Menopause Related Conditions
Conditions
Brief summary
The primary objective of the clinical trial is to demonstrate superiority of BHR401 (oral micronized progesterone) versus placebo as a monotherapy for moderate to severe VMS in postmenopausal women. Three different doses of BHR-401 (200 mg, 300 mg or 400 mg) will be tested against placebo in hierarchical order, starting with the highest dose. Superiority will be defined as a significant (significance level α = 0.05) reduction of moderate to severe VMS frequency compared to placebo at treatment week 12 (the primary efficacy endpoint of the study).
Interventions
DRUGProgesterone oral capsule
Oral capsule treatment
DRUGPlacebo oral capsule
Oral capsule treatment
Sponsors
BHR Pharma, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blind, placebo controlled
Intervention model description
Placebo controlled parallel arm study for 12 weeks
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent * Adult (≥ 18 years), postmenopausal women, where postmenopause is defined as * at least 12 months of spontaneous amenorrhea, or * 6 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) levels \> 40 mIU/ml, or * status at least 6 weeks after bilateral oophorectomy with or without hysterectomy * Non-smoker * Mammography without pathological findings obtained within routine medical care no longer than 12 months prior to screening visit * Cervical smear (Papanicolaou test) without pathological findings (i.e. \< III) obtained no longer than 12 months prior to screening visit * In addition subjects need to fulfil the following criterion in order to be randomized (i.e. to enter the treatment period): * A minimum of 50 moderate to severe VMS episodes over the last 7 consecutive days prior to the baseline visit, as documented in the patient diary.
Exclusion criteria
* Use of any hormone replacement therapy (including phytoestrogens and other plant-derived sex hormones) during the previous 12 weeks prior to screening * Ongoing or suspicion of any estrogen-dependent malignancy. * Endometrial thickness ≥ 5 mm at screening visit * Any history or current presence or suspicion of breast cancer, including carcinoma in situ and other pre-cancerous conditions * Active malignant disease of any organ system (except for basal localized basal cell carcinoma of the skin) or history thereof in the last 5 years prior to screening visit * Vaginal bleeding due to unidentified reason within 6 weeks prior to screening * Ongoing venous thromboembolic event or history thereof within 12 months prior to screening visit * Known severe renal insufficiency (defined as glomerular filtration rate, GFR \< 30 mg/min/1.73 m²) at screening visit * Known lipid metabolism disturbances of genetic origin (e.g. familial hypercholesterolemia, familial hypertriglyceridemia) * Acute or chronic liver diseases or a history of liver disease with liver enzymes having not normalized since then * Severe disturbances of hepatic function (including porphyria), hepatic tumors, also in medical history * Rotor syndrome or Dubin-Johnson syndrome * History of icterus or generalized pruritus during a previous pregnancy * History of myocardial infarction, stroke or transient ischemic attack or severe cardiac disease, including symptomatic chronic heart failure * Ongoing major depression * Subjects who currently take or are planned to commence treatment with SSRI, SNRI for any reason during the course of the study * Diabetes mellitus * Hypersensitivity to progesterone or excipients (e.g. soy) of the study medication * Medical history of HIV infection * Concomitant diseases or therapies that may cause VMS or affect VMS frequency or severity, e.g. but not limited to poorly controlled thyroid dysfunction (thyroid medication should be stable for at least 12 weeks prior to screening and TSH levels should be within range), fear disorders (e.g. panic disorders) * Participation in a clinical trial or intake of any investigational medicinal product within three months prior to screening visit * Previous participation in this clinical trial * Known or suspected drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of moderate to severe vasomotor symptoms at 12 weeks | 12 weeks | the change vs. baseline of the frequency of moderate or severe VMS episodes (per day) after 12 weeks of treatment with BHR-401or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of moderate to severe vasomotor symptoms at 4 weeks | 4 weeks | the change vs. baseline of the frequency of moderate or severe VMS episodes (per day) |
| Severity of vasomotor symptoms at 12 weeks | 12 weeks | the change vs. baseline of the secerity of moderate or severe VMS episodes (per day) |
| Severity of vasomotor symptoms at 4 weeks | 4 weeks | the change vs. baseline of the severity of moderate or severe VMS episodes (per day) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Kupperman Index | 4 and 12 weeks | Change vs. baseline of postmenopausal symptoms as assessed by the physician by means of the Kupperman Index inventory after 4 weeks and 12 weeks of treatment |
| Sleep quality assessed by means of the Pittsburgh Sleep Quality Index (PSQI) | 4 and 12 weeks | Change in subjective sleep quality vs. baseline as assessed by means of the Pittsburgh Sleep Quality Index (PSQI) after 4 weeks and 12 weeks of treatment |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | 12 weeks | — |
Countries
Germany
Outcome results
None listed