ESTRIOL for Vaginal atrophy

Inclusion criteria

• {"criterion_text":"- 1. Age: 45 years or older"}
• {"criterion_text":"- 2. Postmenopausal state defined as last spontaneous menstruation at least 1 year prior to the study and FSH (serum) ≥ 40 IU/l (≥ 40 E/l)"}
• {"criterion_text":"- 3. Vaginal Maturation Value (MV) ≤ 50% at screening"}
• {"criterion_text":"- 4.\tVaginal pH > 5.0 at screening"}
• {"criterion_text":"- 5.\tAt least one subjective symptom of VA (dryness, pain/burning sensation, pruritus, discharge, dysuria, urinary incontinence, dyspareunia) rated at a score of ≥ 65 on the Visual Analogue Scale (VAS)"}
• {"criterion_text":"- 6.\tNon-smoker or ex-smoker for at least 3 months"}
• {"criterion_text":"- 7.\tWritten 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 participants in this clinical trial"}

Exclusion criteria

• {"criterion_text":"- 1.\tHistory or presence of cardiac and/or haematological diseases or pathological findings, which, in the opinion of the investigator, might interfere with the safety or tolerability of the active ingredient"}
• {"criterion_text":"- 2.\tHistory or presence of hepatic and/or renal diseases or pathological findings, which, in the opinion of the investigator, might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient"}
• {"criterion_text":"- 3.\tHistory or presence of relevant Central Nervous System (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders, which in the opinion of the investigator, might affect the safety of the participant"}
• {"criterion_text":"- 4.\tKnown allergic reactions/hypersensitivity to the active ingredient used or to constituents of the pharmaceutical preparations"}
• {"criterion_text":"- 5.\tParticipants with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator"}
• {"criterion_text":"- 6.\tSystolic blood pressure > 139 mmHg"}
• {"criterion_text":"- 7.\tDiastolic blood pressure >89 mmHg"}
• {"criterion_text":"- 8.\tPulse rate < 50 bpm or > 100 bpm"}
• {"criterion_text":"- 9.\tAny clinically relevant abnormality as observed during breast examination at screening"}
• {"criterion_text":"- 10.\tAny laboratory value outside of normal and judged by investigator as relevant for participation under safety considerations"}
• {"criterion_text":"- 11.\tAny further contraindication to estrogen therapy; Known, past or suspected breast cancer; Known, past or suspected oestrogen-dependent malignant tumours (e.g. endometrial cancer); Current or undiagnosed genital bleeding; Untreated endometrial hyperplasia; Previous or current venous thromboembolism (deep venous thrombosis, pulmonary embolism); Known thrombophilic disorders; Active or recent (within the last 24 months) arterial thromboembolic disease (e.g. angina pectoris, myocardial infarction) if not cured without cardiovascular consequences; Porphyria"}
• {"criterion_text":"- 12.\tIf any of the conditions listed below are present or have occurred previously. Patients might participate if either these conditions have not aggravated during pregnancy or previous sex hormone treatment, or if they are judged by the investigator not to pose a current safety risk for the participant; Leiomyoma (uterine fibroids) or endometriosis; Risk factors for thromboembolic disorders; Risk factors for oestrogen-dependent tumours, e.g. 1st degree relative for breast cancer; Untreated or uncontrolled hypertension; Liver adenoma or estrogen-dependent liver disorders (e.g. liver cysts, liver angioma); uncontrolled Diabetes mellitus; Cholelithiasis; Migraine or category II or higher non-migraine headaches (grading of non-migraine headaches acc. to Sjaastad et al. 2002); Systemic lupus erythematosus; A history of endometrial hyperplasia (endometrial thickness of ≥ 5 mm); Epilepsy; Asthma; Otosclerosis; Endometrial polyps"}
• {"criterion_text":"- 13.\tDiagnosis of a cervical smear: findings classified in a group higher than IIa according to the Munich III nomenclature or history of documented abnormal cervical smear (higher than IIa) within one year of screening"}
• {"criterion_text":"- 14.\tConfirmation of endometrial thickness of ≥ 5 mm"}
• {"criterion_text":"- 15.\tUntreated vaginal infection that would hinder the insertion of the ring according to the decision of the investigator"}
• {"criterion_text":"- 16.\tThe following washout periods must be observed before screening: 1 week or longer for prior non-hormonal vaginal or vulvar treatment (including cosmetics expected to affect vaginal pH such as special feminine wash gels); 4 weeks or longer for prior vaginal hormonal products (rings, creams, gels); 4 weeks or longer for prior transdermal estrogen alone or estrogen/progestin products; 8 weeks or longer for prior oral estrogen and/or progestin therapy; 8 weeks or longer for prior intrauterine progestin therapy; 8 weeks or longer for prior testosterone or testosterone derivatives, DHEA, tibolone, or SERMs by any route; 3 months or longer for prior progestin implants and estrogen alone injectable drug therapy; 6 months or longer for prior estrogen pellet therapy or progestin injectable drug therapy"}
• {"criterion_text":"- 17.\tUse of systemic or intravaginal corticosteroids within 8 weeks prior to the IMP administration"}
• {"criterion_text":"- 18.\tTreatment with strong inductors or inhibitors of CYP3A4, e.g. anticonvulsants (barbiturates, hydantoins, carbamazepine), certain antibiotics (e.g. erythromycin, clarithromycin, telithromycin), antimycotics (e.g. ketoconazole, itraconazole) and other antiinfective medicinal products (e.g. rifampicin, rifabutin, nevirapine, efavirenz); phenylbutazone; ritonavir and nelfinavir; preparations based on medicinal plants that contain St. John’s Wort within 2 weeks prior to the IMP administration"}
• {"criterion_text":"- 19.\tWomen with hysterectomy and/or bilateral oophorectomy"}
• {"criterion_text":"- 20.\tAcute or chronic diseases which may interfere with the aims of the clinical trial"}
• {"criterion_text":"- 21.\tVaginal descensus or other condition which might interfere with the vaginal application of IMP"}
• {"criterion_text":"- 22.\tHistory of or current drug or alcohol dependence or abuse"}
• {"criterion_text":"- 23.\tParticipation in a clinical trial with administration of any investigational medicinal product during the last 2 months prior to screening"}
• {"criterion_text":"- 24.\tSimultaneous participation in another clinical trial with active ingredients"}
• {"criterion_text":"- 25.\tParticipant is judged by the Investigator to be unsuitable for any reason"}
• {"criterion_text":"- 26.\tNon-availability of prompt access to eDiary at any time"}
• {"criterion_text":"- 27.\tParticipants suspected or known not to follow instructions"}
• {"criterion_text":"- 28.\tParticipants who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial"}
• {"criterion_text":"- 29.\tParticipant is vulnerable such as detained or committed to an institution by a court of law or by legal authorities or has close affiliation with the sponsor or the investigational site (e.g. a close relative, dependent person (e.g. employee or student))"}
• {"criterion_text":"- 30.\tPositive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if positive to be verified by test for HBc-IgM) or anti-HCV-test"}

