“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 tosevere symptomatic uterine fibroids.
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 291
- Locations
- 11
- Primary Endpoint
- Change in fibroid volume before and after treatment/end of study
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Computer generated randomization
- Masking
- Open Label
Eligibility Criteria
- Ages
- 18.00 Year(s) to 40.00 Year(s) (—)
- Sex
- Female
Inclusion Criteria
- •Premenopausal woman between 18 to 40 years of age (both inclusive).
- •Subjects having uterine bleeding caused by fibroids.
- •Subjects having Body mass index (BMI) of 18 to
- •Subjects having uterine size equivalent to at least 10 weeks and no more than 16 weeks of gestation in a gravid uterus.
- •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.
- •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.
- •Subjects having myoma related anaemia (Blood haemoglobin <12 g/dL).
- •Subjects having clinical breast examination without significant findings at screening visit.
- •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.
- •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.
- •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.
Exclusion Criteria
- •Subjects with history of uterus surgery (except caesarean section or cervical conisation), endometrial ablation or uterine artery embolization.
- •Subjects with history of or current uterine, cervical, ovarian or breast cancer.
- •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.
- •Subjects having a condition requiring immediate blood transfusion or severe anaemia defined as blood haemoglobin level of <6 g/dL.
- •Subjects having a known hemoglobinopathy (i.e. Sickle cell anaemia and Thalassemia).
- •Subjects having known any coagulation disorder.
- •Subjects having concomitant adenomyosis.
- •Subjects having one or more ovarian cysts ≥ 4 cm in diameter diagnosed by transvaginal ultrasound.
- •Subjects with a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRHagonist.
- •Subjects taking treatments with progestins (systemic or progestin releasing intra-uterine system) or an oral contraceptive within one month prior to screening visit.
- •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.
- •Subjects taking systemic glucocorticoid treatments and/or systemic depot glucocorticoid treatments within one week or two months prior to screening visit, respectively.
- •Subjects with history of or known current osteoporosis.
- •Subjects with genital bleeding of unknown etiology or for reasons other than uterine fibroids.
- •Subjects with abnormal eGFR (< 60 mL/min/1.73 m2) will be excluded from the study.
- •Subjects with abnormal Liver Function Test with values more than 2.5 times the upper limit of normal.
- •Subjects with known case of Oncological Conditions.
- •Subjects with known case of HIV infection, hepatitis B, or hepatitis C Infection.
- •Subject with any clinically significant laboratory abnormalities at screening visit.
- •Suspected hypersensitivity to either of the study medications or any of the ingredients of the formulation.
- •Subjects with any other medical condition that might adversely impact the safety of the study participants or confound the study results.
- •Subjects who have been treated with an investigational drug or investigational device within a period of 4 weeks prior to study entry.
- •Currently taking prohibited concomitant medications(s) listed and inability/unwillingness to discontinue them for the entire study period.
- •Suspected inability or unwillingness to comply with the study procedures.
Outcomes
Primary Outcomes
Change in fibroid volume before and after treatment/end of study
Time Frame: Change in fibroid volume before and after treatment/end of study | (week 12)
(week 12)
Time Frame: Change in fibroid volume before and after treatment/end of study | (week 12)
Secondary Outcomes
- 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).)
- Reduction in menstrual blood loss after treatment/end of study (week 12) as assessed by(Pictorial blood loss assessment chart (PBAC) scores.)
- 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)