weeks, with Week 12 marking the End of Treatment (EOT) visit. Assessments will be conducted as per the Schedule of Assessments. The study includes a total of six visits. Patients will be provided with a diary and PBAC chart to record details on study product intake/administration, concomitant medications, menstrual bleeding, rescue medication, and any adverse events. Patients are required to bring their completed diaries to each visit. Safety and efficacy will be evaluated throughout the study period.