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

Hot Flashes Clinical Trial

Official title:

A Phase 3, Twenty-Four 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: NCT01101841
• Other study ID #: N30-004
• Status: Completed
• Phase: Phase 3
• First received: April 8, 2010
• Last updated: October 14, 2015
• Start date: March 2010
• Est. completion date: November 2011

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

To assess the safety and efficacy of Brisdelle (paroxetine mesylate) Capsules 7.5 mg for treatment of vasomotor symptoms (VMS) associated with menopause

Description:

The study is a 24-week, multicenter, double-blind, randomized, placebo-controlled study of Brisdelle (paroxetine mesylate) Capsules 7.5 mg in subjects with moderate to severe postmenopausal VMS, defined as follows:

1. Moderate VMS: Sensation of heat with sweating, able to continue activity

2. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 570
• Est. completion date: November 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 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. BMI = 40 kg/m²

2. Known non-responder to previous Selective serotonin reuptake inhibitor (SSRI) or Serotonin norepinephrine reuptake inhibitor (SNRI) treatment for VMS

3. History of self-injurious behavior

4. History of clinical diagnosis of depression; or treatment for depression

5. History of clinical diagnosis of borderline personality disorder

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

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

8. Family of investigational-site staff

Study Design

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

Related Conditions & MeSH terms

• Hot Flashes

Intervention

Drug:
• Brisdelle (paroxetine mesylate)
Eligible subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo capsules in a 1:1 ratio.
• Placebo capsules
Eligible subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo capsules in a 1:1 ratio.

Locations

Country	Name	City	State
United States	Visions Clinical Research	Boynton Beach	Florida
United States	Meridien Research	Brooksville	Florida
United States	East Valley Family Physicians PLC	Chandler	Arizona
United States	Chattanooga Medical Research, LLC	Chattanooga	Tennessee
United States	Women's Medical Research Group, LLC	Clearwater	Florida
United States	SC Clinical Research Center, LLC	Columbia	South Carolina
United States	Columbus Center for Women's Health Research	Columbus	Ohio
United States	Soapstone Center for Clinical Research	Decatur	Georgia
United States	Downtown Women's Health Care	Denver	Colorado
United States	Hawthorne Research	Greensboro	North Carolina
United States	The Woman's Hospital of Texas Clinical Research Center	Houston	Texas
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	Altus Research	Lake Worth	Florida
United States	Women's Clinic of Lincoln, PC	Lincoln	Nebraska
United States	Montgomery Women's Health Associates, PC	Montgomery	Alabama
United States	Phoenix Ob-Gyn Associates, LLC	Moorestown	New Jersey
United States	Coastal Carolina Research Center	Mt. Pleasant	South Carolina
United States	Anchor Research Center	Naples	Florida
United States	Clinical Research Associates, Inc.	Nashville	Tennessee
United States	Philadelphia Clinical Research	Philadelphia	Pennsylvania
United States	Clinical Trials Research Services, LLC	Pittsburgh	Pennsylvania
United States	National Clinical Research, Inc.	Richmond	Virginia
United States	Virginia Women's Center	Richmond	Virginia
United States	Rochester Clinical Research	Rochester	New York
United States	Genesis Center For Clinical Research	San Diego	California
United States	Mount Vernon Clinical Research, LLC	Sandy Springs	Georgia
United States	Apex Research Institute	Santa Ana	California
United States	Women's Clinical Research Center	Seattle	Washington
United States	North Spokane Women's Clinic Research	Spokane	Washington
United States	Chase Medical Research, LLC	Waterbury	Connecticut
United States	Comprehensive Clinical Trials, LLC	West Palm Beach	Florida
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 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	Week 4 and Week 12	No
Primary	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	Week 4 and Week 12	No
Secondary	Percent Persistence of Benefit, Statistically Significant Difference in Having 50% or More Reduction Compared to Baseline at Week 24.	Persistence of treatment benefit to 24 weeks post treatment was assessed by using the following responder analysis. Responders were defined as those subjects who achieved = 50% reduction from baseline in moderate to severe hot-flash frequency at Week 24; the percent change in hot flash frequency is calculated using the formula: Percent reduction at week 24 = [(number of moderate to severe hot flash frequency at baseline - number of moderate to severe hot flash frequency at week 24) / number of moderate to severe hot flash frequency at baseline ]*100%.	Week 24	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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).; Responders: Subjects with NRS Score of 5 Or Less. Non-Responders: Subjects With NRS Score of Greater than Or Equal to 6.	Week 4 and Week 12	No
Secondary	Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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".	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No
Secondary	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.	Week 4 and Week 12	No

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