A Phase IIa, Double-Blind, Placebo-Controlled, Study of ESN364 Administered for 12 Weeks to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Women Presenting With Uterine Fibroids

Phase 1

• Conditions: terine Fibroids; MedDRA version: 17.1Level: LLTClassification code 10046784Term: Uterine fibroidsSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2014-004425-41-AT
• Lead Sponsor: Euroscreen S.A

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12-23
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 72

Inclusion Criteria

1) Has been diagnosed with uterine fibroids and never received surgical treatment for a myoma;
2) Is a pre-menopausal woman between 18 and 50 years inclusive at screening;
3) Has a clinical breast examination without clinically relevant findings at the screening visit;
4) Has a myomatous uterus with a size equivalent to a uterus of =16 weeks gestation and at least one measurable noncalcified fibroid =3 cm diameter but none ?10 cm diameter as measured by TVU (the three largest myoma's are to be followed up);
5) Willing to undergo an endometrial biopsy at Visit 2 and at Week 12 (end-of-treatment);
Has been diagnosed with menorrhagia (PBAC >100 during the first 8 days of the menses); otherwise having a regular menstrual cycle (21-36 days);
7) Body Mass Index (BMI) between 18 – 33 kg/m² inclusive;
8) Has a negative (normal or atypical squamous cell of uncertain significance) cervical smear (Papanikolaou test [PAP], cytobrush or equivalent) within 36 months prior to screening;
9) In good physical and mental health as determined on the basis of medical history and general physical examination performed at screening;
10) Hematology and chemistry parameters, heart rate (HR) and/or blood pressure, and electrocardiogram ECG within the reference range for the population studies, or showing no clinically relevant deviations, as judged by the investigator;
11) Negative urine test for selected drugs (amphetamines benzodiazepines, cannabinoids, cocaine, tetrahydrocannabinol, barbiturates or opiates) of abuse at screening and before first administration of study drug;
12) Has a negative pregnancy test at screening;
Note: pregnancy testing will consist of a serum pregnancy test at screening and urine pregnancy tests at other visits.
13) Females who are not breast-feeding;
14) Women of childbearing potential agrees not to get pregnant and willing to be abstinent or to use adequate highly effective contraception (failure rate less than 1% per year) during the trial and for at least 42 days after end of treatment;
The following non-hormonal contraceptive methods are defined as acceptable:
o Partner with a vasectomy performed at least 3 months prior to the study and with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. (The vasectomized male partner should be the sole partner for that subject).
o True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptom-thermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
o The subject is homosexual/has no intercourse with the opposite sex
o Partner is using condoms in combination with spermicidal cream or gel Women of childbearing potential are defined as any female who has experienced menarche and are not post-menopausal or permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy);
15) Informed Consent Form (ICF) signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study.
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 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1)Has a hemoglobin value <9 g/dL at screening;
2)Has a follicle stimulating hormone (FSH) value >30 mIU/mL at screening;
3)Has a history of or currently ongoing hemoglobinopathy (i.e. Sickle Cell anemia and Thalassemia) or coagulopathies;
4)Has a known history of severe hypersensitivity or severe allergy to sanitary goods;
5)Has a history of uterine surgery (except Caesarean section or cervical conization) or bilateral oophorectomy;
6)Has a history of a previous endometrial ablation or uterine artery embolization;
7)Judged by investigator to have marked abnormal uterine bleeding; or non-diagnosable abnormal genital bleeding; or anovulatory bleeding;
8)Has regular abdominal discomfort or pain due to gastro-intestinal, urological or gynecological conditions other than UF;
9)Has a history of or currently ongoing pelvic inflammatory disease;
10)Has a history of or currently ongoing malignant tumor (except for basal cell carcinoma of the skin that has been treated with no evidence or recurrence);
11)Has been treated within 3 months of screening with any of the following drugs: gonadotrophin releasing hormone (GnRH) agonist/antagonist, selective estrogen receptor modulator (SERM), selective progesterone receptor modulator (SPRM), dienogest, danazol aromatase inhibitor, anticoagulant drugs, antiplatelet drug, glucocorticoids, mineralocorticoids, androgens, depot contraceptive preparations or vitamin K;
12)Treatment with hormonal contraceptives (oral, transdermal, coated intrauterine device) and/or tranexamic acid should be stopped 1 month prior to screening;
13)Has a known severe allergy, hypersensitivity, or intolerance to any drug, including the study drug and any of its excipients;
14)Judged by investigator to be inappropriate to participate in this study based on findings observed during the general physical/gynecological examination (including endometrial hyperplasia on the biopsy of Visit 2); or clinically relevant findings on the 12-lead ECG;
15)Has a contraindication for undergoing an MRI scan (e.g., unsuitable body weight, claustrophobia, pacemaker, …);
16)Has active liver disease or jaundice, or with out-of-range values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); or total bilirubin >1.3 times the upper limit of normal (ULN); or creatinine >1.25 times the ULN at screening;
17)Has a medical condition or chronic disease (including neurological [including cognitive], hepatic, renal, cardiovascular, gastrointestinal, pulmonary, or endocrine disease), or malignancy that could confound interpretation of the study outcome as judged by the investigator;
18)Has any psychological disorder according to criteria indicated in the Diagnostics and Statistical Manual of Mental Disorders, 4th edition within one year before screening. Such disorders include, but are not limited to, alcohol (more than 3 glasses of wine, beer, or equivalent/day) and substance abuse/dependence within 2 years prior to the initial study medication administration;
19)Has a history of poor compliance in clinical research studies;
20)Has a positive hepatitis panel (including hepatitis B surface antigen [HBsAg] or anti-hepatitis C virus [HCV] antibodies) or positive human immunodeficiency virus (HIV) antibody at screening;
21)Presence or sequelae of gastrointestinal, liver, kidney or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs, as judged by the i

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified