Uterine myomas are benign, monoclonal, hormone-sensitive, smooth muscle tumours of the uterus. They are the most common tumour of the female reproductive tract in pre-menopausal women and mostly asymptomatic affecting approximately 40% of women between 35 and 55 years. When symptomatic, the main symptoms are heavy uterine bleeding, abdominal pressure, abdominal pain, increased urinary frequency and infertility. MedDRA version: 14.1 Level: LLT Classification code 10046801 Term: Uterine myo
Conditions
Interventions
Product Name: ulipristal acetate
Product Code: PGL4001
Pharmaceutical Form: Tablet
INN or Proposed INN: ulipristal (INN) acetate
CAS Number: 126784-99-4
Current Sponsor code: PGL4001
Concentration un
Sponsors
PregLem S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for inclusion into this study, the subjects must fulfil all of the following criteria: 1. Provision of written informed consent prior to any study related procedures. 2. Pre-menopausal women between 18 and 50 years inclusive. 3. Subject with a Body Mass Index =18 and =40. 4. Subject with hormonal levels FSH = 20 mIU/mL (measured at screening 2 visit). 5. Subject with myomatous uterus 100 as measured during screening over the first 8 days of the menstrual bleed 9. Subject has no significant findings at breast examination at the screening visit. 10. Females of childbearing potential are advised to practice a non-hormonal method of contraception among one of the following: o Sexual abstinence o Diaphragm o Condom o Or having a partner with a vasectomy with either confirmed azoospermia or performed at least 6 months prior to the study. Females of non-childbearing potential are defined as women with tubal ligation sterilisation at least two months before the start. 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: To be eligible for inclusion in this study the subjects must not meet any of the following criteria: 1. The subject has a history of uterus surgery that would interfere with the study endpoints. The investigator must assess whether a previous surgery is likely to interfere with the study. Subjects who had a uterine artery embolization may be included in the study = 6 months after the procedure. 2. The subject has a history of or current uterus cervix, ovarian or breast cancer. 3. The subject has had a significant and persisting finding on Papanikolaou test (PAP) smear within the past 12 months. 4. The subject has a history of endometrium hyperplasia or adenocarcinoma or similar lesions in the screening biopsy. If by exception the endometrium biopsy results are only made available after subject’s visit 2, the Investigator will follow the instructions listed in Appendix G. 5. Subject has a large uterine polyp (> 2cm). 6. Subject has extensively calcified myomas and/or uterus. 7. Subject has a known severe coagulation disorder. 8. Subject has one or more ovarian cysts = 4cm diagnosed by ultrasound. 9. The subject has a history of treatment for myoma with a SPRM. 10. The subject has been taking prohibited medication : o Treatments with progestins (systemic or progestin releasing intra-uterine system) or an oral contraceptive: within the month before the screening visit. o Acetylsalicylic acid, mefenamic acid, anticoagulants such as cumarins and/or antifibrinolytic drugs such as tranexemic acid within one week before the screening visit o Systemic glucocorticoid treatments and/or systemic depot glucocorticoid treatments within one week or two months before the screening visit, respectively. o GnRH agonist and antagonist: ? Immediate or monthly sustained release depot preparation or immediate release form within 6 months of screening visit ? 3 or 6 months sustained release depot preparation within 12 months before the screening visit. 11. The subject is likely to require treatment during the study with drugs that are not permitted by the study protocol: progestins (systemic or progestin releasing intra-uterine system), hormonal contraceptives, systemic glucocorticoids (oral and injectable), GnRH agonist and GnRH antagonists. 12. The subject requires treatment with a medication which includes potent inhibitors of CYP3A4 (such as ketoconazole) 13. The subject requires treatment with a medication which includes potent inducers of CYP3A4 (such as rifampicin). 14. The subject has abnormal hepatic function at study entry (defined as aspartate transaminase [AST], alanine transaminase [ALT], gamma glutamyl transferase [GGT], hepatic alkaline phosphatase, or total bilirubin above twice the upper limit of normal). In case of isolated elevated GGT, the subject may be enrolled if the re-test is within the allowed limits. 15. The subject has a positive pregnancy test at baseline, is nursing or planning a pregnancy during the course of the study. 16. The subject has a problem with alcohol or drug abuse. 17. The subject has a mental condition rendering her unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude. 18. The subject has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject’s safety or interfere with study evaluations. 19. The subject has an aller
