CTRI/2022/03/041372 [Registered on: 24/03/2022] Trial Registered Prospectively
Last Modified On:
09/12/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A Study of Mifepristone 10 mg and 25 mg tablets compared with Leuprolide acetate 3.75 mg injection in the preoperative treatment of moderate to severe uterine fibroids.
Scientific Title of Study
“A Phase III, Randomized, Open Label, Parallel Group, Active Controlled,
Comparative, Multicentric Clinical Study to Evaluate the Efficacy and Safety of Mifepristone 10 mg and 25 mg tablets compared with Leuprolide acetate 3.75 mg intramuscular injection in the preoperative treatment of moderate to
severe symptomatic uterine fibroids.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
BRPL/CT/MIFE/01/21, Version 2.0, Date 06.03.2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Aditi Datta
Designation
Managing Director
Affiliation
Biosite Research Private Limited
Address
Office No 81, 82, 83 & 84 3rd Floor Chandru Complex, 18th
Main RBI, Layout JP Nagar Phase 7, Bangalore
Bangalore KARNATAKA 560078 India
Phone
091-9811788955
Fax
Email
aditi.datta@biositeindia.com
Details of Contact Person Scientific Query
Name
Dr Aditi Datta
Designation
Managing Director
Affiliation
Biosite Research Private Limited
Address
Office No 81, 82, 83 & 84 3rd Floor Chandru Complex, 18th
Main RBI, Layout JP Nagar Phase 7, Bangalore
KARNATAKA 560078 India
Phone
091-9811788955
Fax
Email
aditi.datta@biositeindia.com
Details of Contact Person Public Query
Name
Dr Aditi Datta
Designation
Managing Director
Affiliation
Biosite Research Private Limited
Address
Office No 81, 82, 83 & 84 3rd Floor Chandru Complex, 18th
Main RBI, Layout JP Nagar Phase 7, Bangalore
KARNATAKA 560078 India
Phone
091-9811788955
Fax
Email
aditi.datta@biositeindia.com
Source of Monetary or Material Support
Akums Drugs Pharmaceuticals Limited,Plot No. 131 to 133, Block –C, Mangolpuri Industrial Area, Phase -1 (Adjoining CBSE Office), New Delhi-110083.
Primary Sponsor
Name
Akums Drugs Pharmaceuticals Limited
Address
Plot No. 131 to 133, Block –C, Mangolpuri Industrial Area, Phase-1 (Adjoining CBSE Office), New Delhi - 110083.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 11
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Mousumi Dutta
, Life Line Diagnostics center cum Nursing Home
Department of Gynecology & Obstetrics,4A, Wood Street, Kolkata-700016. Kolkata WEST BENGAL
9830424381
drmdms@gmail.com
Dr Manidip Pal
College of Medicine and JNM Hospital
Department of Gyanaecology, WBUHS, Kalyani - 741235
Nadia WEST BENGAL
9051678490
manideep2b@yahoo.com
Dr Ayesha Ahmed
Era’s Lucknow Medical College & Hospital
Department of Obstetrics and Gynecology, Sarfarazjganj Hardoi Road Lucknow- 226003 Lucknow UTTAR PRADESH
8800807090
docayeshaahmad@gmail.com
Dr Isukapalli Vani
Government of Medical College and Government General Hospital
Dept. of Gynaecology, Srikakulam- 532001 Srikakulam ANDHRA PRADESH
8942279033
drivaniggh@yahoo.com
Dr Shaily Agarwal
GSVM Medical College
Department of Gynecology, Swaroop
Nagar Kanpur-208002 Kanpur Nagar UTTAR PRADESH
9415368683
drspourush@gmail.com
Dr Rekha Sachan
King Georges medical University
Department of Obstetrics and Gynecologist, Chowk Lucknow, 226003 Lucknow UTTAR PRADESH
8765000700
drrekhasachan@gmail.com
Dr Nitin Suryakant Kshirsagar
Krishna Institute of Medical Sciences
Department of Gynecology, “Deemed to be university†Karad, Pune Bangalore Highway 4, Malkapur Road, karad Sangli MAHARASHTRA
9890942781
kshirsagarnitin793@gmail.com
Dr Manohar R
Mandya Institute of Medical Science
Department of OBG,
Mandya-571401 Mandya KARNATAKA
9886445854
drgkamilya@gmail.com
Dr Neelam Nalini
Rajendra Institute of Medical Sciences (RIMS)
Department of Obstetrician &
Gynaecologist, Bariatu, Ranchi-834009 Ranchi JHARKHAND
9334701303
jharkhand.obsgynae@gmail.com
Dr Dibyendu Banerjee
Sengupta Hospital Developers
Department of Gynecology, 4, Harimohan Dutta Road, DUM DUM, Kolkata- 700028 Kolkata WEST BENGAL
9830011037
drdban@yahoo.co.in
Dr Nidhi Chandil
Vidhya Hospital & Trauma Centre
Department of Gynecology, Harikansh Garhi, Raebareli Road, Mohanlalganj, Lucknow, INDIA 226301 Lucknow UTTAR PRADESH
The Recommended Dose is every 28 days, starting from day 1 to 5 of the menstrual cycle, for 12
weeks (total 3 injections).
