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 myoma Sys
Conditions
Interventions
Product Name: ulipristal acetate
Product Code: PGL4001
Pharmaceutical Form: Tablet
INN or Proposed INN: ulipristal
CAS Number: 126784-99-4
Current Sponsor code: PGL4001
Other descriptive name: VA2914
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 PGL09-027 study related procedures. 2. Subject completed visit 6 of PGL09-026 study, 10 to 18 days after menstruation following end of treatment with PGL4001, and did not take medications forbidden by the protocol. 3. Subject has no contraindication to enter the extension study, based on the responsible investigator’s judgment. 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 200 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. Subject has a large uterine polyp (> 2cm). 2. Subject has one or more ovarian cysts = 4cm diagnosed by ultrasound at visit 6 of PGL09-026. 3. 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), acetylsalicylic acid, mefenamic acid, anticoagulants such as cumarins, antifibrynolytic drugs such as tranexamic acid, treatments containing PgP substrates (digoxin, fexofenadine), and/or treatments containing moderate or potent inhibitors or inducers of CYP3A4. 4. Subject has abnormal hepatic function at re-test (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). A re-test will be performed if hepatic function test values are above twice the upper limit of normal at visit 5 of PGL09-026 study. If the second test result is still above twice the upper limit of normal, the subject cannot be included. In case of isolated GGT, the subject may be enrolled if the re-test is within the allowed limits. 5. Subject has a lactose or galactose intolerance (i.e. lapp lactase deficiency or glucose-galactose malabsorption) 6. Subject has a positive pregnancy test or is planning a pregnancy during the course of the study. 7. Subject has a current problem with alcohol or drug abuse. 8. 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. 9. Subject has clinically significant abnormal findings at visit A or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject’s safety or interfere with study evaluations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the sustained efficacy of three 3-month treatment cycles of ulipristal acetate on myoma symptoms, specifically uterine bleeding. ;Secondary Objective: Efficacy: • To assess the sustained efficacy of three 3-month treatment cycles of ulipristal acetate on myoma symptoms other than uterine bleeding (i.e. myoma size, pain, quality of life (QoL)). Safety: • To assess the overall safety of the on-off 3-month administration of PGL4001 for up to a total of four treatment cycles (including PGL09-026 PEARL III treatment cycle). Exploratory: • To assess, recruitment permitting, the long-term clinical efficacy and safety benefit of following each of the three 3-month treatment cycles with ulipristal acetate by a ten-day course of norethisterone acetate or placebo ;Primary end point(s): Primary efficacy endpoint: •Percentage of subjects in amenorrhea at the end of each course of PGL4001 treatment received. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: Efficacy: •Change from baseline (measured at baseline in PGL09-026 study) to approximately 14 days after start of menses following each of the three PGL4001 and norethisterone acetate or placebo treatment periods and at follow-up (respectively visit B, visit C, visit D and visit F), in myoma size, measured on the three largest myomas identified at visit 1 of PGL09-026, by transvaginal ultrasound. •Change from baseline to visit B, visit C, visit D and to visit F in patient-reported pain using the short-form McGill Pain Questionnaire. •Change from baseline to visit B, visit C, visit D and to visit F in quality of life measured using the specific UFS-QoL questionnaire. •Change from baseline to visit B, visit C, visit D and to visit F in quality of life measured using the general EQ-5D questionnaire. Safety: •Changes from baseline observed during a physical examination •Changes from baseline observed during a gynaecological and/or breast examination. •Changes from baseline observed in vital sign measurements, ECG. •Changes from baseline observed in endometrial thickness assessed by transvaginal ultrasound. •Changes from baseline of the ovary observed by transvaginal ultrasound. •Serum levels of estradiol (E2). •Changes from baseline in serum Adrenocorticotropic hormone (ACTH), Thyroid Stimulating Hormone (TSH) and prolactin levels. •Change from baseline in the following laboratory parameters: haematology, coagulation, biochemistry and lipids. •Changes from baseline in endometrium biopsy (i.e. hyperplasia, adenocarcinoma). •Number and proportion of subjects experiencing treatment-emergent adverse events including patient-reported adverse events and clinically significant changes in the parameters listed above. Exploratory: •Assessment of the strength of the first menstrual bleed after each PGL4001 treatment, using the Pictorial Bleeding Assessment Chart (PBAC). •Time to return of menstruation fo | — |
Countries
Austria, Belgium, Poland, Spain
Contacts
Public ContactRegulatory Affairs Associate
PregLem S.A.
Outcome results
None listed