Perimenopausal DisorderPhase 4VioletNCT05156814
Comparative Study to Evaluate the Efficacy and Safety of the Fixed-dose Combination of Estradiol / Dydrogesterone in Perimenopausal Women
A Phase 4 study testing Femoston® 1, Femoston® 2, Duphaston and Klimadynon in people with Perimenopausal Disorder and Hot Flashes, run by Scientific Research Institute of Public Health, Russian Federation at 1 site in Russia.
Trial summary
To obtain new data allowing personalizing continuous hormonal therapy in perimenopausal women in Russia, the following clinical study is going to be conducted in the Russian Federation: Read more about this study
- Who is it for?
- Ages 40 to 55 years, women only
- Conditions the study is for
- Perimenopausal Disorder, Hot Flashes
- What is being tested?
- Femoston® 1, Femoston® 2, Duphaston and Klimadynon
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteRussia
- Study dates
- 29 Nov 2021to May 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Caucasian women in perimenopause (STRAW -1/ +1a) with an intact uterus.
- Age from 40 to 55 years old as of the time of screening.
- Absence of natural menstruations within 4 months, but not longer than for 12 months.
- 50 or more episodes of "hot flashes" in the last 7 days according to the patient diary (at the screening).
- Patients scoring more than 12 points on the Greene Scale.
- Follicle-Stimulating Hormone (FSH) levels more than 25 IU/L, estradiol levels less than 190 pmol/L.
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- Consent to the use of barrier methods of contraception.
- Body mass index <30 kg / m2.
- Signed Informed Consent Form.
- Mammography performed within 6 months prior to inclusion in the study.
- Absence of clinically significant deviations according to the results of medical examination: physical examination (including assessment of the state of the mammary glands), measurement of indicators of vital body functions (blood pressure, heart rate, respiratory rate and body temperature) and gynecological examination.
- The patient's consent to perform all research procedures and adhere to all restrictions provided for by the research protocol.
Who cannot join
- Smoking.
- Administration of drugs from the prohibited therapy list.
- Known hypersensitivity to estradiol, dydrogesterone, to the active component of the drug Klimadynon® (dry extract of rhizomes of cimicifuga racemose) or to any of the excipients of the study drugs.
- Pregnancy and breastfeeding.
- Abnormal uterine bleeding from the vagina of unclear etiology within 12 months before the screening stage.
- Breast cancer (diagnosed, suspected, or past).
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- Estrogen-dependent malignancies of the sex organs, including endometrial cancer (diagnosed, suspected, or past).
- Known or suspected progestogen-dependent neoplasms (e.g. meningioma).
- Untreated endometrial hyperplasia.
- Venous and arterial thrombosis/thromboembolism, currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic or hemorrhagic stroke; angina pectoris, transient ischemic attack).
- Diagnosed hereditary or acquired predisposition to arterial or venous thrombosis/thromboembolism (eg, hyperhomocysteinemia, deficiency of protein C, protein S or antithrombin III, the presence of antiphospholipid antibodies).
- Acute or chronic liver disease in history (in case of deviation from a norm of liver function indicators); benign and malignant liver tumors (including hemangioma, adenoma, liver cancer) or an increase in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) activity detected during screening by more than 1.5 times relative to the upper limit of normal.
- Porphyria.
- Epilepsy.
- Brain disorders and traumas.
- Galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
- Cholestatic jaundice and/or severe cholestatic itching (especially during a previous pregnancy or sex hormone intake).
- Uncontrolled hypertension.
- Diabetes mellitus.
- Adenomyosis grade >3 and uterine myoma (more than 3 nodes with an intermuscular or subserous arrangement with a diameter of more than 3 cm) and / or centripetal growth/submucous node location.
- Cholelithiasis.
- Systemic lupus erythematosus.
- Bronchial asthma.
- Otosclerosis.
- Known renal or hepatic insufficiency.
- Ovarian cysts >6 mm based on results of ultrasound scanning.
- Endometrial thickness ≥5 mm according to transvaginal ultrasound.
- Migraine headache or a history of severe migraine-type headaches.
- Other medical conditions which could interfere with the study-related procedures and/or influence the efficacy of the study drug.
- Simultaneous intake of excluded drugs.
- Participation in any other clinical study within 3 months before screening.
- Pathological result of smear for cytology (PAP test) and Human papillomavirus (HPV) test.