Primary endpoints

• {"endpoint_text":"- Change from baseline in vaginal Maturation Value (MV) after 90 days of treatment","definition_or_measurement_approach":"Change from baseline measured after 90 days of each treatment (as stated in main objective: descriptive evaluation after 90 days of each treatment)."}
• {"endpoint_text":"- Change from baseline in % of vaginal superficial cells after 90 days of treatment","definition_or_measurement_approach":"Change from baseline measured after 90 days of each treatment."}
• {"endpoint_text":"- Change from baseline in % of vaginal parabasal cells after 90 days of treatment","definition_or_measurement_approach":"Change from baseline measured after 90 days of each treatment."}
• {"endpoint_text":"- Change from baseline in vaginal pH after 90 days of treatment","definition_or_measurement_approach":"Change from baseline measured after 90 days of each treatment."}
• {"endpoint_text":"- Proportion of responders with a vaginal pH ≤ 5 after 90 days of treatment","definition_or_measurement_approach":"Proportion of participants achieving vaginal pH ≤ 5 at 90 days of treatment."}
• {"endpoint_text":"- Total (AUC) E3 exposure over the course of treatment","definition_or_measurement_approach":"Total systemic estriol (E3) exposure measured as AUC over the course of treatment; main objective notes systemic total E3 exposure evaluated in a subgroup of patients (PK subgroup)."}

Methods

• Recruitment material_SocialMedia (document K2_Recruitment material_SocialMedia_2024-514302-31-00_redacted) - social media channel indicated
• Recruitment material_Advert (document K1_Recruitment material_Advert_2024-514302-31-00_redacted) - advertisement material indicated
• Recruitment material_PreScreen (document K2_Recruitment material_PreScreen_2024-514302-31-00_redacted) - pre-screening material indicated
• Recruitment material_E-Mail (document K3_Recruitment material_E-Mail_2024-514302-31-00_redacted) - e-mail channel indicated

Germany

Earliest CTIS Part Ii Submission Date

10-06-2025

Latest Decision Or Authorization Date

12-12-2025

Processing Time Days

185

Number Of Sites

7

Number Of Participants

112

Primary sponsor

Full Name

SocraTec R&D Concepts in Drug Research and Development GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"SGS Analytics Germany GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"HWI pharma services GmbH","duties_or_roles":"IMP packaging, labelling, QP certification (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"LKF Laboratorium fuer Klinische Forschung GmbH","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"SocraMetrics GmbH","duties_or_roles":"sponsorDuties codes: [10, 6, 8]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"ACC GmbH Analytical Clinical Concepts","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MVZ Duesseldorf-Centrum GbR","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Hospital/Clinic/Other health care facility"}