N30-003: Efficacy/Safety Study of Brisdelle™ (Formerly Known as Mesafem) in the Treatment of Vasomotor Symptoms (VMS)

• Sponsor: Noven Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01361308
• Collaborator: (none)
• Enrollment: 614
• Locations: 74
• Arms: 2
• Duration (Months): 9.1
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety & efficacy of Brisdelle (paroxetine mesylate) Capsules 7.5 mg for treatment of vasomotor symptoms (VMS) associated with menopause.

Condition or Disease	Intervention/Treatment	Phase
Postmenopausal Symptoms	Drug: Brisdelle (paroxetine mesylate); Drug: Placebo capsules	Phase 3

Detailed Description

This is 12-week, multicenter, double-blind, randomized, placebo-controlled study of Brisdelle (paroxetine mesylate) Capsules 7.5 mg and placebo capsules in subjects with moderate to severe postmenopausal 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

The study is comprised of a screening period, a run-in period, a baseline visit, and a double-blind treatment period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 614 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Twelve-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
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brisdelle (paroxetine mesylate) Brisdelle (paroxetine mesylate)	Drug: Brisdelle (paroxetine mesylate); Subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84; Other Names: Former Names: Mesafem Capsules or LDMP (Low-Dose Mesylate salt of Paroxetine)
Placebo Comparator: Placebo Capsules Placebo Capsules	Drug: Placebo capsules; Subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Mean Change in Frequency of Moderate to Severe VMS From Baseline at Week 4 and Week 12. [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.

2. Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12 [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.

Secondary Outcome Measures

1. Clinical Meaningfulness Anchored to Patient Global Improvement (PGI-I) (%) [Week 4 and Week 12]

   A patient improvement scale questionnaire was used during participant visits. The clinical meaningfulness of the observed treatment effect was demonstrated by performing the following analysis: Subjects were categorized in to 2 groups (satisfied and unsatisfied). Based on a 7 point patient global impression (PGI) questionnaire which assesses the subject improvement in VMS. Subjects were considered satisfied with their treatment if their response to the question "Compared to before starting the study medication, how would you describe your hot flushes now?" is 'Very much better' (1) or 'Much better' (2) or 'A little better' (3) and will be considered unsatisfied if their response to the same question is 'No change' (4) or 'A little worse' (5) or 'Much worse' (6) or 'Very much worse' (7). Receiver Operator Curve (ROC) analysis was performed on the combined data. Subjects who were satisfied with their treatment were considered to have a treatment effect with clinical meaningfulness

2. Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median [Week 4 and Week 12]

   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.

3. Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median [Week 4 and Week 12]

   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.

4. Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median [Week 4 and Week 12]

   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.

5. Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median [Week 4 and Week 12]

   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.

6. Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median [Week 4 and Week 12]

   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.

7. Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median [Week 4 and Week 12]

   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.

8. Percentage of Responders [Week 4 and Week 12]

   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.

9. Percentage of Patient Global Improvement (PGI) Scale Responders (%) [Week 4 and Week 12]

   Percentage of PGI Responders: Subject's overall improvement in VMS from baseline assessed using the Patient Global Improvement (PGI) scale. Responders: Subjects Achieving a Score of "Very Much Better" Or "Much Better" Or "A Little Better". Non Responders: Subjects with a Score of "No Change" Or "A Little Worse" Or "Much Worse" Or "Very Much Worse". Patient Global Improvement (PGI) scale is described below: Compared to before starting study medication, how would you describe your hot flushes now? 0 = Not assessed = Very much better = Much better = A little better = No change = A little worse = Much worse = Very much worse

10. Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS) [Week 4 and Week 12]

    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). The measure being reported below is percentage of responders who had an improvement in NRSscore at Week 4 and Week 12 compared to baseline. A responder is defined as a subject who had an improvement in the NRS score. An improvement is defined as a score ≤5 on each question.

11. Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score [Week 4 and Week 12]

    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. The results presented below are change from baseline at Week 4 and Week 12.

12. 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) [Week 4 and Week 12]

    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.

13. Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale. [Week 4 and Week 12]

    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".

14. Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression [Week 4 and Week 12]

    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.

15. Assessment of Mood [Week 4 and Week 12]

    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.

16. BMI Change From Baseline (kg/m2), Median [Week 4 and Week 12]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female, ≥ 40 years of age at screening (inclusive)

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 to the screening visit

3. Spontaneous amenorrhea for at least 12 consecutive months or

4. Amenorrhea for at least 6 months and meet the biochemical criteria for menopause or

5. Bilateral salpingo-oophorectomy ≥ 6 weeks with or without hysterectomy

Exclusion Criteria:

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

2. History of self injurious behavior

3. History of clinical diagnosis of depression or treatment for depression

4. History of clinical diagnosis of borderline personality disorder

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

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

7. Family of investigational-site staff

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wilmax Clinical Research	Mobile	Alabama	United States	36608
2	East Valley Family Physicians PLC	Chandler	Arizona	United States	85224
3	Advanced Research Associates	Glendale	Arizona	United States	85308
4	Premier Research Group Limited	Peoria	Arizona	United States	85381
5	Verona Clinical Research, Inc	Tucson	Arizona	United States	85710
6	NEA Baptist Women's Clinic	Jonesboro	Arkansas	United States	72401
7	Grossmont Center for Clinical Research	La Mesa	California	United States	91942
8	High Desert Medical Group	Lancaster	California	United States	93534
9	Facey Medical Foundation	Mission Hills	California	United States	91345
10	Northern California Research	Sacramento	California	United States	95821
11	University Clinical Research	San Diego	California	United States	92103
12	Medical Center for Clinical Research	San Diego	California	United States	92108
13	Apex Research Institute	Santa Ana	California	United States	92705
14	Downtown Women's Health Care	Denver	Colorado	United States	80218
15	Horizons Clinical Research Center, LLC	Denver	Colorado	United States	80220
16	The Women's Clinic of Northern Colorado	Fort Collins	Colorado	United States	80524
17	Danbury Clinical Research, LLC	Danbury	Connecticut	United States	06810
18	Coastal Connecticut Research, LLC	New London	Connecticut	United States	06320
19	James A. Simon, MD, PC	Washington	District of Columbia	United States	20036
20	Meridien Research	Bradenton	Florida	United States	34208
21	Meridien Research	Brooksville	Florida	United States	34601
22	Tampa Bay Medical Research, Inc.	Clearwater	Florida	United States	33761
23	DBC Research	Deerfield Beach	Florida	United States	33441
24	Clinical Physiology Associates	Fort Myers	Florida	United States	33916
25	University of Florida College of Medicine - Jacksonville Southside Women's Health	Jacksonville	Florida	United States	32207
26	Health Awareness, Inc.	Jupiter	Florida	United States	33458
27	Suncoast Clinical Research, Inc.	New Port Richey	Florida	United States	34652
28	Suncoast Clinical Research, Inc.	Palm Harbor	Florida	United States	34684
29	Soapstone Center for Clinical Research	Decatur	Georgia	United States	30034
30	Mount Vernon Clinical Research, LLC	Sandy Springs	Georgia	United States	30328
31	Advanced Clinical Research	Boise	Idaho	United States	83642
32	Affinity Healthcare	Arlington Heights	Illinois	United States	60004
33	Bluegrass Clinical Research, Inc.	Louisville	Kentucky	United States	40291
34	Beacon Clinical Research, LLC	Brockton	Massachusetts	United States	02301
35	Neurocare Center for Research	Newton	Massachusetts	United States	02459
36	ClinSite, LLC	Ann Arbor	Michigan	United States	48106
37	Professional Clinical Research	Benzonia	Michigan	United States	49616
38	Hutzel Womens Health Research	Detroit	Michigan	United States	48201
39	Professional Clinical Research	Interlochen	Michigan	United States	49643
40	Women's Clinic of Lincoln, PC	Lincoln	Nebraska	United States	68510
41	Clinical Research Center of Nevada	Las Vegas	Nevada	United States	89104
42	Lawrence Ob-Gyn Assoc., PC	Lawrenceville	New Jersey	United States	08648
43	Albuquerque Clinical Trials	Albuquerque	New Mexico	United States	87102
44	New Mexico Clinical Research & Osteoporosis Center, Inc.	Albuquerque	New Mexico	United States	87106
45	NY Center for Women's Health Research	New York	New York	United States	10038
46	Wake Research Associates	Raleigh	North Carolina	United States	27612
47	Clinical Trials of America, Inc.	Winston-Salem	North Carolina	United States	27103
48	Hawthorne Medical Research, Inc.	Winston-Salem	North Carolina	United States	27103
49	Rapid Medical Research, Inc.	Cleveland	Ohio	United States	44122
50	Columbus Center for Women's Health Research	Columbus	Ohio	United States	43213
51	Complete Healthcare for Women	Columbus	Ohio	United States	43231
52	HWC Women's Research Center	Englewood	Ohio	United States	45424
53	University Hospitals of Cleveland Landerbrook Health Center	Mayfield Heights	Ohio	United States	44124
54	Sooner Clinical Research, Inc.	Oklahoma City	Oklahoma	United States	73112
55	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
56	Philadelphia Clinical Research	Philadelphia	Pennsylvania	United States	19114
57	Clinical Trials Research Services, LLC	Pittsburgh	Pennsylvania	United States	15206
58	Susan L Floyd, MD, PC	Wexford	Pennsylvania	United States	15090
59	Partners in Clinical Research	Cumberland	Rhode Island	United States	02864
60	Coastal Carolina Research Center	Mt. Pleasant	South Carolina	United States	29464
61	Chattanooga Medical Research, LLC	Chattanooga	Tennessee	United States	37404
62	Access Clinical Trials, Inc.	Nashville	Tennessee	United States	37043
63	Tekton Research	Austin	Texas	United States	78745
64	DiscoveResearch, Inc.	Bryan	Texas	United States	77802
65	Advances In Health, Inc.	Houston	Texas	United States	77030
66	The Woman's Hospital of Texas Clinical Research Center	Houston	Texas	United States	77054
67	Research Across America	Katy	Texas	United States	77450
68	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
69	Radiant Research, Inc.	San Antonio	Texas	United States	78229
70	Virginia Women's Center	Richmond	Virginia	United States	23233
71	National Clinical Research, Inc.	Richmond	Virginia	United States	23294
72	Tidewater Clinical Research, Inc	Virginia Beach	Virginia	United States	23456
73	Women's Clinical Research Center	Seattle	Washington	United States	98105
74	North Spokane Women's Clinic Research	Spokane	Washington	United States	99207

Sponsors and Collaborators

• Noven Therapeutics

Investigators

• Principal Investigator: Corey Jacobs, MD,
• Principal Investigator: Donna DeSantis, MD,
• Principal Investigator: Robert Phillips, MD,
• Principal Investigator: Louise Taber, MD,
• Principal Investigator: Paige C. Brainard, MD,
• Principal Investigator: Mark Stripling, MD,
• Principal Investigator: Gioi Smith-Nguyen, MD,
• Principal Investigator: Anthony Dulgeroff, MD,
• Principal Investigator: Elise Kwon, MD,
• Principal Investigator: Douglas Young, MD,
• Principal Investigator: William Koltun, MD,
• Principal Investigator: Dana Shipp, MD,
• Principal Investigator: Eric Ross, MD,
• Principal Investigator: Arthur Waldbaum, MD,
• Principal Investigator: Theodore Cooper, MD,
• Principal Investigator: J B. Stern, MD,
• Principal Investigator: Paul DiGrazia, MD,
• Principal Investigator: Robert Spitz, MD,
• Principal Investigator: James A Simon, MD,
• Principal Investigator: Mildred Farmer, MD,
• Principal Investigator: James Andersen, MD,
• Principal Investigator: Steven Bowman, MD,
• Principal Investigator: Rene Casanova, MD,
• Principal Investigator: Mary Yankaskas, MD,
• Principal Investigator: Andrew Kaunitz, MD,
• Principal Investigator: Ronald Surowitz, MD,
• Principal Investigator: Lisa Cohen, MD,
• Principal Investigator: Lisa Vendeland, MD,
• Principal Investigator: Tyrone Malloy, MD,
• Principal Investigator: Stephen C. Blank, MD,
• Principal Investigator: Mark Turner, MD,
• Principal Investigator: Carl R Lang, MD,
• Principal Investigator: Arthur Donovan, MD,
• Principal Investigator: Armen Arslanian, MD,
• Principal Investigator: Shiao-Yu Lee, MD,
• Principal Investigator: Gayle Moyer, MD,
• Principal Investigator: Geoffrey Turner, MD,
• Principal Investigator: Susan L Hendrix, MD,
• Principal Investigator: Mark Barber, MD,
• Principal Investigator: Stephen Swanson, MD,
• Principal Investigator: Timothy Sauter, MD,
• Principal Investigator: Steven Sussman, MD,
• Principal Investigator: Elizabeth Bretton, MD,
• Principal Investigator: Lance A. Rudolph, MD,
• Principal Investigator: Kenneth Levey, MD,
• Principal Investigator: Pouru Bhiwandi, MD,
• Principal Investigator: Richard E. Hedrick, MD,
• Principal Investigator: Gregory P Tarleton, MD,
• Principal Investigator: Mira Baron, MD,
• Principal Investigator: David J Portman, MD,
• Principal Investigator: Milroy Samuel, MD,
• Principal Investigator: Stuart Weprin, MD,
• Principal Investigator: James Liu, MD,
• Principal Investigator: Angelique Barreto, MD,
• Principal Investigator: Marvin Kalafer, MD,
• Principal Investigator: Larry S. Seidman, MD,
• Principal Investigator: Saul R. Berg, MD,
• Principal Investigator: Susan Floyd, MD,
• Principal Investigator: Scott Wilson, MD,
• Principal Investigator: Cynthia Strout, MD,
• Principal Investigator: D. S. Harnsberger, MD,
• Principal Investigator: Janet Dittus, MD,
• Principal Investigator: Gregg Lucksinger, MD,
• Principal Investigator: Anna Damian, MD,
• Principal Investigator: Sandra Hurtado, MD,
• Principal Investigator: Alfred Poindexter, MD,
• Principal Investigator: Nancy Campbell, MD,
• Principal Investigator: William Jennings, MD,
• Principal Investigator: Jose Ruiz, MD,
• Principal Investigator: John A. Hoekstra, MD,
• Principal Investigator: Peter A. Zedler, MD,
• Principal Investigator: Franklin Morgan, MD,
• Principal Investigator: Robin Kroll, MD,
• Principal Investigator: Derrick R Havin, MD,

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Sponsor

Publications

None provided.

• Responsible Party: Noven Therapeutics
• ClinicalTrials.gov Identifier: NCT01361308
• Other Study ID Numbers: N30-003
• First Posted: May 26, 2011
• Last Update Posted: Oct 15, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Noven Therapeutics: Menopause; Vasomotor Symptoms; Hot Flashes Perimenopause; Climacteric Symptoms; Mesafem; Low-Dose Mesylate salt of Paroxetine (LDMP)
• Additional relevant MeSH terms: Paroxetine

Study Results

Participant Flow

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Period Title: Overall Study
STARTED	306	308
COMPLETED	271	278
NOT COMPLETED	35	30

Baseline Characteristics

Arm/Group Title	Brisdelle (Paroxetine Mesylate) Capsules	Placebo Capsules	Total
Arm/Group Description	Subjects were randomized to receive either Brisdelle (paroxetine mesylate) Capsules or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive either Brisdelle (paroxetine mesylate) Capsules or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84	Total of all reporting groups
Overall Participants	306	308	614
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	281 91.8%	284 92.2%	565 92%
>=65 years	25 8.2%	24 7.8%	49 8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.9 (5.95)	54.5 (6.27)	54.7 (6.11)
Sex: Female, Male (Count of Participants)
Female	306 100%	308 100%	614 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	306 100%	308 100%	614 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Frequency of Moderate to Severe VMS From Baseline at Week 4 and Week 12.
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	301	305
Baseline	11.79 (4.87)	11.65 (4.39)
Week 4	-4.71 (4.00)	-3.36 (4.65)
Week 12	-6.22 (4.53)	-5.33 (5.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules, Placebo Capsules
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Week 4 frequency
	Method	Rank transformed ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules, Placebo Capsules
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0090
	Comments	Week 12 frequency
	Method	Rank transformed ANCOVA
	Comments

2. Secondary Outcome

Title	Clinical Meaningfulness Anchored to Patient Global Improvement (PGI-I) (%)
Description	A patient improvement scale questionnaire was used during participant visits. The clinical meaningfulness of the observed treatment effect was demonstrated by performing the following analysis: Subjects were categorized in to 2 groups (satisfied and unsatisfied). Based on a 7 point patient global impression (PGI) questionnaire which assesses the subject improvement in VMS. Subjects were considered satisfied with their treatment if their response to the question "Compared to before starting the study medication, how would you describe your hot flushes now?" is 'Very much better' (1) or 'Much better' (2) or 'A little better' (3) and will be considered unsatisfied if their response to the same question is 'No change' (4) or 'A little worse' (5) or 'Much worse' (6) or 'Very much worse' (7). Receiver Operator Curve (ROC) analysis was performed on the combined data. Subjects who were satisfied with their treatment were considered to have a treatment effect with clinical meaningfulness
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	301	305
Week 4	50 16.3%	37 12%
Week 12	51 16.7%	43 14%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules, Placebo Capsules
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Clinical meaningfulness at week 4
	Method	Logit model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules, Placebo Capsules
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments	Clinical meaningfulness at week 12
	Method	Logit model
	Comments

3. Secondary Outcome

Title	Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	289	288
Week 4	-8.33	-7.12
Week 12	-12.00	-11.05

4. Secondary Outcome

Title	Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	211	206
Week 4	-31.00	-23.50
Week 12	-46.00	-35.00

5. Secondary Outcome

Title	Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	77	87
Week 4	-28.00	-19.00
Week 12	-35.00	-37.50

6. Secondary Outcome

Title	Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	206	203
Week 4	-0.055	0.00
Week 12	-0.043	-0.010

7. Secondary Outcome

Title	Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	74	86
Week 4	-0.023	-0.014
Week 12	-0.079	-0.030

8. Secondary Outcome

Title	Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	280	282
Week 4	-3.00	-2.00
Week 12	-4.00	-3.00

9. Secondary Outcome

Title	Percentage of Responders
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	301	305
Week 4	40.20 13.1%	29.18 9.5%
Week 12	49.83 16.3%	44.92 14.6%

10. Secondary Outcome

Title	Percentage of Patient Global Improvement (PGI) Scale Responders (%)
Description	Percentage of PGI Responders: Subject's overall improvement in VMS from baseline assessed using the Patient Global Improvement (PGI) scale. Responders: Subjects Achieving a Score of "Very Much Better" Or "Much Better" Or "A Little Better". Non Responders: Subjects with a Score of "No Change" Or "A Little Worse" Or "Much Worse" Or "Very Much Worse". Patient Global Improvement (PGI) scale is described below: Compared to before starting study medication, how would you describe your hot flushes now? 0 = Not assessed = Very much better = Much better = A little better = No change = A little worse = Much worse = Very much worse
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	301	305
Week 4	68.21 22.3%	61.75 20%
Week 12	72.82 23.8%	64.60 21%

11. Secondary Outcome

Title	Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS)
Description	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). The measure being reported below is percentage of responders who had an improvement in NRSscore at Week 4 and Week 12 compared to baseline. A responder is defined as a subject who had an improvement in the NRS score. An improvement is defined as a score ≤5 on each question.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	300	302
Week 4	39.00 12.7%	30.46 9.9%
Week 12	46.51 15.2%	45.72 14.8%

12. Secondary Outcome

Title	Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score
Description	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. The results presented below are change from baseline at Week 4 and Week 12.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	280	282
Week 4	-0.34 (3.28)	-0.43 (2.87)
Week 12	-0.36 (3.77)	-0.61 (3.30)

13. Secondary Outcome

Title	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)
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	278	275
Week 4	26.98 8.8%	32.00 10.4%
Week 12	19.67 6.4%	21.95 7.1%

14. Secondary Outcome

Title	Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale.
Description	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".
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	280	285
Week 4	68.93 22.5%	57.89 18.8%
Week 12	71.88 23.5%	63.92 20.8%

15. Secondary Outcome

Title	Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	281	281
Week 4	3.56 1.2%	3.56 1.2%
Week 12	2.02 0.7%	2.75 0.9%

16. Secondary Outcome

Title	Assessment of Mood
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	280	280
Week 4	39.29 12.8%	35.36 11.5%
Week 12	43.90 14.3%	34.25 11.1%

17. Secondary Outcome

Title	BMI Change From Baseline (kg/m2), Median
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	282	288
Week 4	0.00	0.04
Week 12	0.00	0.17

18. Primary Outcome

Title	Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12
Description	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.
Time Frame	Week 4 and Week 12

Outcome Measure Data

Analysis Population Description

The outcome data presented for these measurements were obtained using a scale questionnaire. Data were analyzed only from participants who completed and turned in the completed questionnaire. Therefore, the number of participants analyzed is not consistent with numbers provided in any of the rows in the participant flow module.

Arm/Group Title	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules	Placebo Capsules
Arm/Group Description	Subjects were randomized to receive Brisdelle (paroxetine mesylate) 7.5 mg Capsules administered orally once daily at bedtime beginning on Day 1 and continuing up to Day 84	Subjects were randomized to receive placebo capsules (sugar pill) orally administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
Measure Participants	301	305
Baseline	2.528 (0.30)	2.526 (0.31)
Week 4	-0.091 (0.25)	-0.046 (0.23)
Week 12	-0.104 (0.29)	-0.084 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules, Placebo Capsules
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments	Week 4 severity
	Method	Rank transformed ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Brisdelle (Paroxetine Mesylate) 7.5 mg Capsules, Placebo Capsules
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1658
	Comments	Week 12 severity
	Method	Rank transformed ANCOVA
	Comments

