Clinical trial NCT01101841: 24-Week Efficacy & Safety Study of Brisdelle™ (Formerly Known as Mesafem) in the Treatment of Vasomotor Symptoms
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hot Flashes
Keywords: Vasomotor Symptoms
Menopause
Hot Flashes
Perimenopause
Nonhormonal therapies
Climacteric symptoms
Mesafem
Low-Dose Mesylate salt of Paroxetine (LDMP)
Lead sponsor: Noven Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-04-12
Enrollment: 570
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 12.
timeFrame: Week 4 and Week 12
measure: Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 12.
timeFrame: Week 4 and Week 12
Secondary outcomes:
measure: Percent Persistence of Benefit, Statistically Significant Difference in Having 50% or More Reduction Compared to Baseline at Week 24.
timeFrame: Week 24
measure: Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI <32 kg/m2, Week 4 and Week 12), Median
timeFrame: Week 4 and Week 12
measure: Change From Baseline in Total Number of Awakenings Due to Hot Flashes, Median
timeFrame: Week 4 and Week 12
measure: Change in Frequency of Moderate to Severe Hot Flashes Frequency From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median
timeFrame: Week 4 and Week 12
measure: Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI <32 kg/m2, At Week 4 and Week 12), Median
timeFrame: Week 4 and Week 12
measure: Change in Severity of Moderate to Severe Hot Flashes From Baseline (BMI ≥32 kg/m2, Week 4 and Week 12), Median
timeFrame: Week 4 and Week 12
measure: Change From Baseline in Greene Climacteric Scale (GCS) at Week 4 and Week 12, Total Score, Median
timeFrame: Week 4 and Week 12
measure: Percentage of Responders
timeFrame: Week 4 and Week 12
measure: Percent Daytime and Nighttime Responders, Numerical Rating Scale (NRS)
timeFrame: Week 4 and Week 12
measure: Change From Baseline in Arizona Sexual Experience Scale (ASEX, Week 4 and Week 12) Total Score, Median
timeFrame: Week 4 and Week 12
measure: 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)
timeFrame: Week 4 and Week 12
measure: Percent Responders Improvement in VMS From Baseline Using the Clinical Global Impression (CGI) Scale.
timeFrame: Week 4 and Week 12
measure: Effect of Brisdelle (Paroxetine Mesylate) Capsules on Anxiety and Depression
timeFrame: Week 4 and Week 12
measure: Assessment of Mood
timeFrame: Week 4 and Week 12
measure: BMI Change From Baseline (kg/m2), Median
timeFrame: Week 4 and Week 12
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Montgomery Women's Health Associates, PC
state: Alabama
city: Chandler
country: United States
facility: East Valley Family Physicians PLC
state: Arizona
city: San Diego
country: United States
facility: Genesis Center For Clinical Research
state: California
city: Santa Ana
country: United States
facility: Apex Research Institute
state: California
city: Denver
country: United States
facility: Downtown Women's Health Care
state: Colorado
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Boynton Beach
country: United States
facility: Visions Clinical Research
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Clearwater
country: United States
facility: Women's Medical Research Group, LLC
state: Florida
city: Lake Worth
country: United States
facility: Altus Research
state: Florida
city: Naples
country: United States
facility: Anchor Research Center
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials, LLC
state: Florida
city: Decatur
country: United States
facility: Soapstone Center for Clinical Research
state: Georgia
city: Sandy Springs
country: United States
facility: Mount Vernon Clinical Research, LLC
state: Georgia
city: Lincoln
country: United States
facility: Women's Clinic of Lincoln, PC
state: Nebraska
city: Moorestown
country: United States
facility: Phoenix Ob-Gyn Associates, LLC
state: New Jersey
city: Rochester
country: United States
facility: Rochester Clinical Research
state: New York
city: Greensboro
country: United States
facility: Hawthorne Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Hawthorne Medical Research, Inc.
state: North Carolina
city: Columbus
country: United States
facility: Columbus Center for Women's Health Research
state: Ohio
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia Clinical Research
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Clinical Trials Research Services, LLC
state: Pennsylvania
city: Columbia
country: United States
facility: SC Clinical Research Center, LLC
state: South Carolina
city: Mt. Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Medical Research, LLC
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
city: Houston
country: United States
facility: The Woman's Hospital of Texas Clinical Research Center
state: Texas
city: Richmond
country: United States
facility: Virginia Women's Center
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research, Inc.
