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

Hot Flashes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00786188
• Other study ID #: N30-002
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2008
• Last updated: October 14, 2015
• Start date: November 2008
• Est. completion date: June 2009

Study information

• Verified date: October 2015
• Source: Noven Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 41 Years and older

Eligibility

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. History of hypersensitivity or adverse reaction to paroxetine mesylate

2. Use of an investigational study medication within 30 days prior to screening or during the study

3. Concurrent participation in another clinical trial or previous participation in this trial

4. Family of investigational-site staff

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hot Flashes

Intervention

Drug:
• Brisdelle (paroxetine mesylate)
Eligible subjects will be randomized to receive Brisdelle™ (paroxetine mesylate) Capsules 7.5 mg.
• Sugar pill
Subjects will receive a sugar pill.

Locations

Country	Name	City	State
United States	Chattanooga Medical Research, LLC	Chattanooga	Tennessee
United States	Hawthorne Research	Greensboro	North Carolina
United States	Altus Research	Lake Worth	Florida
United States	Anchor Research Center	Naples	Florida
United States	Philadelphia Clinical Research	Philadelphia	Pennsylvania
United States	National Clinical Research, Inc.	Richmond	Virginia
United States	Virginia Women's Center	Richmond	Virginia
United States	Women's Clinical Research Center	Seattle	Washington
United States	North Spokane Women's Clinic Research	Spokane	Washington
United States	Hawthorne Medical Research, Inc.	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Noven Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (4)

Fugate SE, Church CO. Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother. 2004 Sep;38(9):1482-99. Epub 2004 Aug 3. Review. — View Citation

Greene JG. A factor analytic study of climacteric symptoms. J Psychosom Res. 1976;20(5):425-30. — View Citation

Kritz-Silverstein D, Goldani Von Mühlen D, Barrett-Connor E. Prevalence and clustering of menopausal symptoms in older women by hysterectomy and oophorectomy status. J Womens Health Gend Based Med. 2000 Sep;9(7):747-55. — View Citation

Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, Nicolaidis C, Walker M, Humphrey L. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006 May 3;295(17):2057-71. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No