E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
symptomatic uterine myoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046801 |
E.1.2 | Term | Uterine myoma |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective of this study is to demonstrate non inferior efficacy of PGL4001 versus GnRH-agonist to reduce, prior to surgery, excessive uterine bleeding caused by uterine myomas. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to demonstrate improvement over baseline in myoma-related symptoms such as impaired Quality of Life (QoL) and pain, and to assess PGL4001 capacity to decrease uterine volume as well as volume of the three largest myomas |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be included, subject must: Provide written informed consent prior to any study related procedures. Be a pre-menopausal woman between 18 and 50 years inclusive. Have a PBAC score >100 during day 1 to day 8 of menstruation preceding the baseline visit. Have a myomatous uterus volume ≤ 16 weeks. Have at least one uterine myoma of ≥ 3 cm diameter in size and no myoma larger than 10 cm diameter in size diagnosed by ultrasound. Be eligible for one of these surgical procedures: i.e. hysterectomy, myomectomy, uterine artery embolization or endometrial ablation within 13 weeks and up to 14 weeks from baseline study visit. Have a clinical breast examination without significant findings at the screening visit. Have no clinically significant findings at Papanikolaou test (PAP) smear, performed within the past 12 months or at the screening visit. If of childbearing potential the subject must be practicing a non-hormonal method of contraception as listed below: -Sexual abstinence -Diaphragms -Condom or partner with a vasectomy performed at least 6 months prior to the study and confirmed azoospermia. If of non childbearing potential, the subject must have had a tubal ligation sterilisation at least two months before study start. Have a Body Mass Index (BMI) ≥ 18 and ≤ 40. |
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E.4 | Principal exclusion criteria |
Subject will be excluded from participation; if she: Has a history of uterus surgery (except caesarean section or cervical conisation), endometrial ablation or uterine artery embolization. Has a history of or current uterine, cervical, ovarian or breast cancer. Has a history of or current endometrium atypical hyperplasia or adenocarcinoma or similar lesions in the screening biopsy or in a biopsy performed within the past 6 months. Has a condition requiring immediate blood transfusion or a level of Hb ≤ 6 g/dL. Has a known hemoglobinopathy (i.e. Sickel Cell anaemia and Thalassämia). Has a known severe coagulation disorder. Has a large uterine polyp (> 2cm). Has one or more ovarian cysts ≥ 4cm in diameter diagnosed by Ultrasound (US). Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRH-agonist. Has been taking: - Treatments with progestins (systemic or progestin releasing intra-uterine system) or an oral contraceptive: within the month before the screening visit, - Acetylsalicylic acid and/or mefenamic acid: within one week before the screening visit, - Systemic glucocorticoid treatments and/or systemic depot glucocorticoid treatments within one week or two months before the screening visit, respectively. 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), oral contraceptives, systemic glucocorticoids (oral and injectable), acetylsalicylic acid and/or mefenamic acid. Has a history of or known current osteoporosis. Has abnormal hepatic function at study entry (defined as Aspartate transaminase (AST), Alanine transaminase (ALT), Gamma Glutamine Transferase (γGT), alkaline phosphatase or total bilirubin above 2 Upper Limit of Normal range (ULN)). Has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study. Has a current (within twelve months) problem with alcohol or drug abuse. Has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude. Has abnormal baseline findings, any other medical condition(s) or psychiatric condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subjects safety or interfere with study evaluations. Has an allergy to GnRH agonist, SPRMs or progestins or any of the ingredients of the study drug tablet (see list of ingredients in the investigators brochure), Is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary safety endpoint are the: - Mean serum E2 levels at end of treatment visit (Week 13 visit) for PGL4001 compared with GnRH-agonist. - Percentage of subjects reporting moderate or severe hot flushes as adverse events throughout the treatment period for PGL4001 compared with GnRH-agonist. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |