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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Noven Therapeutics
ClinicalTrials.gov Identifier:
NCT00786188
First received: November 4, 2008
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

This is an exploratory 8-week, multicenter, double-blind, randomized, placebo-controlled study of Brisdelle (paroxetine mesylate) Capsules 7.5 mgin subjects with moderate to severe postmenopausal vasomotor symptoms (VMS), defined as follows:

  • Moderate VMS: Sensation of heat with sweating, able to continue activity
  • Severe VMS: Sensation of heat with sweating, causing cessation of activity

Condition Intervention Phase
Hot Flashes
Drug: Brisdelle (paroxetine mesylate)
Drug: Sugar pill
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 2, Exploratory, Eight-Week, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Efficacy and Safety Study of Mesafem (Paroxetine Mesylate) Capsules in the Treatment of Vasomotor Symptoms Associated With Menopause

Resource links provided by NLM:


Further study details as provided by Noven Therapeutics:

Primary Outcome Measures:
  • Mean Change From Baseline in Hot Flash Frequency at Week 4 and Week 8 [ Time Frame: Week 4 and Week 8 ] [ Designated as safety issue: No ]

    The number of hot flashes reported in the result table are:

    • Mean change in frequency of moderate to severe VMS from baseline to Week 4
    • Mean change in frequency of moderate to severe VMS from baseline to Week 8. They are both measured as hot flashes per week.

  • Mean Change From Baseline in Hot Flash Severity at Week 4 and Week 8 [ Time Frame: Week 4 and Week 8 ] [ Designated as safety issue: No ]

    A scale was not used to measure severity scores. Severity scores of hot flashes were calculated for each subject. The following formula was used to calculate severity.

    SS = (2•Fm + 3•Fs) ÷ (Fm + Fs)

    Where:

    SS = severity score Fm = frequency of moderate hot flashes Fs = frequency of severe hot flashes The mean number of moderate and severe hot flashes that was recorded in the Run-In Period was used to calculate the baseline severity score.



Secondary Outcome Measures:
  • Change From Baseline in Climacteric Symptoms at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]

    The Greene Climacteric Scale (GCS) was used for this measurement. The scale has 21 questions and measures symptoms in 4 areas; these are psychological (anxiety and depression), physical, vasomotor, and libido.

    The severity of the symptom was scored as: 0=none, 1=mild, 2=moderate, and 3=severe. Anxiety was determined by using the sum of scores 1 to 6, and depression was determined by using the sum of scores 7 to 11. Physical aspects were determined by using the sum of scores 12 to 18; vasomotor aspects were determined by using the sum of scores 19 to 20; and libido was determined by using the score for question 21.

    The total GCS score ranges from "0" to "63" which is the sum of all the scores for the 21-symptom assessment questions in this scale. Each subject's total GCS score at baseline and at Week 8 were used to calculate change from baseline in these symptoms. The change from baseline is reported below.


  • Change From Baseline in Hot Flash Composite Score at Week 4 and Week 8 [ Time Frame: Week 4 and Week 8 ] [ Designated as safety issue: No ]

    A scale was not used for this measurement.

    Composite scores of hot flashes were calculated by using the following formula:

    CS = (2 • Fm + 3 • Fs)

    Where:

    CS = composite score Fm = frequency of moderate hot flashes Fs = frequency of severe hot flashes The mean number of moderate and severe hot flashes recorded in the Run-In Period was used to calculate the baseline composite score.


  • Effect of Brisdelle (Paroxetine Mesylate) Capsules on Depression and Anxiety at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]

    Depression & anxiety were measured using the Hospital Anxiety & Depression Scale (HADS).

    The HADS is a scale developed to assess anxiety & depression. The HADS Scale consists of 14 Questions (7 relating to anxiety; 7 relating to depression) with possible scores ranging from 0 to 21.

    The results presented below are the number of participants with abnormal HADS Scores for both Abnormal Anxiety & Abnormal Depression combined at Week 8.


  • Effect of Brisdelle (Paroxetine Mesylate) Capsules on Mood at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

    Mood was measured using the Profile of Mood States (POMS) Questionnaire. The Profile of Moods States (POMS) is a 65-item multi-dimensional measure that provides a method of assessing transient, fluctuating active mood states. Key areas that are measured include: tension-anxiety, anger-hostility, fatigue-inertia, depression-dejection, vigor-activity, confusion-bewilderment. Responses to questions are scored with the following numerical values: Not at all = 1, A little = 2, Moderate = 3, Quite a bit = 4, Extremely = 5. A total score for a domain was obtained by summing the responses of individual items in the domain. The total POMS score can range from "65" to "335."

    The percentage of participants who had a change from baseline in the total score at Week 4 is reported below.


  • Effect of Brisdelle (Paroxetine Mesylate) Capsules on Improvement of Hot Flash Interference at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

    Interference of hot flashes was measured by using the Hot Flash-Related Daily Interference Scale (HFRDIS). The HFRDIS is a 10-item scale that measures the degree to which hot flashes interfere with 9 daily activities and the tenth item measures the degree to which hot flashes interfere with each of the other items. Subjects can score for each item on a scale from 0 to 10 where 0 = Do not interfere and a score of 10 = Completely interferes.

    The measure being reported below is percentage of responders who had an improvement in HFRDIS score at Week 4 compared to baseline. A responder is defined as a subject who had an improvement in the HFRDIS score. An improvement is define as a score ≤3 on each question.


