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Sponsor's Decision
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The primary objective of this study was to determine the clinical safety of RAD1901 and to evaluate whether RAD1901 reduced the frequency and severity of moderate to severe vasomotor symptoms (VMS; "hot flashes") in postmenopausal women.
This was a Phase 2b outpatient, prospective, multicenter, double-blind, randomized, placebo-controlled study to determine whether elacestrant reduces the frequency and severity of vasomotor symptoms (VMS; "hot flashes") in postmenopausal women with moderate to severe hot flashes. Postmenopausal women who met study criteria were followed for 12 weeks on double-blind study medication and two weeks off study medication.
Treatment was randomized 1:1:1:1 to ensure that an approximately equal number of patients were exposed to each of three RAD1901 (elacestrant) doses (5, 10 and 20 mg/day) or placebo. The total period of placebo exposure was 14 weeks.
Enrolling approximately 300 patients was expected to provide power for testing superiority of the primary efficacy endpoint outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regimen 1 | Experimental | RAD1901 5 mg/day |
|
| Regimen 2 | Experimental | RAD1901 10 mg/day |
|
| Regimen 3 | Experimental | RAD1901 20 mg/day |
|
| Regimen 4 | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RAD1901 | Drug | RAD1901 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12 in the Frequency of Moderate to Severe Hot Flashes | Change from baseline to week 12 in the average number of moderate and severe hot flashes per day, where change is calculated as week 12 minus baseline so that negative values indicate a reduction (improvement) of hot flash frequency. Severity of hot flashes was self-assessed and reported as follows:
| Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 4 in the Frequency of Moderate to Severe Hot Flashes | Change from baseline to week 4 in the average number of moderate and severe hot flashes per day, where change is calculated as week 4 minus baseline so that negative values indicate a reduction (improvement) of hot flash frequency. | Baseline and 4 weeks |
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Inclusion Criteria:
To have participated in this study, a subject MUST:
Exclusion Criteria:
Subjects with any of the following characteristics were not be eligible to participate in the study:
have a history of invasive breast cancer or ductal carcinoma in situ, melanoma or any gynecologic cancer.
using any of the following:
have been treated with a gonadotropin-releasing hormone (GnRH) agonist within the last year
have been treated with anti-estrogens or aromatase inhibitors within 2 months prior to study entry
have been concurrently treated and will abstain from gabapentin and paroxetine or serotonin and norepinephrine reuptake inhibitors (SNRIs) for VMS or other indications for 3 months during the trial and have not taken within 4 weeks prior to screening
have unexplained vaginal bleeding within the 3 months prior to study entry
have an endometrial biopsy at baseline with a diagnosis by a gynecologic pathologist of proliferative, hyperplasia, polyp or cancer
have unresolved cervical cytological smear report of atypical glandular or squamous cells of undetermined significance. Cervical cytologic smear report of ASCUS, low grade squamous intraepithelial lesion or greater, or any reported dysplasia
have unresolved findings suspicious for malignancy on the breast examination
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Operations | Radius Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Women's Health Care Specialists P.C. - Beyer Research | Kalamazoo | Michigan | 49009 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Regimen 1 | RAD1901 5 mg RAD1901: RAD1901 |
| FG001 | Regimen 2 | RAD1901 10 mg RAD1901: RAD1901 |
| FG002 | Regimen 3 | RAD1901 20 mg RAD1901: RAD1901 |
| FG003 | Regimen 4 | Placebo Placebo: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
mITT population
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| ID | Title | Description |
|---|---|---|
| BG000 | Regimen 1 RAD1901 5 mg | RAD1901 5 mg RAD1901: RAD1901 |
| BG001 | Regimen 2 RAD1901 10 mg | RAD1901 10 mg RAD1901: RAD1901 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Week 12 in the Frequency of Moderate to Severe Hot Flashes | Change from baseline to week 12 in the average number of moderate and severe hot flashes per day, where change is calculated as week 12 minus baseline so that negative values indicate a reduction (improvement) of hot flash frequency. Severity of hot flashes was self-assessed and reported as follows:
| The modified intent to treat (mITT) population was used. This included all patients in the safety population who had recorded hot flash data in their eDiaries for at least 5 days during baseline and for at least one day while on double-blind study medication, and was the primary analysis population for all efficacy analyses | Posted | Least Squares Mean | Standard Error | moderate to severe hot flashes per day | Baseline and 12 weeks |
|
