Hot Flashes
Conditions
Keywords
Vasomotor Symptoms, Menopause, Hot Flashes, Perimenopause, Nonhormonal therapies, Climacteric symptoms, Mesafem, Low-Dose Mesylate salt of Paroxetine (LDMP)
Brief summary
To assess the safety and efficacy of Brisdelle (paroxetine mesylate) Capsules 7.5 mg for treatment of vasomotor symptoms (VMS) associated with menopause
Detailed description
The study is a 24-week, multicenter, double-blind, randomized, placebo-controlled study of Brisdelle (paroxetine mesylate) Capsules 7.5 mg in subjects with moderate to severe postmenopausal VMS, defined as follows: 1. Moderate VMS: Sensation of heat with sweating, able to continue activity 2. Severe VMS: Sensation of heat with sweating, causing cessation of activity The study is comprised of a screening period, a run-in period, a baseline visit, and a double-blind treatment period.
Interventions
Eligible subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo capsules in a 1:1 ratio.
DRUGPlacebo capsules
Eligible subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo capsules in a 1:1 ratio.
Sponsors
Noven Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female, \>40 years of age 2. Reported more than 7-8 moderate to severe hot flashes per day (average) or 50-60 moderate to severe hot flashes per week for at least 30 days prior 3. Spontaneous amenorrhea for at least 12 consecutive months 4. Amenorrhea for at least 6 months and meet the biochemical criteria for menopause 5. Bilateral salpingo-oophorectomy \>6 weeks with or without hysterectomy
Exclusion criteria
1. BMI ≥ 40 kg/m² 2. Known non-responder to previous Selective serotonin reuptake inhibitor (SSRI) or Serotonin norepinephrine reuptake inhibitor (SNRI) treatment for VMS 3. History of self-injurious behavior 4. History of clinical diagnosis of depression; or treatment for depression 5. History of clinical diagnosis of borderline personality disorder 6. Use of an investigational study medication within 30 days prior to screening or during the study 7. Concurrent participation in another clinical trial or previous participation in this trial 8. Family of investigational-site staff
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12. | Week 4 and Week 12 | Subjects recorded the number of hot flashes per week using an electronic diary. The results reported are not hot flashes per week. The results reported are: * Mean Baseline frequency of moderate to severe VMS * Mean change in frequency of moderate to severe VMS from baseline to Week 4 * Mean change in frequency of moderate to severe VMS from baseline to Week 12 |
| Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12. | Week 4 and Week 12 | Subjects recorded the number of hot flashes per week using an electronic diary. Severity score for hot flashes for each subject was calculated as the sum of 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of moderate and severe hot flashes. Weekly Severity Score = (2•Fm +3•FS)/(Fm + FS) Daily Severity Score = {(2•F) m +3•FS)/(Fm + FS)}/7 Where, Fm= Frequency of Moderate Hot Flashes Fs = Frequency of Severe Hot Flashes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median | Week 4 and Week 12 | Participants completed a electronic diary to report nightime awakenings. Subjects took study drug once daily at bedtime and they were instructed to complete daily hot flash and sleep diaries to record the number of hot flashes daily, the severity of each episode of hot flash and total number of awakenings due to hot flashes. The diary data was used to evaluate and compare the treatment groups, on the change from baseline to Week 4 and Week 12, in the total number of awakenings due to hot flashes. The total number of awakenings due to hot flashes in the run-in period was used as baseline. |
| Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 4 and Week 12 | Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI ≥32 kg/m2 subgroup, the mean weekly reduction in frequency of moderate to severe hot flashes from Baseline was calculated for Week 4 and Week 12. |
| Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median | Week 4 and Week 12 | Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI \<32 kg/m2 subgroup, the mean weekly reduction in the severity of moderate to severe hot flashes from Baseline was calculated at Week 4 and Week 12. Subjects recorded the number of hot flashes per week using an electronic diary. Severity score for hot flashes for each subject was calculated as the sum of 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of moderate and severe hot flashes. Weekly Severity Score = (2•Fm +3•FS)/(Fm + FS) Daily Severity Score = {(2•F) m +3•FS)/(Fm + FS)}/7 Where, Fm= Frequency of Moderate Hot Flashes Fs = Frequency of Severe Hot Flashes The calculated severity score is reported below. |
| Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 4 and Week 12 | Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI ≥32 kg/m2 subgroup, the mean weekly reduction in the severity of moderate to severe hot flashes from Baseline was calculated at Week 4 and Week 12. Subjects recorded the number of hot flashes per week using an electronic diary. Severity score for hot flashes for each subject was calculated as the sum of 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of moderate and severe hot flashes. Weekly Severity Score = (2•Fm +3•FS)/(Fm + FS) Daily Severity Score = {(2•F) m +3•FS)/(Fm + FS)}/7 Where, Fm= Frequency of Moderate Hot Flashes Fs = Frequency of Severe Hot Flashes The calculated severity score is reported below. |
| Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median | Week 4 and Week 12 | The Greene Climacteric Scale (GCS) was used for this measurement. The scale has 21 questions and measures symptoms in 4 areas; these are psychological (anxiety and depression), physical, vasomotor, and libido. The severity of the symptom was scored as: 0=none, 1=mild, 2=moderate, and 3=severe. Anxiety was determined by using the sum of scores 1 to 6, and depression was determined by using the sum of scores 7 to 11. Physical aspects were determined by using the sum of scores 12 to 18; vasomotor aspects were determined by using the sum of scores 19 to 20; and libido was determined by using the score for question 21. The total GCS score ranges from 0 to 63 which is the sum of all the scores for the 21-symptom assessment questions in this scale. Each subject's total GCS score at baseline and at Week 4 and Week 12 were used to calculate change from baseline in these symptoms. The change from baseline is reported below. |
| Percentage of Responders | Week 4 and Week 12 | Participants reported the number of hot flashes using an electronic diary. Participants who hd a ≥50% reduction in hot flash frequency were defined as responders. The percent of responders is presented below. |
| Percent Persistence of Benefit, Statistically Significant Difference in Having 50% or More Reduction Compared to Baseline at Week 24. | Week 24 | Persistence of treatment benefit to 24 weeks post treatment was assessed by using the following responder analysis. Responders were defined as those subjects who achieved ≥ 50% reduction from baseline in moderate to severe hot-flash frequency at Week 24; the percent change in hot flash frequency is calculated using the formula: Percent reduction at week 24 = \[(number of moderate to severe hot flash frequency at baseline - number of moderate to severe hot flash frequency at week 24) / number of moderate to severe hot flash frequency at baseline \]\*100%. |
| Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median | Week 4 and Week 12 | The Arizona Sexual Experiences Scale (ASEX) is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.The sum of the scores for all 5 items was calculated at Week 4 and Week 12. |
| Effect of Paroxetine Mesylate Capsules on Percent Improvement of Hot Flash Interference From Baseline at Week 4 and Week 12, Hot Flash Related Daily Interference Scale (HFRDIS) | Week 4 and Week 12 | Interference of hot flashes was measured by using the hot flash-related daily interference scale (HFRDIS). The HFRDIS is a 10-item scale that measures the degree to which hot flashes interfere with 9 daily activities and the tenth item measures the degree to which hot flashes interfere with each of the other items. Subjects can score for each item on a scale from 0 to 10 where 0 = Do not interfere and a score of 10 = Completely interferes. The measure being reported below is percentage of responders who had an improvement in HFRDIS score at Week 4 and Week 12 compared to baseline. A responder is defined as a subject who had an improvement in the HFRDIS score. An improvement is defined as a score ≤3 on each question. |
| Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale. | Week 4 and Week 12 | Proportion of NRS Responders: Subject's overall improvement in VMS from Baseline was assessed using the Numerical Rating Scale (NRS) The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. Responders: Subjects Achieving a Score of Very Much Improved Or Much Improved Or Minimally Improved. Non Responders: Subjects with a Score of No Change Or Minimally Worse Or Much Worse Or Very Much Worse. |
| Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression | Week 4 and Week 12 | Depression & anxiety were measured by using the Hospital Anxiety & Depression Scale (HADS). The HADS was developed to assess anxiety & depression. It is meant to differentiate symptoms of depression with those of anxiety. Number of items: 14 (7 questions relating to anxiety; 7 questions relating to depression). Responses are based on the relative frequency of symptoms over the past week, using a four point scale ranging from 0 (not at all) to 3 (very often indeed). Responses are summed to provide separate scores for anxiety and depression symptomology with possible scores ranging from 0 to 21 for each scale. The results presented below are the percentage of participants with abnormal HADS Scores for both Abnormal Anxiety & Abnormal Depression at Week 4 and Week 12. |
| Assessment of Mood | Week 4 and Week 12 | Mood was measured by using the Profile of Mood States (POMS) questionnaire. The Profile of Moods States (POMS) is a 65-item multi-dimensional measure that provides a method of assessing transient, fluctuating active mood states. Key areas that are measured include: tension-anxiety, anger-hostility, fatigue-inertia, depression-dejection, vigor-activity, confusion-bewilderment. Responses to questions are scored with the following numerical values: Not at all = 1, A little = 2, Moderate = 3, Quite a bit = 4, Extremely = 5. A total score for a domain was obtained by summing the responses of individual items in the domain. The total POMS score can range from 65 to 325. Each subject's total POMS score at baseline and at Week 4 and Week 12 were used to calculate the percent of participants with less disturbance in mood at Week 4 and Week 12 compared to baseline. The percent of participants with less disturbance in mood is reported below. |
| BMI Change From Baseline (kg/m2), Median | Week 4 and Week 12 | Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. Assessment of the effect of Brisdelle compared with placebo on body mass index. |
| Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS) | Week 4 and Week 12 | Subject's overall improvement in VMS from Baseline assessed using the Numerical Rating Scale (NRS) The NRS is measured on a scale of 0 to 10 on how bothered the subject was by her VMS (0=not bothered at all and 10=very much bothered). Responders: Subjects with NRS Score of 5 Or Less. Non-Responders: Subjects With NRS Score of Greater than Or Equal to 6. |
| Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median | Week 4 and Week 12 | Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI \<32 kg/m2 subgroup, the mean weekly reduction in frequency of moderate to severe hot flashes from Baseline was calculated for Week 4 and Week 12. |
Countries
United States
Participant flow
Recruitment details
24-week, multicenter, double-blind, randomized, placebo-controlled study of Brisdelle (paroxetine mesylate) Capsules in subjects with moderate to severe postmenopausal vasomotor symptoms. Locations: Medical Clinics
Participants by arm
| Arm | Count |
|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules Experimental
Eligible subjects were randomized to receive either Brisdelle (paroxetine mesylate) Capsules or placebo capsules in a 1:1 ratio. | 285 |
| Placebo Capsules Eligible subjects were randomized to receive either Brisdelle (paroxetine mesylate) Capsules or placebo capsules in a 1:1 ratio. | 285 |
| Total | 570 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 15 |
| Overall Study | Eligibility Criteria | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 9 | 3 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Suicidality Tracking Scale | 3 | 1 |
| Overall Study | Withdrawal by Subject | 21 | 40 |
Baseline characteristics
| Characteristic | Placebo Capsules | Brisdelle (Paroxetine Mesylate) Capsules | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 16 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 267 Participants | 269 Participants | 536 Participants |
| Age, Continuous | 54.5 years STANDARD_DEVIATION 5.74 | 54.2 years STANDARD_DEVIATION 5.47 | 54.4 years STANDARD_DEVIATION 5.6 |
| Region of Enrollment United States | 285 participants | 285 participants | 570 participants |
| Sex: Female, Male Female | 285 Participants | 285 Participants | 570 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 161 / 285 | 146 / 285 |
| serious Total, serious adverse events | 13 / 285 | 7 / 285 |
Outcome results
Primary
Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12.