  • Proportion of Clinical Global Impression (CGI) Responders at Week 4 and Week 8 [ Time Frame: Week 4 and Week 8 ] [ Designated as safety issue: No ]
    The Clinical Global Impression Scale (CGIS) was completed by the investigator and was used to measure the severity of the VMS at any given time and the improvement from baseline. Responders were defined as subjects who achieved a score of 1 to 3 where 1 = very much improved, 2 = much improved, and 3 = minimally improved. Non-responders were defined as subjects who achieved a score of 4 to 7 where 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

  • Asses the Effect of Brisdelle (Paroxetine Mesylate) Capsules on the Interference on Sexual Functioning at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
    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.

  • Proportion of Numerical Rating Scale (NRS) True Responders at Week 4 and Week 8 [ Time Frame: Week 4 and Week 8 ] [ Designated as safety issue: No ]

    The Subject Impression Numerical Rating Scale (NRS) is an 11-point scale was used to measure how bothered a subject was by hot flashes both during the day and the night.

    The measure being reported below is percentage of responders who had an improvement in NRS score at Week 4 compared to baseline. A responder is defined as a subject who had an improvement in the NRS score. An improvement is define as a score ≤3 on each question.


  • Effect of Brisdelle (Paroxetine Mesylate) Capsules on BMI at Week 4 and Week 8 [ Time Frame: Week 4 and Week 8 ] [ Designated as safety issue: No ]
    Body Mass Index (BMI) was calculated by using height in centimeters and weight in kilograms.


Enrollment: 102
Study Start Date: November 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Brisdelle (paroxetine mesylate)
Eligible subjects will be randomized to receive Brisdelle (paroxetine mesylate) Capsules 7.5 mg.
Drug: Brisdelle (paroxetine mesylate)
Eligible subjects will be randomized to receive Brisdelle™ (paroxetine mesylate) Capsules 7.5 mg.
Other Names:
  • Former Names: Mesafem capsules 7.5 mg or
  • LDMP (Low-Dose Mesylate salt of Paroxetine)
Placebo Comparator: Placebo - Sugar Pill
Eligible subjects will be randomized to receive a sugar pill.
Drug: Sugar pill
Subjects will receive a sugar pill.
Other Name: Sugar pill

Detailed Description:

Eligible subjects will be entered into a 1-week observation period followed by a 1-week run-in period. Following completion of the run-in period, eligible subjects will be randomized to receive either Brisdelle (paroxetine mesylate) Capsules 7.5 mg or placebo in a 1:1 ratio. Study drug will be administered once daily at bedtime. Symptom assessment questionnaires will be administered at baseline and at Day 28 and Day 57 visits.

  Eligibility

Ages Eligible for Study:   41 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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. History of hypersensitivity or adverse reaction to paroxetine mesylate
  2. Use of an investigational study medication within 30 days prior to screening or during the study
  3. Concurrent participation in another clinical trial or previous participation in this trial
  4. Family of investigational-site staff
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00786188

Locations
United States, Florida
Altus Research
Lake Worth, Florida, United States, 33461
Anchor Research Center
Naples, Florida, United States, 34102
United States, North Carolina
Hawthorne Research
Greensboro, North Carolina, United States, 27408
Hawthorne Medical Research, Inc.
Winston-Salem, North Carolina, United States, 27103
United States, Pennsylvania
Philadelphia Clinical Research
Philadelphia, Pennsylvania, United States, 19114
United States, Tennessee
Chattanooga Medical Research, LLC
Chattanooga, Tennessee, United States, 37404
United States, Virginia
National Clinical Research, Inc.
Richmond, Virginia, United States, 23294
Virginia Women's Center
Richmond, Virginia, United States, 23233
United States, Washington
Women's Clinical Research Center
Seattle, Washington, United States, 98105
North Spokane Women's Clinic Research
Spokane, Washington, United States, 99207
Sponsors and Collaborators
Noven Therapeutics
Investigators
Principal Investigator: Patrick F. Freuen, MD North Spokane Women's Clinic, Spokane, WA 99207
Principal Investigator: Richard E. Hedrick, MD Hawthorne Medical Research, Inc., Winston-Salem, NC 27103
Principal Investigator: Samuel N. Lederman, MD Altus Research, Lake Worth, FL 33461
Principal Investigator: Larry S. Seidman, DO Philadelphia Clinical Research, LLC, Philadelphia, PA 19114
Principal Investigator: James E. Tomblin, MD Hawthorne Medical Research, Inc., Greensboro, NC 27408
Principal Investigator: Peter A. Zedler, MD Virginia Women's Center, Richmond, VA 23233
Principal Investigator: D. S. Harnsberger, MD Chattanooga Medical Research, LLC, Chattanooga, TN 37404
Principal Investigator: John A. Hoekstra, MD National Clinical Research, Inc., Richmond, VA 23294
Principal Investigator: Robin Kroll, MD Women's Clinical Research Center, Seattle, WA 98105
Principal Investigator: Ashley Tunkle, MD Anchor Research Center, Naples, FL 34102
  More Information

Publications:
Responsible Party: Noven Therapeutics
ClinicalTrials.gov Identifier: NCT00786188     History of Changes
Other Study ID Numbers: N30-002
Study First Received: November 4, 2008
Results First Received: July 16, 2013
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Noven Therapeutics:
Menopause
Vasomotor Symptoms
Hot flash
Perimenopause
Nonhormonal therapies
Climacteric symptoms
Mesafem
Low-Dose Mesylate salt of Paroxetine (LDMP)

Additional relevant MeSH terms:
Hot Flashes
Signs and Symptoms
Contraceptives, Oral
Paroxetine
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 20, 2014