Title
Eight-Week Efficacy & Safety Study of Brisdelle™ (Formerly Known as Mesafem) in the Treatment of Vasomotor Symptoms Associated With Menopause
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
Phase
Phase 2Lead Sponsor
Noven TherapeuticsStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Hot FlashesIntervention/Treatment
paroxetine ...Study Participants
102This 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
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.
Eligible subjects will be randomized to receive Brisdelle™ (paroxetine mesylate) Capsules 7.5 mg.
Subjects will receive a sugar pill.
Eligible subjects will be randomized to receive a sugar pill.
Eligible subjects will be randomized to receive Brisdelle (paroxetine mesylate) Capsules 7.5 mg.
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
| Event Type | Organ System | Event Term | Brisdelle (Paroxetine Mesylate) Capsules 7.5 mg | Placebo - Sugar Pill |
|---|
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.