Adverse Events

Time Frame	12 Weeks
Arm/Group Title	Brisdelle (Paroxetine Mesylate) Capsules		Placebo Capsules
Arm/Group Description	Subjects were randomized to receive either Brisdelle (paroxetine mesylate) Capsules or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84		Subjects were randomized to receive either Brisdelle (paroxetine mesylate) Capsules or placebo in a 1:1 ratio, administered once daily at bedtime beginning on Day 1 and continuing up to Day 84
All Cause Mortality
	Brisdelle (Paroxetine Mesylate) Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Brisdelle (Paroxetine Mesylate) Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/301 (0.7%)		1/305 (0.3%)
Cardiac disorders
Cardio-respiratory arrest	1/301 (0.3%)	1	0/305 (0%)	0
Arteriosclerosis coronary artery	1/301 (0.3%)	1	0/305 (0%)	0
Injury, poisoning and procedural complications
Upper limb fracture	0/301 (0%)	0	1/305 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Brisdelle (Paroxetine Mesylate) Capsules		Placebo Capsules
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/301 (44.5%)		129/305 (42.3%)
Blood and lymphatic system disorders
Lymphadenitis	0/301 (0%)	0	1/305 (0.3%)	1
Lymphadenopathy	0/301 (0%)	0	1/305 (0.3%)	1
Lymphocytosis	1/301 (0.3%)	1	0/305 (0%)	0
Cardiac disorders
Arrhythmia supraventricular	0/301 (0%)	0	1/305 (0.3%)	1
Arteriosclerosis coronary artery	1/301 (0.3%)	1	0/305 (0%)	0
Cardio-respiratory arrest	1/301 (0.3%)	1	0/305 (0%)	0
Palpitations	3/301 (1%)	3	1/305 (0.3%)	1
Ear and labyrinth disorders
Deafness	1/301 (0.3%)	1	0/305 (0%)	0
Ear pain	1/301 (0.3%)	1	1/305 (0.3%)	1
Tinnitus	0/301 (0%)	0	1/305 (0.3%)	1
Vertigo	0/301 (0%)	0	1/305 (0.3%)	1
Endocrine disorders
Goitre	1/301 (0.3%)	1	0/305 (0%)	0
Eye disorders
Dry eye	1/301 (0.3%)	1	1/305 (0.3%)	1
Lacrimation increased	0/301 (0%)	0	1/305 (0.3%)	1
Vision blurred	2/301 (0.7%)	2	1/305 (0.3%)	1
Vitreous detachment	0/301 (0%)	0	1/305 (0.3%)	1
Gastrointestinal disorders
Abdominal distension	1/301 (0.3%)	1	1/305 (0.3%)	1
Abdominal pain	1/301 (0.3%)	1	2/305 (0.7%)	2
Abdominal pain lower	0/301 (0%)	0	1/305 (0.3%)	1
Abdominal pain upper	0/301 (0%)	0	2/305 (0.7%)	2
Breath odour	0/301 (0%)	0	1/305 (0.3%)	1
Constipation	3/301 (1%)	3	3/305 (1%)	3
Dental caries	1/301 (0.3%)	1	1/305 (0.3%)	1
Dental discomfort	0/301 (0%)	0	1/305 (0.3%)	1
Diarrhoea	11/301 (3.7%)	13	6/305 (2%)	6
Dry mouth	3/301 (1%)	3	3/305 (1%)	3
Dyspepsia	0/301 (0%)	0	1/305 (0.3%)	1
Dysphagia	1/301 (0.3%)	1	0/305 (0%)	0
Flatulence	0/301 (0%)	0	2/305 (0.7%)	2
Food poisoning	0/301 (0%)	0	1/305 (0.3%)	1
Gastrooesophageal reflux disease	1/301 (0.3%)	1	2/305 (0.7%)	2
Haemorrhoids	1/301 (0.3%)	1	1/305 (0.3%)	1
Nausea	9/301 (3%)	9	5/305 (1.6%)	5
Oral pain	0/301 (0%)	0	1/305 (0.3%)	1
Rectal haemorrhage	1/301 (0.3%)	1	0/305 (0%)	0
Retching	1/301 (0.3%)	1	0/305 (0%)	0
Toothache	1/301 (0.3%)	1	0/305 (0%)	0
Vomiting	4/301 (1.3%)	4	3/305 (1%)	3
General disorders
Bloody discharge	0/301 (0%)	0	1/305 (0.3%)	2
Chest pain	1/301 (0.3%)	1	0/305 (0%)	0
Chills	1/301 (0.3%)	1	0/305 (0%)	0
Energy increased	1/301 (0.3%)	1	0/305 (0%)	0
Fatigue	8/301 (2.7%)	8	2/305 (0.7%)	2
Influenza like illness	1/301 (0.3%)	2	0/305 (0%)	0
Irritability	2/301 (0.7%)	2	4/305 (1.3%)	4
Malaise	1/301 (0.3%)	1	0/305 (0%)	0
Oedema peripheral	1/301 (0.3%)	1	0/305 (0%)	0
Pain	0/301 (0%)	0	1/305 (0.3%)	1
Pyrexia	1/301 (0.3%)	1	3/305 (1%)	3
Thirst	1/301 (0.3%)	1	0/305 (0%)	0
Hepatobiliary disorders
Gallbladder disorder	0/301 (0%)	0	1/305 (0.3%)	1
Immune system disorders
Seasonal allergy	1/301 (0.3%)	1	1/305 (0.3%)	1
Infections and infestations
Bronchitis	3/301 (1%)	3	2/305 (0.7%)	2
Cystitis	1/301 (0.3%)	1	0/305 (0%)	0
Diverticulitis	0/301 (0%)	0	2/305 (0.7%)	2
Ear infection	0/301 (0%)	0	1/305 (0.3%)	1
Ear lobe infection	0/301 (0%)	0	1/305 (0.3%)	1
Fungal infection	0/301 (0%)	0	3/305 (1%)	3
Gastroenteritis	0/301 (0%)	0	1/305 (0.3%)	1
Gastroenteritis viral	1/301 (0.3%)	1	1/305 (0.3%)	1
Gastrointestinal viral infection	1/301 (0.3%)	1	0/305 (0%)	0
Herpes virus infection	1/301 (0.3%)	1	0/305 (0%)	0
Herpes zoster	1/301 (0.3%)	1	1/305 (0.3%)	1
Influenza	0/301 (0%)	0	1/305 (0.3%)	1
Nasopharyngitis	10/301 (3.3%)	10	9/305 (3%)	9
Oral herpes	1/301 (0.3%)	1	0/305 (0%)	0
Pharyngitis	1/301 (0.3%)	1	0/305 (0%)	0
Pneumonia	1/301 (0.3%)	1	1/305 (0.3%)	1
Sinusitis	4/301 (1.3%)	4	11/305 (3.6%)	11
Subcutaneous abscess	1/301 (0.3%)	1	0/305 (0%)	0
Tooth infection	1/301 (0.3%)	1	0/305 (0%)	0
Upper respiratory tract infection	4/301 (1.3%)	4	8/305 (2.6%)	8
Urinary tract infection	6/301 (2%)	6	5/305 (1.6%)	5
Vaginal infection	0/301 (0%)	0	1/305 (0.3%)	1
Viral rash	0/301 (0%)	0	1/305 (0.3%)	1
Vulvovaginal mycotic infection	2/301 (0.7%)	2	1/305 (0.3%)	1
Injury, poisoning and procedural complications
Cartilage injury	0/301 (0%)	0	1/305 (0.3%)	1
Concussion	1/301 (0.3%)	1	0/305 (0%)	0
Contusion	1/301 (0.3%)	1	3/305 (1%)	4
Excoriation	0/301 (0%)	0	1/305 (0.3%)	1
Eye injury	0/301 (0%)	0	1/305 (0.3%)	1
Joint sprain	1/301 (0.3%)	1	2/305 (0.7%)	2
Limb injury	1/301 (0.3%)	1	0/305 (0%)	0
Muscle injury	1/301 (0.3%)	1	1/305 (0.3%)	1
Muscle strain	0/301 (0%)	0	3/305 (1%)	3
Procedural pain	1/301 (0.3%)	1	0/305 (0%)	0
Skin laceration	1/301 (0.3%)	1	0/305 (0%)	0
Thermal burn	1/301 (0.3%)	1	1/305 (0.3%)	1
Upper limb fracture	0/301 (0%)	0	1/305 (0.3%)	1
Investigations
Alanine aminotransferase increased	0/301 (0%)	0	1/305 (0.3%)	1
Blood calcium increased	0/301 (0%)	0	1/305 (0.3%)	1
Blood glucose increased	1/301 (0.3%)	1	0/305 (0%)	0
Blood phosphorus increased	0/301 (0%)	0	1/305 (0.3%)	1
Blood pressure increased	1/301 (0.3%)	1	2/305 (0.7%)	2
Carotid bruit	0/301 (0%)	0	1/305 (0.3%)	1
Electrocardiogram abnormal	2/301 (0.7%)	2	0/305 (0%)	0
Haematocrit increased	1/301 (0.3%)	1	0/305 (0%)	0
Haemoglobin increased	1/301 (0.3%)	1	0/305 (0%)	0
Heart rate increased	1/301 (0.3%)	1	0/305 (0%)	0
Liver function test abnormal	2/301 (0.7%)	2	0/305 (0%)	0
Transaminases increased	1/301 (0.3%)	1	0/305 (0%)	0
Urine output decreased	0/301 (0%)	0	1/305 (0.3%)	1
Weight increased	1/301 (0.3%)	1	2/305 (0.7%)	2
Metabolism and nutrition disorders
Decreased appetite	1/301 (0.3%)	1	1/305 (0.3%)	1
Fluid retention	1/301 (0.3%)	1	1/305 (0.3%)	1
Food craving	1/301 (0.3%)	1	0/305 (0%)	0
Vitamin D deficiency	0/301 (0%)	0	1/305 (0.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	3/301 (1%)	3	6/305 (2%)	6
Arthritis	1/301 (0.3%)	1	0/305 (0%)	0
Back pain	4/301 (1.3%)	4	4/305 (1.3%)	5
Bursitis	1/301 (0.3%)	1	1/305 (0.3%)	1
Costochondritis	1/301 (0.3%)	1	0/305 (0%)	0
Flank pain	0/301 (0%)	0	1/305 (0.3%)	1
Intervertebral disc protrusion	0/301 (0%)	0	1/305 (0.3%)	1
Monarthritis	1/301 (0.3%)	1	0/305 (0%)	0
Muscle spasms	0/301 (0%)	0	4/305 (1.3%)	4
Muscle tightness	2/301 (0.7%)	2	0/305 (0%)	0
Musculoskeletal chest pain	1/301 (0.3%)	1	1/305 (0.3%)	1
Musculoskeletal stiffness	2/301 (0.7%)	2	0/305 (0%)	0
Myalgia	3/301 (1%)	4	1/305 (0.3%)	1
Osteoarthritis	0/301 (0%)	0	1/305 (0.3%)	1
Osteopenia	0/301 (0%)	0	1/305 (0.3%)	1
Osteoporosis	1/301 (0.3%)	1	0/305 (0%)	0
Pain in extremity	1/301 (0.3%)	1	2/305 (0.7%)	2
Temporomandibular joint syndrome	0/301 (0%)	0	1/305 (0.3%)	1
Tendonitis	1/301 (0.3%)	1	0/305 (0%)	0
Nervous system disorders
Crying	0/301 (0%)	0	1/305 (0.3%)	2
Disturbance in attention	0/301 (0%)	0	1/305 (0.3%)	1
Dizziness	8/301 (2.7%)	8	2/305 (0.7%)	2
Dysgeusia	1/301 (0.3%)	1	0/305 (0%)	0
Headache	13/301 (4.3%)	13	14/305 (4.6%)	17
Hypersomnia	2/301 (0.7%)	2	0/305 (0%)	0
Hypoaesthesia	1/301 (0.3%)	1	1/305 (0.3%)	1
Lethargy	2/301 (0.7%)	2	3/305 (1%)	3
Memory impairment	1/301 (0.3%)	1	0/305 (0%)	0
Migraine	1/301 (0.3%)	1	1/305 (0.3%)	1
Paraesthesia	0/301 (0%)	0	1/305 (0.3%)	1
Restless legs syndrome	3/301 (1%)	3	0/305 (0%)	0
Sedation	2/301 (0.7%)	2	0/305 (0%)	0
Sinus headache	1/301 (0.3%)	1	0/305 (0%)	0
Somnolence	3/301 (1%)	3	1/305 (0.3%)	1
Tremor	1/301 (0.3%)	1	0/305 (0%)	0
Psychiatric disorders
Abnormal dreams	3/301 (1%)	3	3/305 (1%)	3
Agitation	1/301 (0.3%)	1	2/305 (0.7%)	2
Anger	0/301 (0%)	0	1/305 (0.3%)	1
Anorgasmia	1/301 (0.3%)	1	1/305 (0.3%)	1
Anxiety	3/301 (1%)	4	3/305 (1%)	3
Anxiety disorder	0/301 (0%)	0	1/305 (0.3%)	1
Bruxism	1/301 (0.3%)	1	0/305 (0%)	0
Confusional state	1/301 (0.3%)	1	1/305 (0.3%)	1
Depression	0/301 (0%)	0	1/305 (0.3%)	1
Elevated mood	1/301 (0.3%)	1	0/305 (0%)	0
Initial insomnia	1/301 (0.3%)	1	0/305 (0%)	0
Insomnia	4/301 (1.3%)	4	4/305 (1.3%)	4
Libido decreased	0/301 (0%)	0	1/305 (0.3%)	1
Mood altered	1/301 (0.3%)	1	0/305 (0%)	0
Mood swings	2/301 (0.7%)	2	0/305 (0%)	0
Nervousness	2/301 (0.7%)	2	0/305 (0%)	0
Nightmare	1/301 (0.3%)	1	1/305 (0.3%)	1
Restlessness	1/301 (0.3%)	1	0/305 (0%)	0
Sleep disorder	1/301 (0.3%)	1	0/305 (0%)	0
Stress	0/301 (0%)	0	1/305 (0.3%)	1
Renal and urinary disorders
Micturition urgency	1/301 (0.3%)	1	0/305 (0%)	0
Pollakiuria	1/301 (0.3%)	1	0/305 (0%)	0
Reproductive system and breast disorders
Breast pain	0/301 (0%)	0	1/305 (0.3%)	1
Vaginal haemorrhage	3/301 (1%)	3	1/305 (0.3%)	1
Vulvovaginal discomfort	0/301 (0%)	0	1/305 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	4/301 (1.3%)	4	0/305 (0%)	0
Nasal congestion	0/301 (0%)	0	3/305 (1%)	3
Nasal dryness	1/301 (0.3%)	1	0/305 (0%)	0
Oropharyngeal blistering	1/301 (0.3%)	1	0/305 (0%)	0
Oropharyngeal pain	3/301 (1%)	3	1/305 (0.3%)	1
Pulmonary congestion	1/301 (0.3%)	1	0/305 (0%)	0
Respiratory disorder	2/301 (0.7%)	2	0/305 (0%)	0
Rhinitis allergic	2/301 (0.7%)	2	0/305 (0%)	0
Rhinorrhoea	1/301 (0.3%)	1	0/305 (0%)	0
Sinus congestion	0/301 (0%)	0	2/305 (0.7%)	2
Sneezing	1/301 (0.3%)	1	0/305 (0%)	0
Throat irritation	2/301 (0.7%)	2	0/305 (0%)	0
Upper-airway cough syndrome	2/301 (0.7%)	2	0/305 (0%)	0
Yawning	1/301 (0.3%)	1	0/305 (0%)	0
Skin and subcutaneous tissue disorders
Acne	1/301 (0.3%)	1	0/305 (0%)	0
Alopecia	1/301 (0.3%)	1	1/305 (0.3%)	1
Dermatitis	1/301 (0.3%)	1	1/305 (0.3%)	1
Hyperhidrosis	3/301 (1%)	3	2/305 (0.7%)	2
Pruritus	1/301 (0.3%)	1	0/305 (0%)	0
Pruritus generalised	0/301 (0%)	0	1/305 (0.3%)	1
Rash	2/301 (0.7%)	2	1/305 (0.3%)	1
Skin disorder	0/301 (0%)	0	1/305 (0.3%)	1
Skin lesion	1/301 (0.3%)	1	1/305 (0.3%)	1
Sweat gland disorder	3/301 (1%)	3	2/305 (0.7%)	2
Urticaria	0/301 (0%)	0	1/305 (0.3%)	1
Surgical and medical procedures
Cataract operation	0/301 (0%)	0	1/305 (0.3%)	1
Endodontic procedure	1/301 (0.3%)	1	0/305 (0%)	0
Mole excision	0/301 (0%)	0	1/305 (0.3%)	1
Scar excision	0/301 (0%)	0	1/305 (0.3%)	1
Vascular disorders
Hot flush	2/301 (0.7%)	2	0/305 (0%)	0
Hypertension	3/301 (1%)	3	0/305 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.