SteinLeventhal syndrome
Conditions
Interventions
Two doses of ESN364 (60mg and 180mg) and a placebo group will be studied. Each
participant will receive one oral dose of ESN364 (60 mg/180 mg) or identical
placebo during 12 weeks.
Subjects will be
Polycystic Ovarian Syndrome
Sponsors
Ogeda S.A
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1) Pre-menopausal woman between 18 and 45 years inclusive at screening;;2) Diagnosed with PCOS according to the Rotterdam criteria with the following modification: biochemical hyperandrogenism is mandatory (TT > 50 ng/dL [1.7 nmol/L] at screening and at least one of the following two other Rotterdam criteria are additionally required for diagnosis of PCOS:;* Oligomenorrhea (*6 menses per year) or oligo-ovulation and/or ;* Polycystic ovaries on ultrasound (*12 antral follicles in at least one ovary or ovarian volume *10 cm3);;3) Normal thyroid function (thyroid stimulating hormone [TSH] compatible with normal thyroid function); mild hypothyroidy treated with stable hormone replacement therapy is allowed if TSH is normal;;4) FSH and E2 within normal limits as judged by the investigator;5) Normal prolactin (PRL) levels as judged by the investigator;;6) 17-hydroxy-progesterone levels compatible with normal 21-hydroxylase activity (<200 ng/dL (<6.1 nmol/L),In case of a sample taken in luteal phase levels < 286 ng/dL [<8.7 nmol/L] are acceptable.) ;;7) In good physical and mental health as determined on the basis of medical history and general physical examination performed at screening; 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;;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 or at screening and available before randomization;;9) 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;;10) Negative pregnancy test at screening and before randomization; not have been pregnant within 6 months prior to screening;;Note: pregnancy testing will consist of a serum pregnancy test at screening and urine pregnancy tests at other visits. ;11) 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: ;* 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).;* 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);* Hormone-free intrauterine device (copper intrauterine device) in combination with a condom;* The subject is homosexual/has no intercourse with the opposite sex;* 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);;12) Willing to adhere to the prohibitions and restrictions specified in the protocol;;13) Informed Consent Form (ICF)
Exclusion criteria
Exclusion criteria: 1) Evidence of diabetes diagnosed on any of the following World Health Organization (WHO) criteria:;- Fasting plasma glucose (FPG) *7.0 mmol/l (126 mg/dl) or,;- Glycated hemoglobin (HbA1c) *6.5% /48 mmol/mol or,;- Random plasma glucose *11.1 mmol/l (200 mg/dl) in the presence of classical diabetes symptoms;;2) Concomitant use of insulin sensitizers is not allowed, if taken, they should be stopped at screening;;3) Use of anti-androgens within 3 months prior to screening;;4) Have been treated within 3 months of screening with any of the following drugs: GnRH agonist/antagonist, selective estrogen receptor modulator (SERM), selective progesterone receptor modulator (SPRM), dienogest, danazol aromatase inhibitors, glucocorticoids, mineralocorticoids, androgens, and depot contraceptive preparations;;5) Treatment with hormonal contraceptives (oral, transdermal, coated intrauterine device) should be stopped 1 month prior to screening;;6) Has undergone bariatric surgery within 6 months prior to screening;;7) Has undergone ovarian surgery (drilling, wedge resection,*) within 6 months prior to screening;;8) Has undergone hysterectomy or bilateral oophorectomy or both;;9) Has Cushing*s syndrome;;10) Has a history of or currently ongoing pelvic inflammatory disease;;11) Has a known severe allergy, hypersensitivity, or intolerance to drugs in general, including the study drug and any of its excipients;;12) Has a history of or a currently ongoing malignant tumor (except for basal cell carcinoma of the skin that has been treated with no evidence of recurrence);;13) Has active liver disease or jaundice, or values for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.3 times the upper limit of normal (ULN); or total bilirubin >1.3 times the ULN; or creatinine >1.25 times the ULN at screening;;14) 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;;15) Hemoglobin level 500 mL]) or had a transfusion of any blood product within 12 weeks prior to the initial study medication administration;;19) 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 (e.g., condition requiring chronic treatment with valproic acid);;20) Has a history of poor compliance in clinical research studies;;21) Concurrent participation or participation within 3 months prior to screening in a drug/device or biologic investigational research study;;22) Subject is the investigator oor any sub-investigator, research assistant, pharmacist, study coordinator, or other staff or relative thereof who is directly involved in the cond
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in TT levels from baseline to end-of-treatment visit (Week 12). | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in menstrual cycle as measured by frequency menses, spotting, inter-menstrual bleedings Change in endometrium thickness, ovarian volume, number of follicles (cysts), and dominant follicle development (Y/N) assessed by 2D transvaginal ultrasound from baseline to Week 6 and Week 12 (end-of-treatment visit) Change from baseline in the PCOS Q score (total and subcategories) at Week 6 and Week 12 (end-of-treatment visit) Change in sex hormone levels (LH, free and TT levels) from baseline to Week 6, Week 12 (end-of-treatment), and Week 18 (Follow-up) Change in sex hormone levels (P4 and E2 levels) from baseline to Week 6, Week 12 (end-of-treatment), and Week 18 (Follow-up) Change in sex hormone levels (FSH and LH/FSH ratio) from baseline to Week 6, Week 12 (end-of-treatment), and Week 18 (Follow-up) Change in total testosterone (TT) levels from baseline to Week 9 (at trough PK levels). | — |
Countries
Austria, Belgium, Georgia, Germany, Netherlands
Outcome results
None listed