- The use of estrogens or combination drugs for hormone replacement therapy (HRT) within 6 months before the start of the study.
- Higher risk of thromboembolic complications due to prolonged immobilization for 2 weeks before the screening stage (for example, as a result of trauma or surgery).
- Previous major surgical interventions (including abdominal) within 6 months before the start of the study.
- Tumor of the pituitary gland.
- Severe pathology of the cardiovascular system: complicated lesions of the valvular apparatus of the heart, uncontrolled drug arrhythmia, chronic heart failure I - IV functional class.
- Sickle cell anemia.
- Congenital hyperbilirubinemia (Gilbert, Steven-Johnson and Rotor).
- A history of pancreatitis with severe hypertriglyceridemia.
- Polyp in the uterine cavity.
- Use of any drugs in the form of prolonged-release injections or implants within 3 months before the screening stage.
- A history of any other malignant neoplasms within 5 years prior to the study, with the exception of adequately treated squamous cell skin cancer.
- Anamnestic data on any clinically significant disease of the kidneys, lungs, gastrointestinal tract, skin and subcutaneous tissues, musculoskeletal system, blood and lymphatic system, nervous system.
- Positive blood test for HIV, hepatitis B and C, syphilis.
- Alcoholism, drug addiction in history.
- Prior endometrial ablation therapy.
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Federal State Budget Institution "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov"
Moscow
About this study
Official title: A Prospective, Multicenter, Randomized, Open-label, Comparative Study in Three Parallel Groups to Evaluate the Efficacy and Safety of the Fixed-dose Combination of Estradiol / Dydrogesterone (Femoston® 1 or Femoston® 2, Coated Tablets) and the Combination Therapy of Dydrogesterone (Duphaston®, Coated Tablets) Plus Estradiol (Divigel, Gel for Topical Application, 0.1%) and Monotherapy With Cimicifuga Racemosa Rhizomatum Extract (Klimadynon®) in Perimenopausal Women
To obtain new data allowing personalizing continuous hormonal therapy in perimenopausal women in Russia, the following clinical study is going to be conducted in the Russian Federation:
- Conditions
- Perimenopausal Disorder, Hot Flashes
- Being tested
- Femoston® 1, Femoston® 2, Duphaston, Klimadynon, Divigel
- Keywords
- hot flashes, Estradiol, Dydrogesterone, Cimicifuga racemosa, Perimenopausal Women
- Medical subject headings
- Hot Flashes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Femoston® 1, Femoston® 2Drug
Femoston® 1 (1 mg estradiol / 10 mg dydrogesterone), Femoston® 2 (2 mg estradiol / 10 mg dydrogesterone)
DuphastonDrug
Duphaston®, 10 mg
KlimadynonDrug
Cimicifuga racemosa rhizomatum extract
DivigelDrug
Divigel, 0.1%
| Study group | Role | What they receive |
|---|---|---|
| Fixed-dose Combination (FDC) estradiol / dydrogesterone | Experimental | Femoston® 1 (1 mg estradiol / 10 mg dydrogesterone), Femoston® 2 (2 mg estradiol / 10 mg dydrogesterone) Receives: Drug: Femoston® 1, Femoston® 2 |
| Combination therapy with estradiol and dydrogesterone | Active comparator | Duphaston®, 10 mg and Divigel, 0.1% Receives: Drug: Duphaston; Drug: Divigel |
| non-hormonal therapy | Active comparator | Cimicifuga racemosa rhizomatum extract (Klimadynon®) Receives: Drug: Klimadynon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the average number of "hot flashes" per day* as percentages according to data from the patient diary after 84 days (3 cycles) since the initiation of treatment compared to baseline (Visit 0).
Measured: 84 days
Secondary outcomes (11)
The change in the total score on the Greene Climacteric Scale at the end of the therapy (364 days) compared to baseline.
This scale includes 21 symptom-questions to assess the emotional-mental state (questions 1-11), somatic manifestations (questions 12 to 18), vasomotor status (questions 19 and 20) and sexual status (21 questions). There are 4 answer options for each question, as in the assessment of the Kupperman index: symptoms do not bother at all - 0 points, slightly bother - 1 point, bother quite strongly - 2 points, extremely pronounced - 3 points. Indicators characteristic of the presence of anxiety or depression - 10 points or more, scored in the first 11 questions. The presence of somatic disorders - 6 or more points in 12-18 questions. Violation of vasomotor function - 4 or more points in 19 and 20 questions.
