Hot Flashes
Conditions
Keywords
Postmenopause, Hot Flashes, Estradiol, Polyestradiol phosphate, Estradiol valerate, Estradiol 3-benzoate, Estradiol 17 beta-cypionate, Estrogens, Hormones, Hormones, Hormone Substitutes, Hormone Antagonists
Brief summary
Estradiol treatment is effective at reducing vasomotor symptoms (eg hot flushes) in postmenopausal women. This study will evaluate the safety and efficacy of Evamist.
Detailed description
Multicenter, randomized, double-blind, placebo-controlled trial evaluating different doses of transdermal estradiol delivered by sray to symptomatic postmenopausal women. The endpoints are the reduction in frequency and severity of hot flushes.
Interventions
DRUGEstradiol transdermal one 90 μL spray
Estradiol transdermal spray, one 90 μL spray applied to 1 inner forearm daily for 12 weeks using a blinded applicator
DRUGEstradiol transdermal spray, two 90 μL sprays
Estradiol transdermal spray, two 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator
DRUGEstradiol transdermal three 90 μL sprays
Estradiol transdermal spray, three 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator
DRUGPlacebo transdermal two 90 μL sprays
Placebo transdermal spray, two 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator
DRUGPlacebo transdermal three 90 μL sprays
Placebo transdermal spray, three 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator
DRUGPlacebo transdermal one 90 μL spray
Placebo transdermal spray, one 90 μL spray applied to 1 inner forearm daily for 12 weeks using a blinded applicator
Sponsors
Lumara Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Post menopausal women, * Ages 35 or older, * Frequent moderate to severe hot flushes, * Qualifying general medical health
Exclusion criteria
* Disqualifying gynecological disorders, * Disqualifying dermatological disorders, * Disqualifying concurrent conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day | baseline to week 12 | Patients completed a daily diary to record the number of mild, moderate and number of moderate or severe vasomotor symptoms \[hot flushes and sweating\] experienced each day. Mild, moderate and severe hot flushes and sweating were defined as follows: Mild = sensation of heat without sweating Moderate = sensation of heat with sweating, ability to continue activity Severe = sensation of heat with sweating, causing discontinuation of activity |
| Mean Change the Severity of Moderate to Severe Vasomotor Symptoms | baseline to week 12 (12 weeks) | Patients completed a daily diary to record the number of mild, moderate and severe vasomotor symptoms experienced each day. Mild, moderate and severe were defined as follows: Mild = sensation of heat without sweating Moderate = sensation of heat with sweating, ability to continue activity Severe = sensation of heat with sweating, causing discontinuation of activity Severity of hot flushes was measured on a scale of none = 0, mild = 1, moderate = 2 and severe = 3. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 43 physicians' offices, or their affiliated locations, within the United States between 17 December 2004 and 09 March 2006
Pre-assignment details
Participants underwent a four week screening period to determine eligibility prior to assignment into the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Transdermal Three 90 μL Sprays Placebo transdermal spray, three 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator | 75 |
| Placebo Transdermal Two 90 μL Sprays Placebo transdermal spray, two 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator | 76 |
| Placebo Transdermal One 90 μL Spray Placebo transdermal spray, one 90 μL spray applied to 1 inner forearm daily for 12 weeks using a blinded applicator | 77 |
| Estradiol Transdermal Three 90 μL Sprays Estradiol transdermal spray, three 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator | 76 |
| Estradiol Transdermal Two 90 μL Sprays Estradiol transdermal spray, two 90 μL spray applied to adjacent non-overlapping areas on 1 inner forearm daily for 12 weeks using a blinded applicator | 74 |
| Estradiol Transdermal One 90 μL Spray Estradiol transdermal spray, one 90 μL spray applied to 1 inner forearm daily for 12 weeks using a blinded applicator | 76 |
| Total | 454 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 2 | 2 | 2 | 2 |
| Overall Study | Hurricane Katrina | 4 | 2 | 3 | 0 | 3 | 1 |
| Overall Study | Investigator Judgement | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 1 | 1 | 2 | 4 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 3 | 0 | 1 | 1 |
