CTRI/2024/06/068615 [Registered on: 10/06/2024] Trial Registered Prospectively
Last Modified On:
14/02/2025
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-Center, 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 Uterine Fibroids
Trial Acronym
REEMEMBER
Secondary IDs if Any
Secondary ID
Identifier
ICR/23/001, Version No. 1.0; Dated 21/APR/2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Pravin Ghadge
Designation
AVP and Head_India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun house, Plot No. 201, B/1, Western Express Highway, Goregaon east.
Mumbai (Suburban)
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
pravin.ghadge@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Shruti Saha
Designation
Manager_Clinical Science_ Medical Affairs & Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun house, Plot No. 201, B/1, Western Express Highway, Goregaon east.
Mumbai (Suburban)
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
shruti.saha@sunpharma.com
Details of Contact Person Public Query
Name
Digambar Tornale
Designation
Senior Executive_India Clinical Research_Medical Affairs & Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun house, Plot No. 201, B/1, Western Express Highway, Goregaon east.
Mumbai (Suburban)
Mumbai (Suburban) MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
Digambar.Tornale@sunpharma.com
Source of Monetary or Material Support
Sun Pharmaceutical Industries Limited (SPIL),
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400 063, Maharashtra, India.
Primary Sponsor
Name
Sun Pharmaceutical Industries Limited (SPIL)
Address
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai 400 063, Maharashtra, India.
Abhayahasta Multispeciality
Hospital, 347/247, 2nd cross, In front of equerry cabin, Department of Genecology
Kaggadasapura Main Rd, C V Raman Nagar, Bengaluru, Karnataka 560093 Bangalore KARNATAKA
9740067232
cr@abhayahastahospital.com
Dr Sweety Saigal
Brij Medical Centre Pvt Ltd
Room no 3 Department of Gynecology 94-E Near Panki Police Station Panki Kanpur UP 208020 Kanpur Nagar UTTAR PRADESH
Floor No. 6, Clinical
research Department, Plot
No. 121, Zone no. , 04,
Dahanukar Colony,
Kothrud, Pune-411038,
Maharashtra Pune MAHARASHTRA
9881069693
drswapnalimaye1@gmail.com
Dr Dinesh Kansal
Dr B. L Kapur Memorial Hospital
Obstetrics & Gynecology and Laparoscopic Surgery Unit 1, Room no 50 Ground Floor, BLK-Max Centre For Women Health ,Dr B. L Kapur Memorial
Hospital, Pusa road, New Delhi-110005, India. Central DELHI
9810884822
Drdineshkansal@gmail.com
Dr Nitin Sutariya
Global Hospital
Consultant room no 2, Global Hospital, 4th floor Global Point, Nr Navjivan restaurant, sarthana Jakat Naka, Surat, Gujarat 395006 Surat GUJARAT
9099014100
sutariyawomenhospital@gmail.com
Dr Tulugu Sasikala
Government Medical College & Government General Hospital
Government Medical College
& Government General
Hospital (Old RIMSGGH), Srikakulam-532001, Andhra Pradesh. Srikakulam ANDHRA PRADESH
9573405562
drsasikala@gmail.com
Dr Neena Gupta
GSVM Medical College
Room No. 3, Ground Floor, Department of Gynaecology, Swaroop Nagar, Kanpur-208002, UP, India. Kanpur Nagar UTTAR PRADESH
9415131422
drneenagupta.research@gmail.com
Dr Parmar Manali Indrakumar
Hira Mongi Navneet Hospital
Ground floor, OPD no. 10, Department of Gynaecologist, Shree Pragati Foundation’s Hira Mongi Navneet Hospital, Valji Ladha Road, Near Kalidas Natya Gruh, Mulund West, Mumbai-400080, Maharashtra,India Mumbai (Suburban) MAHARASHTRA
9427058419
hospidoc@yahoo.com
Dr Gaurisankar Kamilya
