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

Study Overview
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Brief Summary
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This is an exploratory 8-week, multicenter, double-blind, randomized, placebo-controlled study of Brisdelle (paroxetine mesylate) Capsules 7.5 mgin subjects with moderate to severe postmenopausal vasomotor symptoms (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

Detailed Description
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Eligible subjects will be entered into a 1-week observation period followed by a 1-week run-in period. Following completion of the run-in period, eligible subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo in a 1:1 ratio. Study drug will be administered once daily at bedtime. Symptom assessment questionnaires will be administered at baseline and at Day 28 and Day 57 visits.

Official Title
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A Phase 2, Exploratory, Eight-Week, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Efficacy and Safety Study of Mesafem (Paroxetine Mesylate) Capsules in the Treatment of Vasomotor Symptoms Associated With Menopause

Conditions
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Hot Flashes

Intervention / Treatment
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* Drug: Brisdelle (paroxetine mesylate)
* Drug: Sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, >40 years of age 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 Spontaneous amenorrhea for at least 12 consecutive months Amenorrhea for at least 6 months and meet the biochemical criteria for menopause Bilateral salpingo-oophorectomy >6 weeks with or without hysterectomy Exclusion Criteria: History of hypersensitivity or adverse reaction to paroxetine mesylate Use of an investigational study medication within 30 days prior to screening or during the study Concurrent participation in another clinical trial or previous participation in this trial Family of investigational-site staff

Ages Eligible for Study
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Minimum Age: 41 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brisdelle (paroxetine mesylate)<br>Eligible subjects will be randomized to receive Brisdelle (paroxetine mesylate) Capsules 7.5 mg. | Drug: Brisdelle (paroxetine mesylate)<br>* Eligible subjects will be randomized to receive Brisdelle™ (paroxetine mesylate) Capsules 7.5 mg.<br>* Other names: LDMP (Low-Dose Mesylate salt of Paroxetine);|
| Placebo Comparator: Placebo - Sugar Pill<br>Eligible subjects will be randomized to receive a sugar pill. | Drug: Sugar pill<br>* Subjects will receive a sugar pill.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 8 | 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. | Week 4 and Week 8 | 
| Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 8 | 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. | Week 4 and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Climacteric Symptoms at Week 8 | 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. | Week 8 | 
| Change From Baseline in Hot Flash Composite Score at Week 4 and Week 8 | 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. | Week 4 and Week 8 | 
| Effect of Brisdelle (Paroxetine Mesylate) Capsules on Depression and Anxiety at Week 8 | 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. | Week 8 | 
| Effect of Brisdelle (Paroxetine Mesylate) Capsules on Mood at Week 4 | 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. | Week 4 | 
| Effect of Brisdelle (Paroxetine Mesylate) Capsules on Improvement of Hot Flash Interference at Week 4 | 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. | Week 4 | 
| Proportion of Clinical Global Impression (CGI) Responders at Week 4 and Week 8 | 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. | Week 4 and Week 8 | 
| Asses the Effect of Brisdelle (Paroxetine Mesylate) Capsules on the Interference on Sexual Functioning at Week 8 | 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. | Week 8 | 
| Proportion of Numerical Rating Scale (NRS) True Responders at Week 4 and Week 8 | 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. | Week 4 and Week 8 | 
| Effect of Brisdelle (Paroxetine Mesylate) Capsules on BMI at Week 4 and Week 8 | Body Mass Index (BMI) was calculated by using height in centimeters and weight in kilograms. | Week 4 and Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menopause, Vasomotor Symptoms, Hot flash, Perimenopause, Nonhormonal therapies, Climacteric symptoms, Mesafem, Low-Dose Mesylate salt of Paroxetine (LDMP)