The purpose of this study is to assess the safety \& efficacy of Brisdelle (paroxetine mesylate) Capsules 7.5 mg for treatment of vasomotor symptoms (VMS) associated with menopause.
This is 12-week, multicenter, double-blind, randomized, placebo-controlled study of Brisdelle (paroxetine mesylate) Capsules 7.5 mg and placebo capsules in subjects with moderate to severe postmenopausal VMS, defined as follows: * Moderate VMS: Sensation of heat with sweating, able to continue activity * 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
614
Subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Mean Change in Frequency of Moderate to Severe VMS From Baseline 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
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 The calculated severity score is reported below.
Time frame: Week 4 and Week 12
Clinical Meaningfulness Anchored to Patient Global Improvement (PGI-I) (%)
A patient improvement scale questionnaire was used during participant visits. The clinical meaningfulness of the observed treatment effect was demonstrated by performing the following analysis: Subjects were categorized in to 2 groups (satisfied and unsatisfied). Based on a 7 point patient global impression (PGI) questionnaire which assesses the subject improvement in VMS. Subjects were considered satisfied with their treatment if their response to the question "Compared to before starting the study medication, how would you describe your hot flushes now?" is 'Very much better' (1) or 'Much better' (2) or 'A little better' (3) and will be considered unsatisfied if their response to the same question is 'No change' (4) or 'A little worse' (5) or 'Much worse' (6) or 'Very much worse' (7). Receiver Operator Curve (ROC) analysis was performed on the combined data. Subjects who were satisfied with their treatment were considered to have a treatment effect with clinical meaningfulness
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Wilmax Clinical Research
Mobile, Alabama, United States
East Valley Family Physicians PLC
Chandler, Arizona, United States
Advanced Research Associates
Glendale, Arizona, United States
Premier Research Group Limited
Peoria, Arizona, United States
Verona Clinical Research, Inc
Tucson, Arizona, United States
NEA Baptist Women's Clinic
Jonesboro, Arkansas, United States
Grossmont Center for Clinical Research
La Mesa, California, United States
High Desert Medical Group
Lancaster, California, United States
Facey Medical Foundation
Mission Hills, California, United States
Northern California Research
Sacramento, California, United States
...and 64 more locations
Time frame: Week 4 and Week 12
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
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
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
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
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
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
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
Percentage of Patient Global Improvement (PGI) Scale Responders (%)
Percentage of PGI Responders: Subject's overall improvement in VMS from baseline assessed using the Patient Global Improvement (PGI) scale. Responders: Subjects Achieving a Score of "Very Much Better" Or "Much Better" Or "A Little Better". Non Responders: Subjects with a Score of "No Change" Or "A Little Worse" Or "Much Worse" Or "Very Much Worse". Patient Global Improvement (PGI) scale is described below: Compared to before starting study medication, how would you describe your hot flushes now? 0 = Not assessed 1. = Very much better 2. = Much better 3. = A little better 4. = No change 5. = A little worse 6. = Much worse 7. = Very much worse
Time frame: Week 4 and Week 12
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). The measure being reported below is percentage of responders who had an improvement in NRSscore at Week 4 and Week 12 compared to baseline. A responder is defined as a subject who had an improvement in the NRS score. An improvement is defined as a score ≤5 on each question.
Time frame: Week 4 and Week 12
Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score
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. The results presented below are change from baseline at Week 4 and Week 12.
Time frame: 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)
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
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
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
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
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