Intervention
Mifepristone 10 mg Tablets
The Recommended Dose is one
tablet, once daily, orally, starting from day 1 to 3 of the menstrual cycle, for a period of 12 weeks.
Intervention
Mifepristone 25 mg Tablets
The Recommended Dose is one tablet, once daily, orally, starting from day 1 to 3 of the menstrual cycle, for a period of 12 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
40.00 Year(s)
Gender
Female
Details
1. Premenopausal woman between 18 to 40 years of age (both inclusive).
2. Subjects having uterine bleeding caused by fibroids.
3. Subjects having Body mass index (BMI) of 18 to 40.
4. Subjects having uterine size equivalent to at least 10 weeks and no more than 16 weeks of gestation in a gravid uterus.
5. Subjects having myomatous uterus with at least one uterine myoma of ≥ 3 cm diameter in size and no myoma larger than 10 cm diameter in size diagnosed by transvaginal ultrasound.
6. Subjects with the presence of one or more of the following symptoms: menorrhagia, dysmenorrhea, pelvic pressure, abdominal lump, dull aching lower abdominal pain, or dyspareunia.
7. Subjects having myoma related anaemia (Blood haemoglobin <12 g/dL).
8. Subjects having clinical breast examination without significant findings at screening visit.
9. Subjects of childbearing potential must be practicing conventional contraceptive methods such as sexual abstinence, barrier methods, diaphragms, condom or partner with a vasectomy, male or female
sterilization performed at least 6 months prior to screening and confirmed azoospermia.
10. Subjects who are able to understand and give voluntary, written informed consent to participate in this clinical investigation and from whom IEC/IRB approved written informed consent has been obtained.
11. Subjects shall be willing and able to understand and comply with the requirements of the study, administer the medication as instructed, return for the required treatment period visits, comply
with therapy prohibitions, and be able to complete the study.
ExclusionCriteria
Details
1. Subjects with history of uterus surgery (except caesarean section or cervical conisation), endometrial ablation or uterine artery embolization.
2. Subjects with history of or current uterine, cervical, ovarian or breast cancer.
3. Subjects with history of atypical hyperplasia or a current endometrium hyperplasia (atypical or non-atypical) or adenocarcinoma or similar lesions in the endometrial biopsy during screening visit or in a biopsy performed within the past 6 months.
4. Subjects having a condition requiring immediate blood transfusion or severe anaemia defined as blood haemoglobin level of <6 g/dL.
5. Subjects having a known hemoglobinopathy (i.e. Sickle cell anaemia and Thalassemia).
6. Subjects having known any coagulation disorder.
7. Patients using any other contraceptive method other than conventional methods.
8. Subjects having concomitant adenomyosis.
9. Subjects having a large uterine polyp (> 2 cm) diagnosed by transvaginal ultrasound.
10. Subjects having one or more ovarian cysts ≥ 4 cm in diameter diagnosed by transvaginal ultrasound.
11. Subjects with a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRHagonist.
12. Subjects taking treatments with progestins (systemic or progestin releasing intra-uterine system) or an oral contraceptive within one month prior to screening visit.
13. Subjects taking acetylsalicylic acid, mefenamic acid, anticoagulants such as cumarins and/or antifibrinolytic drugs such as tranexamic acid within one week prior to screening visit.
14. Subjects taking systemic glucocorticoid treatments and/or systemic depot glucocorticoid treatments within one week or two months prior
to screening visit, respectively.
