Trial Outcomes & Findings for Eight-Week Efficacy & Safety Study of Brisdelle™ (Formerly Known as Mesafem) in the Treatment of Vasomotor Symptoms Associated With Menopause (NCT NCT00786188)

Recruitment Period = 29 October 2008 to 26 May 2009 Types of Locations = Research clinics

Eligible subjects were entered into a 1-week observation period followed by a 1-week run-in period. After completion of run-in period, eligible subjects were randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo in a 1:1 ratio. Study drug was administered once daily at bedtime.

Eight-Week Efficacy & Safety Study of Brisdelle™ (Formerly Known as Mesafem) in the Treatment of Vasomotor Symptoms Associated With Menopause

The number of hot flashes reported in the result table are: * 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 8. They are both measured as hot flashes per week.

A scale was not used to measure severity scores. Severity scores of hot flashes were calculated for each subject. The following formula was used to calculate severity. SS = (2•Fm + 3•Fs) ÷ (Fm + Fs) Where: SS = severity score Fm = frequency of moderate hot flashes Fs = frequency of severe hot flashes The mean number of moderate and severe hot flashes that was recorded in the Run-In Period was used to calculate the baseline severity score.

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 8 were used to calculate change from baseline in these symptoms. The change from baseline is reported below.

A scale was not used for this measurement. Composite scores of hot flashes were calculated by using the following formula: CS = (2 • Fm + 3 • Fs) Where: CS = composite score Fm = frequency of moderate hot flashes Fs = frequency of severe hot flashes The mean number of moderate and severe hot flashes recorded in the Run-In Period was used to calculate the baseline composite score.

Depression \& anxiety were measured using the Hospital Anxiety \& Depression Scale (HADS). The HADS is a scale developed to assess anxiety \& depression. The HADS Scale consists of 14 Questions (7 relating to anxiety; 7 relating to depression) with possible scores ranging from 0 to 21. The results presented below are the number of participants with abnormal HADS Scores for both Abnormal Anxiety \& Abnormal Depression combined at Week 8.

Mood was measured 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 "335." The percentage of participants who had a change from baseline in the total score at Week 4 is reported below.

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 compared to baseline. A responder is defined as a subject who had an improvement in the HFRDIS score. An improvement is define as a score ≤3 on each question.

The Clinical Global Impression Scale (CGIS) was completed by the investigator and was used to measure the severity of the VMS at any given time and the improvement from baseline. Responders were defined as subjects who achieved a score of 1 to 3 where 1 = very much improved, 2 = much improved, and 3 = minimally improved. Non-responders were defined as subjects who achieved a score of 4 to 7 where 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

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.

The Subject Impression Numerical Rating Scale (NRS) is an 11-point scale was used to measure how bothered a subject was by hot flashes both during the day and the night. The measure being reported below is percentage of responders who had an improvement in NRS score at Week 4 compared to baseline. A responder is defined as a subject who had an improvement in the NRS score. An improvement is define as a score ≤3 on each question.

Body Mass Index (BMI) was calculated by using height in centimeters and weight in kilograms.