Subjects recorded the number of hot flashes per week using an electronic diary. The results reported are not hot flashes per week. The results reported are: * Mean Baseline frequency of moderate to severe VMS * Mean change in frequency of moderate to severe VMS from baseline to Week 4 * Mean change in frequency of moderate to severe VMS from baseline to Week 12
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12. | Baseline | 10.83 Hot flashes per day | Standard Deviation 3.86 |
| Brisdelle (Paroxetine Mesylate) Capsules | Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12. | Week 4 | -4.13 Hot flashes per day | Standard Deviation 4.02 |
| Brisdelle (Paroxetine Mesylate) Capsules | Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12. | Week 12 | -5.31 Hot flashes per day | Standard Deviation 4.67 |
| Placebo Capsules | Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12. | Baseline | 10.90 Hot flashes per day | Standard Deviation 3.96 |
| Placebo Capsules | Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12. | Week 4 | -2.71 Hot flashes per day | Standard Deviation 4.31 |
| Placebo Capsules | Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12. | Week 12 | -3.94 Hot flashes per day | Standard Deviation 5.13 |
p-value: <0.0001Rank transformed ANCOVA
p-value: 0.0001Rank transformed ANCOVA
Primary
Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12.
Subjects recorded the number of hot flashes per week using an electronic diary. Severity score for hot flashes for each subject was calculated as the sum of 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of moderate and severe hot flashes. Weekly Severity Score = (2•Fm +3•FS)/(Fm + FS) Daily Severity Score = {(2•F) m +3•FS)/(Fm + FS)}/7 Where, Fm= Frequency of Moderate Hot Flashes Fs = Frequency of Severe Hot Flashes
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12. | Baseline | 2.525 Hot Flash Severity Score per day | Standard Deviation 0.3 |
| Brisdelle (Paroxetine Mesylate) Capsules | Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12. | Week 4 | -0.092 Hot Flash Severity Score per day | Standard Deviation 0.24 |
| Brisdelle (Paroxetine Mesylate) Capsules | Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12. | Week 12 | -0.0126 Hot Flash Severity Score per day | Standard Deviation 0.31 |
| Placebo Capsules | Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12. | Baseline | 2.532 Hot Flash Severity Score per day | Standard Deviation 0.32 |
| Placebo Capsules | Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12. | Week 4 | -0.059 Hot Flash Severity Score per day | Standard Deviation 0.22 |
| Placebo Capsules | Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12. | Week 12 | -0.066 Hot Flash Severity Score per day | Standard Deviation 0.26 |
p-value: 0.0368Rank transformed ANCOVA
p-value: 0.0064Rank transformed ANCOVA
Secondary
Assessment of Mood
Mood was measured by using the Profile of Mood States (POMS) questionnaire. The Profile of Moods States (POMS) is a 65-item multi-dimensional measure that provides a method of assessing transient, fluctuating active mood states. Key areas that are measured include: tension-anxiety, anger-hostility, fatigue-inertia, depression-dejection, vigor-activity, confusion-bewilderment. Responses to questions are scored with the following numerical values: Not at all = 1, A little = 2, Moderate = 3, Quite a bit = 4, Extremely = 5. A total score for a domain was obtained by summing the responses of individual items in the domain. The total POMS score can range from 65 to 325. Each subject's total POMS score at baseline and at Week 4 and Week 12 were used to calculate the percent of participants with less disturbance in mood at Week 4 and Week 12 compared to baseline. The percent of participants with less disturbance in mood is reported below.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Assessment of Mood | Week 4 | 37.40 Percent of participants |
| Brisdelle (Paroxetine Mesylate) Capsules | Assessment of Mood | Week 12 | 37.16 Percent of participants |
| Placebo Capsules | Assessment of Mood | Week 4 | 42.39 Percent of participants |
| Placebo Capsules | Assessment of Mood | Week 12 | 44.23 Percent of participants |
Secondary
BMI Change From Baseline (kg/m2), Median
Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. Assessment of the effect of Brisdelle compared with placebo on body mass index.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | BMI Change From Baseline (kg/m2), Median | Week 4 | 0.00 kg/m2 |
| Brisdelle (Paroxetine Mesylate) Capsules | BMI Change From Baseline (kg/m2), Median | Week 12 | 0.15 kg/m2 |
| Placebo Capsules | BMI Change From Baseline (kg/m2), Median | Week 4 | 0.08 kg/m2 |
| Placebo Capsules | BMI Change From Baseline (kg/m2), Median | Week 12 | 0.11 kg/m2 |