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part I Primary Objective: To compare and assess the sustained efficacy of two repeated 12-week treatment courses of daily administration of 5mg and 10mg doses of PGL4001 on uterine bleeding in women with uterine fibroids. Part II Primary Objective: To compare and assess the sustained efficacy of four repeated 12-week treatment courses of daily administration of 5mg and 10mg doses of PGL4001 on uterine bleeding in women with uterine fibroids. ;Secondary Objective: Part I Secondary Objectives: Efficacy objective: • To compare and assess the sustained efficacy of two repeated 12-week treatment courses of daily administration of 5mg and 10mg doses of PGL4001 on myoma volume, uterus volume, Quality of Life (QoL), and pain. Safety objective: • To assess the overall safety of two repeated 12-week treatment courses of daily administration of 5mg or 10mg of PGL4001. Part II Secondary Objectives: Efficacy objective: • To compare and assess the sustained efficacy of four repeated 12-week treatment courses of 5mg and 10mg doses of PGL4001 on myoma volume, uterus volume, Quality of Life (QoL), and pain. Safety objective: • To assess the overall safety of four repeated 12-week treatment courses of daily administration of 5mg or 10mg doses of PGL4001. ;Primary end point(s): PART I Primary Efficacy Endpoint: Percentage of subjects who are in amenorrhea at the end of both treatment courses 1 and 2. Amenorrhea is defined as no more than 1 day of spotting within a 35 day interval. PART II Primary Efficacy Endpoint: Percentage of subjects who are in amenorrhea at the end of all four treatment courses. ;Timepoint(s) of evaluation of this end point: As soon as the last subject has completed Part I of the protocol and all data have been cleaned, the treatment groups will be unblinded, and the results up to and including the visit following the second course of treatment (visit 8) will be analysed (Full integrated Clinical Study Report [CSR]). As soon as the las | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints Part 1: Efficacy: • Percentage of subjects who are in amenorrhea at the end of treatment course 1 and at the end of treatment course 2. • Percentage of subjects in amenorrhea in the last 56 days of both treatment courses 1 and 2. • Percentage of subjects in amenorrhea in the last 56 days of treatment course 1 and in the last 56 days of treatment course 2. • Percentage of subjects with controlled bleeding in the last 56 days of both treatment courses 1 and 2. Controlled bleeding is defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a course of treatment. • Percentage of subjects with controlled bleeding in the last 56 days of treatment course 1 and in the last 56 days of treatment course 2. • Proportion of days with uterine bleeding between visit 2 and visit 8. • Proportion of days with heavy uterine bleeding between visit 2 and visit 8. • Median time to amenorrhea during treatment course 1 and during treatment course 2. • Change from baseline to visits 6, 7 and 8 in the volume of the 3 largest myomas, measured by transvaginal ultrasound. • Change from baseline to visits 6, 7 and 8 in uterus volume, measured by transvaginal ultrasound. • Change from baseline to end of treatment course 1 and to end of treatment course 2 in quality of life, measured with the UFS- QoL questionnaire. • Change from baseline to end of treatment course 1 and to end of treatment course 2 in quality of life, measured with the EQ-5D questionnaire. • Change from baseline to end of treatment course 1 and to end of treatment course 2 in pain, measured using a Visual Analog Scale (VAS). Safety: • Number and proportion of subjects withdrawing from treatment early for safety reasons related to study drug. • Number and proportion of subjects experiencing treatment-emergent adverse events including subject-reported adverse events and clinically significant changes in the following p | — |
Countries
Belgium, Czech Republic, Germany, Hungary, Italy, Latvia, Lithuania, Poland, Russian Federation, Ukraine, United Kingdom
Contacts
Public ContactGeneral Information Desk
PregLem S.A.
Outcome results
None listed