Measured: 364 days
The frequency of "hot flashes" after 84 days since the initiation of treatment.
Measured: 84 days
Changes in the intensity of of menopausal symptoms calculated using the Menopause Rating Scale (MRS) after 84, 168, and 364 days since the treatment initiation compared to baseline (Visit 0).
The questionnaire has 11 items and option to check one of 5 degrees of severity of symptoms (from 0 (none) to 5 (very severe) points at the questionnaire).
Measured: 84 days, 168 days, 364 days
Changes according to the Greene Climacteric Scale in each of the 4 subscales after 84, 168, and 364 days since the initiation of treatment compared to baseline (Visit 0).
This scale includes 21 symptom-questions to assess the emotional-mental state (questions 1-11), somatic manifestations (questions 12 to 18), vasomotor status (questions 19 and 20) and sexual status (21 questions). There are 4 answer options for each question, as in the assessment of the Kupperman index: symptoms do not bother at all - 0 points, slightly bother - 1 point, bother quite strongly - 2 points, extremely pronounced - 3 points. Indicators characteristic of the presence of anxiety or depression - 10 points or more, scored in the first 11 questions. The presence of somatic disorders - 6 or more points in 12-18 questions. Violation of vasomotor function - 4 or more points in 19 and 20 questions.
Measured: 84 days, 168 days, 364 days
Changes according to the "Hot Flush" Related Daily Interference Scale (HFRDIS) after 84, 168, and 364 days since the initiation of treatment compared to baseline (Visit 0).
The HFRDIS is 10-item scale measuring the degree hot flashes interfere with nine daily activities.
Measured: 84 days, 168 days, 364 days
The average treatment satisfaction score according to the Likert Scale after 84, 168, and 364 days since the initiation of treatment.
Assessment of satisfaction with treatment is based on the patient's assessment of the degree of his consent or disagreement with the statements in a hierarchical sequence from "completely disagree" through "disagree", "find it difficult to answer", "agree" to "completely agree".
Measured: 84 days, 168 days, 364 days
Changes in the adipose tissue according to densitometry results after 364 days of treatment compared to baseline (Visit 0).
Measured: 364 days
Changes in the waist circumference after 364 days of treatment compared to baseline (Visit 0).
Measured: 364 days
Changes in the bone tissue according to densitometry results after 364 days of treatment compared to baseline (Visit 0).
Measured: 364 days
Changes in the bone resorption marker β-Cross laps after 364 days of treatment compared to baseline (Visit 0).
Measured: 364 days
Changes in the bone formation marker (P1NP) after 364 days of treatment compared to baseline (Visit 0).
Measured: 364 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2021
- Study start29 Nov 2021
- Primary completionSep 2022 (estimated)
- Study completionMay 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Perimenopausal DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Scientific Research Institute of Public Health, Russian Federation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05156814
- Sponsor's protocol ID
- ESDYC001
- Acronym
- Violet
- Status last verified
- Dec 2021
- First submitted
- 1 Dec 2021
- Last updated
- 6 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Randomized, Open-label, Comparative Study in Three Parallel Groups to Evaluate the Efficacy and Safety of the Fixed-dose Combination of Estradiol / Dydrogesterone (Femoston® 1 or Femoston® 2, Coated Tablets) and the Combination Therapy of Dydrogesterone (Duphaston®, Coated Tablets) Plus Estradiol (Divigel, Gel for Topical Application, 0.1%) and Monotherapy With Cimicifuga Racemosa Rhizomatum Extract (Klimadynon®) in Perimenopausal Women
- ClinicalTrials.gov ID
- NCT05156814
- Acronym / sponsor ID
- Violet / ESDYC001
- Conditions
- Perimenopausal Disorder, Hot Flashes
- Keywords
- hot flashes, Estradiol, Dydrogesterone, Cimicifuga racemosa, Perimenopausal Women
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Scientific Research Institute of Public Health, Russian FederationUniversity, hospital or other
- Study start
- 29 Nov 2021 (actual)
- Primary completion
- Sep 2022 (estimated)
- Study completion
- May 2023 (estimated)
- First posted
- 14 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To obtain new data allowing personalizing continuous hormonal therapy in perimenopausal women in Russia, the following clinical study is going to be conducted in the Russian Federation:
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fixed-dose Combination (FDC) estradiol / dydrogesterone | Experimental | Drug: Femoston® 1, Femoston® 2Femoston® 1 (1 mg estradiol / 10 mg dydrogesterone), Femoston® 2 (2 mg estradiol / 10 mg dydrogesterone) |
| Combination therapy with estradiol and dydrogesterone | Active comparator | Drug: Duphaston, Drug: DivigelDuphaston®, 10 mg and Divigel, 0.1% |
| non-hormonal therapy | Active comparator | Drug: KlimadynonCimicifuga racemosa rhizomatum extract (Klimadynon®) |
Who may qualify
- Ages
- 40 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Caucasian women in perimenopause (STRAW -1/ +1a) with an intact uterus.