IPGME&R and SSKM Hospital
Department of Gynaecology
and Obstetrics, 244, AJC
Bose Road, Bhowanipore,
Kolkata-700020, West Bengal Kolkata WEST BENGAL
9433122643
drgkamilya@gmail.com
Dr Kamlesh Kumari
Jaipur National University Institute for Medical Sciences and Research Centre
Department of
obstetrics and Gynecology,
Agra-Jaipur Road, Near
New RTO Office, Jagatpura,
Jaipur-302017, Rajasthan
India Jaipur RAJASTHAN
7221076311
drkamleshkumari@jnujaipur.ac.in
Dr Suchitra Narayan
Jawahar Lal Nehru Medical College
Jawahar Lal Nehru Medical
College, Department of Gynaecology Kala Bagh, Ajmer305001, Rajasthan, India Ajmer RAJASTHAN
76270-26609
Suchitanarayan.clinical@gmail.com
Dr Isukapalli Vani
King George Hospital
Department of Gynecology
Maharanipeta,
Visakhapatnam-530002,
Andhra Pradesh. Visakhapatnam ANDHRA PRADESH
9346627652
drivaniresearch@gmail.com
Dr Veena Gupta
Maharaja Agrasen Hospital
Room No 12, Ground Floor, Department of Genecology,
Maharaja Agrasen Hospital,
West Punjabi Bagh, New
Delhi- 110026 New Delhi DELHI
9811148465
veenakohat@gmail.com
Dr Madhavender Jain
Maharaja Agrasen Superspeciality Hospital
Department of Gynaecology Maharaja Agrasen Superspeciality
Hospital, Sector No 7, Central
Spine, Vidyadhar Nagar,
Jaipur, Rajasthan – 302039 Jaipur RAJASTHAN
9413062961
madhavenderjain2@gmail.com
Dr Aruna Subha Shree Rao
Maharani Ghosha Hospital, Government Medical College,
Department of Gynecology, Near Ambati Satram Area, Vizianagaram- 535003, Andhra Pradesh, India Vizianagaram ANDHRA PRADESH
9866655515
drarunaresearch@gmail.com
Dr P Malathi
Modern Government Maternity Hospital
Dept of obstetrics & Gynecology, Petlaburj, Hyderabad, T.S India. Hyderabad TELANGANA
9949362504
malathiponnuru@gmail.com
Dr Anuja Bhalerao
NKP Salve Institute of Medical Science and Research Centre & Lata Mangeshkar Hospital
Departments of Obstetrics &
Gynaecologist, NKP Salve Institute of Medical Science and Research Centre & Lata
Mangeshkar Hospital Hingna Road, Digdoh Hill, Nagpur Maharashtra-440019 Nagpur MAHARASHTRA
9823680572
anujabhalerao@yahoo.com
Dr Shalini Srivastava
OM Surgical Centre & Maternity Home
Room No. 203, Department
of Gynaecology, SA-17/3,
P-4, Sri Krishna Nagar,
Paharia, Ghazipur Road, Varanasi-221007, Uttar
Pradesh
Varanasi UTTAR PRADESH
9125679980
drshalinivns@gmail.com
Dr Patel Jaldhara Sukhlalbhai
Pagarav Hospital & ICU
Room No 4, First floor, Gynec Department Pagarav Hospital & ICU,
Sector-23,Nr. G-6, Circle, Opp.SBI ,Gandhinagar382023 Gujrat, India. Gandhinagar GUJARAT
9898257417
drjaldhara@gmail.com
Dr Jasani Krupali Babubhai
PHC-Prajna Healthcare
Consulting Room, PHC-Prajna Healthcare, 2nd Floor, 205-208, Aagam Avenue, Near Adani Gas Pump, Opp. Motera BRTS Stop, Sabarmati-380005 Ahmadabad GUJARAT
9662587399
krupalijasani04@gmail.com
Dr Vidya V Bhat
Radhakrishna Multispecialty Hospital and IVF Centre
Department of Gynaecology, Ground floor, Consultation room, Radhakrishna
Multispecialty Hospital and IVF Centre 3-4 Sunrise Tower, J P Road, Opp. Canara Bank,
Girinagar, Bangalore-560085 Bangalore KARNATAKA
9880128666
drvidyavbhat.research@gmail.com
Dr Deepa Chaudhary
SMS Hospital
Research Room, basement, Mahila chikitsalaya, Sanganeri Gate, Jaipur-302004. Jaipur RAJASTHAN
9413843022
deepagaurav35@gmail.com
Dr Mrinal Kanti Dash
Sparsh Hospital & Critical Care Pvt.Ltd
Department of gynaecology, room no 7, Basement, Sparsh Hospital & Critical
Care Pvt.Ltd. A/407, Sahid Nagar, Bhubaneswar, Odisha 751007 Odia. Khordha ORISSA
9437960744
mkdash8@gmail.com
Dr Mishra Abhipsa
Utkal Healthcare Pvt Ltd.