| Overall Study | Subject Moved | 2 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Subject Traveling Out of Country | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Unavailable due to husband's illness | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 9 | 2 | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo Transdermal Three 90 μL Sprays | Placebo Transdermal Two 90 μL Sprays | Placebo Transdermal One 90 μL Spray | Estradiol Transdermal Three 90 μL Sprays | Estradiol Transdermal Two 90 μL Sprays | Estradiol Transdermal One 90 μL Spray | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 52.0 years STANDARD_DEVIATION 6.3 | 52.0 years STANDARD_DEVIATION 7 | 52.8 years STANDARD_DEVIATION 6.9 | 52.3 years STANDARD_DEVIATION 5.7 | 52.2 years STANDARD_DEVIATION 6.8 | 53.5 years STANDARD_DEVIATION 6.8 | 52.7 years STANDARD_DEVIATION 6.5 |
| Sex: Female, Male Female | 75 Participants | 76 Participants | 77 Participants | 76 Participants | 74 Participants | 76 Participants | 454 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 75 | 18 / 76 | 12 / 77 | 21 / 76 | 29 / 74 | 21 / 76 |
| serious Total, serious adverse events | 0 / 75 | 0 / 76 | 1 / 77 | 3 / 76 | 1 / 74 | 3 / 76 |
Outcome results
Primary
Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day
Patients completed a daily diary to record the number of mild, moderate and number of moderate or severe vasomotor symptoms \[hot flushes and sweating\] experienced each day. Mild, moderate and severe hot flushes and sweating were defined as follows: Mild = sensation of heat without sweating Moderate = sensation of heat with sweating, ability to continue activity Severe = sensation of heat with sweating, causing discontinuation of activity
Time frame: baseline to week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Transdermal Three 90 μL Sprays | Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day | -5.32 Vasomotor symptoms per day | Standard Deviation 6.3 |
| Placebo Transdermal Two 90 μL Sprays | Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day | -6.19 Vasomotor symptoms per day | Standard Deviation 5.77 |
| Placebo Transdermal One 90 μL Spray | Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day | -4.76 Vasomotor symptoms per day | Standard Deviation 5.84 |
| Estradiol Transdermal Three 90 μL Sprays | Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day | -8.44 Vasomotor symptoms per day | Standard Deviation 4.5 |
| Estradiol Transdermal Two 90 μL Sprays | Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day | -8.66 Vasomotor symptoms per day | Standard Deviation 6.65 |
| Estradiol Transdermal One 90 μL Spray | Mean Change in the Number of Moderate to Severe Vasomotor Symptoms Per Day | -8.10 Vasomotor symptoms per day | Standard Deviation 4.02 |
p-value: <0.0001ANCOVA
p-value: 0.0099ANCOVA
p-value: 0.0004ANCOVA
Primary
Mean Change the Severity of Moderate to Severe Vasomotor Symptoms
Patients completed a daily diary to record the number of mild, moderate and severe vasomotor symptoms experienced each day. Mild, moderate and severe were defined as follows: Mild = sensation of heat without sweating Moderate = sensation of heat with sweating, ability to continue activity Severe = sensation of heat with sweating, causing discontinuation of activity Severity of hot flushes was measured on a scale of none = 0, mild = 1, moderate = 2 and severe = 3.
Time frame: baseline to week 12 (12 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Transdermal Three 90 μL Sprays | Mean Change the Severity of Moderate to Severe Vasomotor Symptoms | -0.31 Scores on a scale | Standard Deviation 0.75 |
| Placebo Transdermal Two 90 μL Sprays | Mean Change the Severity of Moderate to Severe Vasomotor Symptoms | -0.54 Scores on a scale | Standard Deviation 0.89 |
| Placebo Transdermal One 90 μL Spray | Mean Change the Severity of Moderate to Severe Vasomotor Symptoms | -0.26 Scores on a scale | Standard Deviation 0.6 |
| Estradiol Transdermal Three 90 μL Sprays | Mean Change the Severity of Moderate to Severe Vasomotor Symptoms | -1.07 Scores on a scale | Standard Deviation 1.01 |
| Estradiol Transdermal Two 90 μL Sprays | Mean Change the Severity of Moderate to Severe Vasomotor Symptoms | -0.92 Scores on a scale | Standard Deviation 1.01 |
| Estradiol Transdermal One 90 μL Spray | Mean Change the Severity of Moderate to Severe Vasomotor Symptoms | -1.04 Scores on a scale | Standard Deviation 1.01 |
p-value: <0.0001ANCOVA
p-value: 0.0406ANCOVA
p-value: <0.0001ANCOVA