15. Subjects with history of or known current osteoporosis.
16. Subjects with genital bleeding of unknown etiology or for reasons other than uterine fibroids.
17. Subjects with current history of severe asthma.
18. Subjects with abnormal eGFR (< 60 mL/min/1.73 m2) will be excluded from the study.
19. Subjects with abnormal Liver Function Test with values more than 2.5 times the upper limit of normal.
20. Subjects with known case of Oncological Conditions.
21. Subjects with known case of HIV infection, hepatitis B, or hepatitis C Infection.
22. Subject with any clinically significant laboratory abnormalities at screening visit.
23. Suspected hypersensitivity to either of the study medications or any of the ingredients of the formulation.
24. Subjects who are pregnant or lactating or planning to become pregnant during the study period.
25. Subjects with any other medical condition that might adversely impact the safety of the study participants or confound the study
results.
26. Subjects who consume abuse drugs, or have any condition that would compromise compliance with this protocol.
27. Subjects who have been treated with an investigational drug or investigational device within a period of 4 weeks prior to study entry.
28. Currently taking prohibited concomitant medications(s) listed and inability/unwillingness to discontinue them for the entire study period.
29. Suspected inability or unwillingness to comply with the study procedures.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Change in fibroid volume before and after treatment/end of study
(week 12)
Change in fibroid volume before and after treatment/end of study
(week 12)
Secondary Outcome
Outcome
TimePoints
Change in uterus volume before and after treatment/end of study (week 12).
Baseline, Week 12
Change in the Red blood cell count, Haemoglobin, and haematocrit before and after
treatment/end of study (week 12).
Baseline, Week 12
Reduction in menstrual blood loss after treatment/end of study (week 12) as assessed by
Pictorial blood loss assessment chart (PBAC) scores.
Baseline, Week 12
Proportion of subjects with amenorrhea at week 4, week 8 and end of study (week 12)
Baseline, Week 4, Week 8, Week 12
Improvement in symptoms including pelvic pain, lumbar pain, rectal pain, pelvic pressure,
dysmenorrhea, menorrhagia, metrorrhagia, dyspareunia, and non-menstrual abdominal pain
at week 4, week 8 and end of study (week 12)
Baseline, Week 4, Week 8, Week 12
Target Sample Size
Total Sample Size="291" Sample Size from India="291" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a "A Phase III, Randomized, Open Label, Parallel Group, Active Controlled, Comparative, Multicentric Clinical Study to Evaluate the Efficacy and Safety of Mifepristone 10 mg and 25 mg tablets compared with Leuprolide acetate 3.75 mg intramuscular injection in the preoperative treatment of moderate to severe symptomatic uterine fibroids."
After informed consent process, completion of all screening assessments and once all the inclusion/exclusion criteria are met, the eligible subjects shall be enrolled into the study. Demographics, and Medical and surgical history shall be recorded during screening visit. Physical examination (including general and systemic examinations), details of concomitant
medications and adverse events if any shall be done during screening and each successive visit. Vital signs (like pulse rate, blood pressure, respiratory rate and body temperature) shall be measured on each visit. 12 Lead ECG examination shall be performed during screening visit and end of study visit. Laboratory investigations including Complete blood count (CBC), Liver Function Test (LFT) (SGOT, SGPT, Total Serum Bilirubin), Renal Function Test (RFT) (BUN, Serum Creatinine), Estimated Glomerular Filtration Rate (eGFR), Serum ferritin, Cortisol,
Estradiol, and Follicle stimulating hormone (FSH), tr shall be performed during screening visit and end of study visit. Urine examination (Routine & Microscopic) and Urine pregnancy test for females of childbearing potential shall be performed during screening visit and end of study visit.
Transvaginal ultrasonography and Endometrial biopsy shall be performed during screening visit and end of study visit. Transabdominal ultrasonography at Screening, Visit 4 and End of Visit. Pictorial blood loss assessment charts (PBAC) shall be distributed to each patient and used to assess the blood loss during each visit. Each subject will be assessed for symptoms including pelvic pain, lumbar pain, rectal pain, pelvic pressure, dysmenorrhea, menorrhagia, metrorrhagia, dyspareunia, and non-menstrual abdominal pain. Inclusion and exclusion criteria shall be assessed during screening visit and confirmed randomization visit before enrolling the subject.
At randomization/baseline visit, all the eligible subjects shall be randomly assigned in 1:1:1 fashion to one of the three treatment groups. Study drug shall be dispensed by the independent dispenser or designated personnel at the investigative site who shall not participatein any other activity pertaining to subject’s safety and efficacy assessment that may impact the study outcome.