state: Virginia
city: Seattle
country: United States
facility: Women's Clinical Research Center
state: Washington
city: Spokane
country: United States
facility: North Spokane Women's Clinic Research
state: Washington
Study officials:
affiliation: North Spokane Women's Clinic Research, Spokane, WA 99207
name: Derrick R Havin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hawthorne Medical Research, Inc., Winston-Salem, NC 27103
name: Richard E Hedrick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Altus Research, Lake Worth, FL 33461
name: Samuel N Lederman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Philadelphia Clinical Research, LLC, Philadelphia, PA 19114
name: Larry S Seidman, DO
role: PRINCIPAL_INVESTIGATOR
affiliation: Hawthorne Medical Research, Inc., Greensboro, NC 27408
name: James E Tomblin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Women's Center, Richmond, VA 23233
name: Peter A Zedler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chattanooga Medical Research, LLC, Chattanooga, TN 37404
name: D S Harnsberger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Clinical Research, Inc., Richmond, VA 23294
name: John A Hoekstra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women's Clinical Research Center, Seattle, WA 98105
name: Robin Kroll, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Anchor Research Center, Naples, FL 34102
name: Ashley Tunkle, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rochester Clinical Research, Rochester, NY 14609
name: Matthew Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: East Valley Family Physicians PLC, Chandler, AZ 85224
name: Donna DeSantis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Genesis Center For Clinical Research, San Diego, CA 92103
name: Steven Drosman
role: PRINCIPAL_INVESTIGATOR
affiliation: Meridien Research, Brooksville, FL 34601
name: Mildred Farmer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Woman's Hospital of Texas Clinical Research Center, Houston, TX 77054
name: Sandra Hurtado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Phoenix Ob-Gyn Associates, LLC, Moorestown, NJ 08057
name: Bruce Levine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Soapstone Center for Clinical Research, Decatur, GA 30034
name: Tyrone Malloy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Apex Research Institute, Santa Ana, CA 92705
name: Eric Ross, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Coastal Carolina Research Center, Mt. Pleasant, SC 29464
name: Cynthia Strout, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Downtown Women's Health Care, Denver, CO, 80218
name: Arthur Waldbaum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women's Medical Research Group, LLC, Clearwater, FL 33759
name: Edward Zbella, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montgomery Women's Health Associates, PC, Montgomery, AL 36116
name: James R Dockery, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Vernon Clinical Research, LLC, Sandy Springs, GA 30328
name: Stephen C Blank, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Visions Clinical Research, Boynton Beach, FL 33472
name: Keith Aqua, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Trials Research Services, LLC, Pittsburgh, PA 15206
name: Saul R Berg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Clinical Trial Center, LLC, Jenkintown, PA 19046
name: Marvin Kalafer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbus Center for Women's Health Research, Columbus, Ohio 43213
name: David J Portman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Women's Clinic of Lincoln, PC, Lincoln, NE 68510
name: Stephen Swanson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chase Medical Research, LLC, Waterbury, CT 06708
name: Joseph Soufer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Associates, Inc., Nashville, TN 37203
name: ShaH R Scott, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SC Clinical Research Center, LLC, Columbia, SC 29201
name: Mary K Neuffer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Comprehensive Clinical Trials, LLC, West Palm Beach, FL 33409
name: Ronald Ackerman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fugate SE, Church CO. Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother. 2004 Sep;38(9):1482-99. doi: 10.1345/aph.1D610. Epub 2004 Aug 3.
citation: Kritz-Silverstein D, Goldani Von Muhlen 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. doi: 10.1089/15246090050147727.
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. doi: 10.1001/jama.295.17.2057.
citation: Greene JG. A factor analytic study of climacteric symptoms. J Psychosom Res. 1976;20(5):425-30. doi: 10.1016/0022-3999(76)90005-2. No abstract available.
citation: Pinkerton JV, Joffe H, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause. 2015 Jan;22(1):50-8. doi: 10.1097/GME.0000000000000311.
citation: Portman DJ, Kaunitz AM, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause. Menopause. 2014 Oct;21(10):1082-90. doi: 10.1097/GME.0000000000000210.
citation: Simon JA, Portman DJ, Kaunitz AM, Mekonnen H, Kazempour K, Bhaskar S, Lippman J. Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause. 2013 Oct;20(10):1027-35. doi: 10.1097/GME.0b013e3182a66aa7.