Investigation of efficacy, safety and tolerability of estradiol vaginal tablets in postmenopausal women with vaginal atrophy MedDRA version: 20.0 Level: LLT Classification code 10047782 Term: Vulvovaginal atrophy System Organ Class: 100000004872
Conditions
Interventions
Product Name: Estradiol 10 µg vaginal tablets
Pharmaceutical Form: Vaginal tablet
INN or Proposed INN: ESTRADIOL HEMIHYDRATE
CAS Number: 35380-71-3
Sponsors
Helm AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age: 18 years or older 2. Good state of health commensurate with age 3. Postmenopausal state defined as follows: - last spontaneous menstruation at least 1 year prior to the study and FSH (plasma) >= 40 IU/l, estradiol (serum) 5.0 6. Investigator’s assessment of vaginal health: visually assessed signs of vaginal atrophy (a thinned vaginal mucosa or a mucosa with flattening of folds; a dry, fragile, or pale vaginal mucosa; the presence of petechiae or any other alteration that the investigator considers indicative of vaginal atrophy) 7. At least one urogenital symptom self-assessed by the subjects (vaginal dryness, vaginal and/or vulvar irritation/itching, vaginal soreness, dysuria, dyspareunia, vaginal bleeding associated with sexual activity, recurrent vaginal infections, hyperactive bladder with urge incontinence or stress incontinence 8. Non-smoker or ex-smoker for at least 6 months 9. Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in this clinical trial 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 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: Safety concerns 1. Existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient 2. Existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient 3. History of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders 4. Known allergic reactions/hypersensitivity to the active ingredient used or to constituents of the pharmaceutical preparations 5. Subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator 6. Systolic blood pressure > 145 mmHg 7. Diastolic blood pressure >90 mmHg 8. Pulse rate 100 bpm 9. Any laboratory value outside of normal and judged by investigator as relevant for participation under safety considerations 10. Any further contraindication to estrogen therapy - Known, past or suspected breast cancer - Known, past or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer) - Genital bleeding - Untreated endometrial hyperplasia - Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism) - Known thrombophilic disorders - Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction) - Porphyria 11. If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment - Leiomyoma (uterine fibroids) or endometriosis - Risk factors for thromboembolic disorders - Risk factors for oestrogen-dependent tumours, e.g. 1st degree heredity for breast cancer - Untreated or uncontrolled hypertension - Liver disorders (e.g. liver adenoma) - Diabetes mellitus with or without vascular involvement - Cholelithiasis - Migraine or (severe) headache - Systemic lupus erythematosus - A history of endometrial hyperplasia - Epilepsy - Asthma - Otosclerosis 12. Diagnosis of a cervical smear: findings classified in a group higher than IIa according to the Munich III nomenclature (or corresponding findings according to the Bethesda system) 13. For females with an intact uterus: no confirmation of an inactive endometrial lingering and/or endometrial thickness of =5 mm 14. Vaginal infection requiring further treatment 15. Hormone replacement therapy, therapy with phytoestrogens, local vaginal hormonal therapy or other drugs acting on the estrogen receptor within 3 months prior to first IMP administration (e.g. diethylstilbestrol, tibolone, SERM) 16. Use of systemic or intravaginal corticosteroids within 8 weeks prior to first IMP administration Lack of suitability for the clinical trial 17. Acute or chronic diseases which may interfere with the pharm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Aims of this clinical trial are: - Characterisation and comparison of efficacy of Test vs. Reference with regard to pharmacodynamic (PD) surrogate parameters (primary endpoints: change from baseline of vaginal maturation value after 2 weeks of treatment and change from baseline of vaginal pH after 6 weeks of treatment) - Assessment of superiority of Test vs. Placebo with regard to PD primary endpoints - Assessment of therapeutic equivalence of Test vs. Reference with regard to PD primary endpoints - Characterisation of systemic exposure by means of AUC- and Cmax–values of Test and Reference vaginal tablets containing 10 µg estradiol on Day 14 after multiple dose vaginal application (PK group) - Descriptive characterisation of safety and tolerability of the Test and Reference treatments. ;Secondary Objective: Not applicable; Primary end point(s): Efficacy: - Change from baseline of vaginal maturation value (MV) after 2 weeks of treatment - Change from baseline of vaginal pH after 6 weeks of treatment ; Timepoint(s) of evaluation of this end point: Efficacy: - Change in vaginal maturation value (MV) after 2 weeks of treatment - Change in vaginal pH after 6 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: - Investigator’s assessment of vaginal health (signs of vaginal atrophy) - Self-assessment by the subjects (symptoms of vaginal atrophy) Safety - AEs, local tolerability, systemic exposure to estradiol ; Timepoint(s) of evaluation of this end point: Assessment of signs and symptoms of vaginal atrophy after 2 and 6 weeks of treatment Safety - AEs, local tolerability after 2 and 6 weeks of treatment - systemic exposure to estradiol after 2 weeks of treatment | — |
Countries
Bulgaria, Germany, Moldova, Republic of
Contacts
Public ContactClinical Trials
Helm AG
Outcome results
None listed