endometriosis in reproductive-age MedDRA version: 20.0 Level: PT Classification code 10014778 Term: Endometriosis System Organ Class: 10038604 - Reproductive system and breast disorders
Conditions
Interventions
Product Name: Mifepristone 2.5 mg tablets
Product Code: Mifepristone 2.5 mg tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: MIFEPRISTONE
CAS Number: 84371-65-3
Current Sponsor code: NA
Other
Sponsors
Litaphar Laboratorios
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Premenopausal female, between 18 and 45 years of age inclusive, at the time of signing consent [2] Patients with Endometriosis Associated Pelvic Pain (EAPP: i.e. any type of pelvic pain associated with endometriosis: non-menstrual pelvic pain, dysmenorrhea, dyschezia and dyspareunia) as measured by Visual Analogue Scale (VAS) = 40 mm at least once in the previous 4 weeks from baseline visit [3] patients with a history of EAPP for at least the past 6 months prior to the initial screening visit [4] Endometriosis diagnosed by laparoscopy and/or surgery in the past 10 years or less or diagnosed by MRI or transvaginal ultrasound in the past 5 years [5] Patients with a history of regular menstrual cycles (21-35 days) while not being on any pharmacological treatment that could alter the menstrual cycle (e.g. oral contraceptive pills) [6] Patients who agree to use only ibuprofen 400 mg as rescue medication up to a total daily dose of not more than 2400 mg [7] Patients willing and able (e.g. mental and physical condition) to participate in all aspects of the study as evidenced by providing signed written informed consent [8] Patient agrees to use double barrier contraception birth control methods (e.g. condom with spermicide) during the entire length of participation in the study. Patient is not required to use double barrier contraception methods if: - Sexual partner(s) is (are) vasectomized, at least 6 months prior to screening - Patient has had a bilateral tubal occlusion (including ligation and blockage methods such as Essure®), at least 3 months prior to screening - Patient is not sexually active with men; periodic sexual relationship(s) with men requires the use of dual non-hormonal contraception as noted above. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 220 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: [1] History of hypersensitivity or intolerance to the active substance or any of the excipients of the study medication [2] Subject is pregnant or breast-feeding or is planning a pregnancy within the duration of the study or is less than 6 months postpartum, post-abortion, or post-lactation at the time of entry into the screening period [3] Previous use of hormonal agents before the Screening visit: =24 weeks for GnRH agonists; =12 weeks for depot progestogens and danazol: =6 weeks for oral contraceptives [4] Patients with history of any cancer (including breast cancer) and/or histological diagnosis of endometrial atypical hyperplasia at baseline (note: the combination of endometrial thickness 180 mmHg or > 95 mmHg, respectively [14] Subject with hereditary porphyria [15] Abnormal laboratory findings considered by the investigator as clinically significant [16] Positive results for HBs-Ag, anti-HCV and HIV-1/HIV-2-antibodies [17] Use of drugs that could be expected to affect the release of sex hormones (e.g., antipsychotics); hypericum and CYP3A4 inductors (carbamazepine, phenobarbital, phenytoin, primidone, rifampicin) or inhibitors (such as cyclosporine, macrolide antibiotics, nefazodone, azolic antifungal agents and HIV protease inhibitors) [18] Intake of any analgesics other than ibuprofen: both opioids and non-steroidal anti-inflammatory drugs as well as paracetamol or metamizole during the screening period [19] History of drug or alcohol abuse within 6 months prior to screening [20] Participation in another trial within 3 months from the screening visit date; [21] Previous enrolment in this study [22] Any condition that, in the judgment of the investigator, may interfere with adherence to study procedures or study assessments [23] Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study [24] Unreliability or lack of cooperation during the screening period (Note that this includes proven ability to use the e-diaries via the internet).