Up to 14 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regimen 1 RAD1901 5 mg | RAD1901 5 mg RAD1901: RAD1901 | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Operations | Radius Pharmaceuticals, Inc. | 617-551-4000 | clinopsinfo@radiuspharm.com |
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| ID | Term |
|---|---|
| D019584 | Hot Flashes |
| ID | Term |
|---|---|
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000626184 | RAD1901 |
| C000626176 | elacestrant |
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| Placebo | Other | Placebo |
|
| Change From Baseline to Week 4 and Week 12 in the Severity of Hot Flashes |
Change from baseline to week 4 and week 12 in the average daily severity of hot flashes, where change is calculated as week 4 or week 12 minus baseline so that negative values indicate a reduction (improvement) of hot flash severity. Subjects recorded the number of hot flashes per day using an electronic diary. Daily severity score for hot flashes for each subject was calculated as the sum of the number of mild hot flashes, plus 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of mild, moderate, and severe hot flashes. That is, Daily Severity Score = (Fmild + 2•Fmod + 3•Fsev)/(Fmild + Fmod + Fsev) where Fmild= frequency of mild hot flashes, Fmod = frequency of moderate hot flashes, Fsev = frequency of severe hot flashes. The measure is a weighted average of the frequencies of Hot Flashes. |
| Baseline, 4 weeks, and 12 weeks |
| Change From Baseline to Week 4 and Week 12 in the Frequency of All Hot Flashes | Change from baseline to week 4 and week 12 in the average number of all hot flashes (mild, moderate, and severe) by eDiary, where change is calculated as week 4 or week 12 minus baseline so that negative values indicate a reduction (improvement) of hot flash frequency. | Baseline, 4 weeks, and 12 weeks |
| BG002 | Regimen 3 RAD1901 20 mg | RAD1901 20 mg RAD1901: RAD1901 |
| BG003 | Regimen 4 Placebo | Placebo Placebo: Placebo |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Regimen 1 |
RAD1901 5 mg RAD1901: RAD1901 |
| OG001 | Regimen 2 | RAD1901 10 mg RAD1901: RAD1901 |
| OG002 | Regimen 3 | RAD1901 20 mg RAD1901: RAD1901 |
| OG003 | Regimen 4 | Placebo Placebo: Placebo |
|
|
|
| Secondary | Change From Baseline to Week 4 in the Frequency of Moderate to Severe Hot Flashes | Change from baseline to week 4 in the average number of moderate and severe hot flashes per day, where change is calculated as week 4 minus baseline so that negative values indicate a reduction (improvement) of hot flash frequency. | mITT population | Posted | Mean | Standard Deviation | moderate to severe hot flashes per day | Baseline and 4 weeks |
|
|
|
| Secondary | Change From Baseline to Week 4 and Week 12 in the Severity of Hot Flashes | Change from baseline to week 4 and week 12 in the average daily severity of hot flashes, where change is calculated as week 4 or week 12 minus baseline so that negative values indicate a reduction (improvement) of hot flash severity. Subjects recorded the number of hot flashes per day using an electronic diary. Daily severity score for hot flashes for each subject was calculated as the sum of the number of mild hot flashes, plus 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of mild, moderate, and severe hot flashes. That is, Daily Severity Score = (Fmild + 2•Fmod + 3•Fsev)/(Fmild + Fmod + Fsev) where Fmild= frequency of mild hot flashes, Fmod = frequency of moderate hot flashes, Fsev = frequency of severe hot flashes. The measure is a weighted average of the frequencies of Hot Flashes. | mITT population | Posted | Mean | Standard Deviation | hot flash severity score per day | Baseline, 4 weeks, and 12 weeks |
|
|
|
| Secondary | Change From Baseline to Week 4 and Week 12 in the Frequency of All Hot Flashes | Change from baseline to week 4 and week 12 in the average number of all hot flashes (mild, moderate, and severe) by eDiary, where change is calculated as week 4 or week 12 minus baseline so that negative values indicate a reduction (improvement) of hot flash frequency. | mITT population | Posted | Mean | Standard Deviation | hot flashes per day | Baseline, 4 weeks, and 12 weeks |
|
|
|
| 38 |
| 0 |
| 38 |
| 11 |
| 38 |
| EG001 | Regimen 2 RAD1901 10 mg | RAD1901 10 mg RAD1901: RAD1901 | 0 | 34 | 0 | 34 | 3 | 34 |
| EG002 | Regimen 3 RAD1901 20 mg | RAD1901 20 mg RAD1901: RAD1901 | 0 | 29 | 0 | 29 | 7 | 29 |
| EG003 | Regimen 4 Placebo | Placebo Placebo: Placebo | 0 | 38 | 0 | 38 | 13 | 38 |
| Diarrhoea | Gastrointestinal disorders | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | Non-systematic Assessment |
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| Sinusitis | Infections and infestations | Non-systematic Assessment |
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| Vaginal haemorrhage | Reproductive system and breast disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | Non-systematic Assessment |
|
| Chills | General disorders | Non-systematic Assessment |
|
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| Week 12 change from baseline in severity |
|
| Week 12 change from baseline |
|