Department of Gynecology, OPD Room Ground Floor, Plot No-C/3,Niladri Vihar, Chandrasekharpur, Bhubaneswar, Orissa- 751021 India. Khordha ORISSA
6372196146
dramgyn@yahoo.co.in
Dr Dipti K Yadav
Venkateshwar Hospital
Room No 1110, first sloor, old building, department of genecology Venkateshwar Hospital SECTOR 18A Dwarka Delhi, India 110075. South West DELHI
9717939339
drdiptikumar@yahoo.co.uk
Dr Patel Raxit Mahendrakumar
VS General Hospital
Room no. 1, First Floor, Gynaec Ward, Trauma Building, VS General Hospital, Near Ellisbridge, Paldi, Ahmedabad- 380006 Ahmadabad GUJARAT
Patients will receive FDC of Relugolix + Estradiol + Norethindrone Acetate (NETA) (40 mg + 1 mg + 0.5 mg) tablet orally OD every day from Week 1 (Day 1) to Week 12 (Day 84).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
50.00 Year(s)
Gender
Female
Details
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
ExclusionCriteria
Details
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
Method of Generating Random Sequence
Stratified block 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
Baseline to 12 weeks
Secondary Outcome
Outcome
TimePoints
Percentage of patients to achieve a 50 percentage reduction of PBAC score from Baseline
Baseline, 12 weeks
Percentage change from baseline in primary uterine fibroid volume
Baseline, 12 weeks
Proportion of patients with AEs
Screening to Week 16
Percentage of patients experiencing vasomotor symptoms
up to 12 weeks
Target Sample Size
Total Sample Size="338" Sample Size from India="338" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
18/06/2024
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="6" Days="0"
Recruitment Status of Trial (Global)
Not Yet Recruiting
Recruitment Status of Trial (India)
Not Yet Recruiting
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, multi-center, parallel-group, assessor-blind, active-controlled, phase III study. The study will be initiated only after the receipt of regulatory and EC approval.
After confirming the eligibility, patients will be randomized in 1:1 ratio in either test arm or comparator arm. Patients in test arm will receive FDC of Relugolix + Estradiol + NETA (40 mg + 1 mg + 0.5 mg) once daily orally for 12 weeks, while patients in comparator arm will be administered leuprolide depot injection intramuscularly once every 4 weeks till 12 weeks. The randomized patients will take the allotted study medication for 12 weeks (Treatment period) and Week 12 will be considered EOT visit. During the study, assessments will be performed as mentioned in Schedule of Assessment.
The study consists of total six visits. Patients will be provided with diary and PBAC chart to record details about study product intake/administration, concomitant medication, menstrual bleeding details, any rescue medication taken, and adverse events. Patients will be required to bring completed diary at each visit. The safety and efficacy will be assessed during the study period.