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show superiority of at least one dose of mifepristone 2.5 mg and mifepristone 5 mg relative to placebo for the treatment of endometriosis in reproductive-age women at 24 weeks in terms of the reduction of Endometriosis Associated Pelvic Pain (EAPP) as measured by Visual Analog Scale (VAS) and considering intake of rescue medication.;Secondary Objective: • Efficacy of mifepristone 2.5 mg & 5 mg during the 1st cycle and during the 2nd cycle in terms of the reduction of EAPP measured by VAS with the intake of rescue medication • Efficacy of mifepristone 2.5 mg & 5 mg vs. placebo during the 1st treatment cycle of the reduction of each type of pain (non-menstrual pelvic pain, dysmenorrhea and/or dyschezia and/or dyspareunia) • Percentage of responders based on the reduction in EAPP as measured by VAS with no intake of rescue medication • Effect of mifepristone 2.5 mg, 5 mg & placebo by the modified Biberoglu & Behrman pain scale, by the Patient Global Impression of Change scale and the Clinical Global Impressions scale, on “Quality of Life” assessed by the SF-36 Health Survey questionnaire, on fertility by the Hoogland score • Return to fertility after the treatment with mifepristone 2.5 mg & 5 mg for two cycles by the Hoogland score • Safety of mifepristone 2.5 mg & 5 mg during two treatment cycles and in comparison to placebo ;Primary end point(s): Co-Primary end points: - Pre-post absolute change between baseline and final value after 24 weeks double-blind treatment in EAPP - Final value at the end of 24 weeks of double-blind treatment in the amount of analgesic rescue medication (ibuprofen 400 mg tablets) ;Timepoint(s) of evaluation of this end point: - Pre-post absolute change between baseline and final value after 24 weeks double-blind treatment in EAPP - Final value at the end of 24 weeks of double-blind treatment in the amount of analgesic rescue medication (ibuprofen 400 mg tablets) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Pre-post absolute change for every 4 weeks of treatment in EAPP as documented on a VAS (in mm) throughout the trial by the patient in her diary - Intake of analgesic rescue medication for each 4-week period throughout the trial (i.e., number of pills/day) as documented by patient in her diary - Pre-post absolute change of each pain type associated with endometriosis (non-menstrual pelvic pain, dysmenorrhea, dyschezia and dyspareunia) as documented on a VAS (in mm) at each visit - Proportion of patients responding to treatment based on change in VAS EAPP and intake of analgesic rescue medication after 12 and 24 weeks of double-blind treatment - Pre-post absolute change in the total symptom and sign severity score calculated from the modified Biberoglu and Behrman scale - Clinical Global Impressions (CGI) scale at Week 24 of the 1st treatment cycle and Week 24 of the 2nd and 3rd treatment cycle - Patient Global Impression of Change (PGIC) scale at Week 24 of the 1st treatment cycle and Week 24 of the 2nd and 3rd treatment cycle - Absolute change from baseline in Quality of Life domain scores as determined by SF-36 questionnaire at Week 24 of the 1st treatment cycle and Week 24 of the 2nd and 3rd treatment cycle - Percent of subjects who achieve amenorrhea at Weeks 4, 8, 12, 16, 20, 24 of the 1st treatment cycle and Weeks 8, 16, and 24 of the 2nd and 3rd treatment cycle and Follow-up visit ;Timepoint(s) of evaluation of this end point: - Pre-post change for every 4 weeks in EAPP - Intake of analgesic rescue medication for every 4 weeks - Pre-post change of each pain type associated with endometriosis at each visit - Proportion of patients responding to treatment based on change in VAS EAPP and intake of rescue medication after 12 and 24 weeks of double-blind treatment - Pre-post change in the total symptom and sign severity score by B &B scale - CGI & PGIC scale at Week 24 of the 1st cycle and Week 24 of the 2nd and 3rd cycle - Change from b | — |
Countries
Bulgaria, Hungary, Moldova, Republic of, Poland, Romania, Russian Federation, Serbia, Spain
Contacts
Public ContactProject Manager
Litaphar Laboratorios
Outcome results
None listed