Secondary
Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median
The Arizona Sexual Experiences Scale (ASEX) is a 5-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.The sum of the scores for all 5 items was calculated at Week 4 and Week 12.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median | Week 4 | 0.00 Units on a scale |
| Brisdelle (Paroxetine Mesylate) Capsules | Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median | Week 12 | 0.00 Units on a scale |
| Placebo Capsules | Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median | Week 12 | 0.00 Units on a scale |
| Placebo Capsules | Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median | Week 4 | 0.00 Units on a scale |
Secondary
Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median
The Greene Climacteric Scale (GCS) was used for this measurement. The scale has 21 questions and measures symptoms in 4 areas; these are psychological (anxiety and depression), physical, vasomotor, and libido. The severity of the symptom was scored as: 0=none, 1=mild, 2=moderate, and 3=severe. Anxiety was determined by using the sum of scores 1 to 6, and depression was determined by using the sum of scores 7 to 11. Physical aspects were determined by using the sum of scores 12 to 18; vasomotor aspects were determined by using the sum of scores 19 to 20; and libido was determined by using the score for question 21. The total GCS score ranges from 0 to 63 which is the sum of all the scores for the 21-symptom assessment questions in this scale. Each subject's total GCS score at baseline and at Week 4 and Week 12 were used to calculate change from baseline in these symptoms. The change from baseline is reported below.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median | Week 4 | -3.00 units on a scale |
| Brisdelle (Paroxetine Mesylate) Capsules | Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median | Week 12 | -4.00 units on a scale |
| Placebo Capsules | Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median | Week 4 | -3.00 units on a scale |
| Placebo Capsules | Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median | Week 12 | -3.00 units on a scale |
Secondary
Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median
Participants completed a electronic diary to report nightime awakenings. Subjects took study drug once daily at bedtime and they were instructed to complete daily hot flash and sleep diaries to record the number of hot flashes daily, the severity of each episode of hot flash and total number of awakenings due to hot flashes. The diary data was used to evaluate and compare the treatment groups, on the change from baseline to Week 4 and Week 12, in the total number of awakenings due to hot flashes. The total number of awakenings due to hot flashes in the run-in period was used as baseline.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median | Week 4 | -8.50 Awakenings |
| Brisdelle (Paroxetine Mesylate) Capsules | Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median | Week 12 | -13.15 Awakenings |
| Placebo Capsules | Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median | Week 4 | -6.62 Awakenings |
| Placebo Capsules | Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median | Week 12 | -8.67 Awakenings |
Secondary
Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median
Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI \<32 kg/m2 subgroup, the mean weekly reduction in frequency of moderate to severe hot flashes from Baseline was calculated for Week 4 and Week 12.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median | Week 4 | -28.50 Hot flashes per week |
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median | Week 12 | -41.00 Hot flashes per week |
| Placebo Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median | Week 4 | -18.0 Hot flashes per week |
| Placebo Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median | Week 12 | -27.00 Hot flashes per week |
Secondary
Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median
Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI ≥32 kg/m2 subgroup, the mean weekly reduction in frequency of moderate to severe hot flashes from Baseline was calculated for Week 4 and Week 12.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 4 | -22.0 Hot flashes per week |
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 12 | -31.50 Hot flashes per week |
| Placebo Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 4 | -17.0 Hot flashes per week |
| Placebo Capsules | Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 12 | -23.00 Hot flashes per week |
Secondary
Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median
Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI \<32 kg/m2 subgroup, the mean weekly reduction in the severity of moderate to severe hot flashes from Baseline was calculated at Week 4 and Week 12. Subjects recorded the number of hot flashes per week using an electronic diary. Severity score for hot flashes for each subject was calculated as the sum of 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of moderate and severe hot flashes. Weekly Severity Score = (2•Fm +3•FS)/(Fm + FS) Daily Severity Score = {(2•F) m +3•FS)/(Fm + FS)}/7 Where, Fm= Frequency of Moderate Hot Flashes Fs = Frequency of Severe Hot Flashes The calculated severity score is reported below.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median | Week 4 | -0.033 Hot Flash Severity scores per week |
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median | Week 12 | -0.045 Hot Flash Severity scores per week |
| Placebo Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median | Week 4 | -0.004 Hot Flash Severity scores per week |
| Placebo Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median | Week 12 | -0.00 Hot Flash Severity scores per week |
Secondary
Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median
Subjects were weighed at each clinic visit and reported the number of hot flashes using an electronic diary. For the BMI ≥32 kg/m2 subgroup, the mean weekly reduction in the severity of moderate to severe hot flashes from Baseline was calculated at Week 4 and Week 12. Subjects recorded the number of hot flashes per week using an electronic diary. Severity score for hot flashes for each subject was calculated as the sum of 2 times the number of moderate hot flashes, plus 3 times the number of severe hot flashes, divided by the total number of moderate and severe hot flashes. Weekly Severity Score = (2•Fm +3•FS)/(Fm + FS) Daily Severity Score = {(2•F) m +3•FS)/(Fm + FS)}/7 Where, Fm= Frequency of Moderate Hot Flashes Fs = Frequency of Severe Hot Flashes The calculated severity score is reported below.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 4 | -0.039 Hot Flash Severity scores per week |
| Brisdelle (Paroxetine Mesylate) Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 12 | -0.052 Hot Flash Severity scores per week |
| Placebo Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 4 | -0.036 Hot Flash Severity scores per week |
| Placebo Capsules | Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median | Week 12 | -0.051 Hot Flash Severity scores per week |
Secondary
Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression
Depression & anxiety were measured by using the Hospital Anxiety & Depression Scale (HADS). The HADS was developed to assess anxiety & depression. It is meant to differentiate symptoms of depression with those of anxiety. Number of items: 14 (7 questions relating to anxiety; 7 questions relating to depression). Responses are based on the relative frequency of symptoms over the past week, using a four point scale ranging from 0 (not at all) to 3 (very often indeed). Responses are summed to provide separate scores for anxiety and depression symptomology with possible scores ranging from 0 to 21 for each scale. The results presented below are the percentage of participants with abnormal HADS Scores for both Abnormal Anxiety & Abnormal Depression at Week 4 and Week 12.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression | Week 4 | 5.65 Percentage of participants |
| Brisdelle (Paroxetine Mesylate) Capsules | Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression | Week 12 | 4.13 Percentage of participants |
| Placebo Capsules | Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression | Week 4 | 2.44 Percentage of participants |
| Placebo Capsules | Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression | Week 12 | 5.24 Percentage of participants |
Secondary
Effect of Paroxetine Mesylate Capsules on Percent Improvement of Hot Flash Interference From Baseline at Week 4 and Week 12, Hot Flash Related Daily Interference Scale (HFRDIS)
Interference of hot flashes was measured by using the hot flash-related daily interference scale (HFRDIS). The HFRDIS is a 10-item scale that measures the degree to which hot flashes interfere with 9 daily activities and the tenth item measures the degree to which hot flashes interfere with each of the other items. Subjects can score for each item on a scale from 0 to 10 where 0 = Do not interfere and a score of 10 = Completely interferes. The measure being reported below is percentage of responders who had an improvement in HFRDIS score at Week 4 and Week 12 compared to baseline. A responder is defined as a subject who had an improvement in the HFRDIS score. An improvement is defined as a score ≤3 on each question.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Effect of Paroxetine Mesylate Capsules on Percent Improvement of Hot Flash Interference From Baseline at Week 4 and Week 12, Hot Flash Related Daily Interference Scale (HFRDIS) | Week 4 | 26.03 Percent of participants |