- Age from 40 to 55 years old as of the time of screening.
- Absence of natural menstruations within 4 months, but not longer than for 12 months.
- 50 or more episodes of "hot flashes" in the last 7 days according to the patient diary (at the screening).
- Patients scoring more than 12 points on the Greene Scale.
Key exclusion criteria (47 listed)
- Smoking.
- Administration of drugs from the prohibited therapy list.
- Known hypersensitivity to estradiol, dydrogesterone, to the active component of the drug Klimadynon® (dry extract of rhizomes of cimicifuga racemose) or to any of the excipients of the study drugs.
- Pregnancy and breastfeeding.
- Abnormal uterine bleeding from the vagina of unclear etiology within 12 months before the screening stage.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Femoston® 1, Femoston® 2Femoston® 1 (1 mg estradiol / 10 mg dydrogesterone), Femoston® 2 (2 mg estradiol / 10 mg dydrogesterone) | Drug | Fixed-dose Combination (FDC) estradiol / dydrogesterone |
| DuphastonDuphaston®, 10 mg | Drug | Combination therapy with estradiol and dydrogesterone |
| KlimadynonCimicifuga racemosa rhizomatum extract | Drug | non-hormonal therapy |
| DivigelDivigel, 0.1% | Drug | Combination therapy with estradiol and dydrogesterone |
Primary outcome
Changes in the average number of "hot flashes" per day* as percentages according to data from the patient diary after 84 days (3 cycles) since the initiation of treatment compared to baseline (Visit 0).
Time frame: 84 days
11 secondary outcomes
The change in the total score on the Greene Climacteric Scale at the end of the therapy (364 days) compared to baseline.
Time frame: 364 days
The frequency of "hot flashes" after 84 days since the initiation of treatment.
Time frame: 84 days
Changes in the intensity of of menopausal symptoms calculated using the Menopause Rating Scale (MRS) after 84, 168, and 364 days since the treatment initiation compared to baseline (Visit 0).
Time frame: 84 days, 168 days, 364 days
Changes according to the Greene Climacteric Scale in each of the 4 subscales after 84, 168, and 364 days since the initiation of treatment compared to baseline (Visit 0).
Time frame: 84 days, 168 days, 364 days
Changes according to the "Hot Flush" Related Daily Interference Scale (HFRDIS) after 84, 168, and 364 days since the initiation of treatment compared to baseline (Visit 0).
Time frame: 84 days, 168 days, 364 days
The average treatment satisfaction score according to the Likert Scale after 84, 168, and 364 days since the initiation of treatment.
Time frame: 84 days, 168 days, 364 days
Changes in the adipose tissue according to densitometry results after 364 days of treatment compared to baseline (Visit 0).
Time frame: 364 days
Changes in the waist circumference after 364 days of treatment compared to baseline (Visit 0).
Time frame: 364 days
Changes in the bone tissue according to densitometry results after 364 days of treatment compared to baseline (Visit 0).
Time frame: 364 days
Changes in the bone resorption marker β-Cross laps after 364 days of treatment compared to baseline (Visit 0).
Time frame: 364 days
Changes in the bone formation marker (P1NP) after 364 days of treatment compared to baseline (Visit 0).
Time frame: 364 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Femoston® 1, Femoston® 2, Duphaston and Klimadynon in people with Perimenopausal Disorder and Hot Flashes, run by Scientific Research Institute of Public Health, Russian Federation at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tatiana Semykina (+79219565085, ts@publichealthinstitute.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the average number of "hot flashes" per day* as percentages according to data from the patient diary after 84 days (3 cycles) since the initiation of treatment compared to baseline (Visit 0). (time frame: 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2022.