| Brisdelle (Paroxetine Mesylate) Capsules | Effect of Paroxetine Mesylate Capsules on Percent Improvement of Hot Flash Interference From Baseline at Week 4 and Week 12, Hot Flash Related Daily Interference Scale (HFRDIS) | Week 12 | 15.89 Percent of participants |
| Placebo Capsules | Effect of Paroxetine Mesylate Capsules on Percent Improvement of Hot Flash Interference From Baseline at Week 4 and Week 12, Hot Flash Related Daily Interference Scale (HFRDIS) | Week 4 | 30.51 Percent of participants |
| Placebo Capsules | Effect of Paroxetine Mesylate Capsules on Percent Improvement of Hot Flash Interference From Baseline at Week 4 and Week 12, Hot Flash Related Daily Interference Scale (HFRDIS) | Week 12 | 21.32 Percent of participants |
Secondary
Percentage of Responders
Participants reported the number of hot flashes using an electronic diary. Participants who hd a ≥50% reduction in hot flash frequency were defined as responders. The percent of responders is presented below.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Percentage of Responders | Week 4 | 35.56 percentage of participants |
| Brisdelle (Paroxetine Mesylate) Capsules | Percentage of Responders | Week 12 | 49.30 percentage of participants |
| Placebo Capsules | Percentage of Responders | Week 4 | 25.35 percentage of participants |
| Placebo Capsules | Percentage of Responders | Week 12 | 33.80 percentage of participants |
Secondary
Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS)
Subject's overall improvement in VMS from Baseline assessed using the Numerical Rating Scale (NRS) The NRS is measured on a scale of 0 to 10 on how bothered the subject was by her VMS (0=not bothered at all and 10=very much bothered). Responders: Subjects with NRS Score of 5 Or Less. Non-Responders: Subjects With NRS Score of Greater than Or Equal to 6.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS) | Week 4 | 35.48 percentage of total number of subjects |
| Brisdelle (Paroxetine Mesylate) Capsules | Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS) | Week 12 | 46.62 percentage of total number of subjects |
| Placebo Capsules | Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS) | Week 12 | 37.72 percentage of total number of subjects |
| Placebo Capsules | Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS) | Week 4 | 25.27 percentage of total number of subjects |
Secondary
Percent Persistence of Benefit, Statistically Significant Difference in Having 50% or More Reduction Compared to Baseline at Week 24.
Persistence of treatment benefit to 24 weeks post treatment was assessed by using the following responder analysis. Responders were defined as those subjects who achieved ≥ 50% reduction from baseline in moderate to severe hot-flash frequency at Week 24; the percent change in hot flash frequency is calculated using the formula: Percent reduction at week 24 = \[(number of moderate to severe hot flash frequency at baseline - number of moderate to severe hot flash frequency at week 24) / number of moderate to severe hot flash frequency at baseline \]\*100%.
Time frame: Week 24
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Percent Persistence of Benefit, Statistically Significant Difference in Having 50% or More Reduction Compared to Baseline at Week 24. | 47.54 percentage of total number of subjects |
| Placebo Capsules | Percent Persistence of Benefit, Statistically Significant Difference in Having 50% or More Reduction Compared to Baseline at Week 24. | 36.27 percentage of total number of subjects |
p-value: 0.0066Logit model
Secondary
Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale.
Proportion of NRS Responders: Subject's overall improvement in VMS from Baseline was assessed using the Numerical Rating Scale (NRS) The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. Responders: Subjects Achieving a Score of Very Much Improved Or Much Improved Or Minimally Improved. Non Responders: Subjects with a Score of No Change Or Minimally Worse Or Much Worse Or Very Much Worse.
Time frame: Week 4 and Week 12
Population: The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Brisdelle (Paroxetine Mesylate) Capsules | Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale. | Week 4 | 67.88 percentage of participants |
| Brisdelle (Paroxetine Mesylate) Capsules | Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale. | Week 12 | 69.88 percentage of participants |
| Placebo Capsules | Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale. | Week 4 | 53.58 percentage of participants |
| Placebo Capsules | Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale. | Week 12 | 59.74 percentage of participants |