24-week Placebo-controlled Trial of Flibanserin Once Daily in Premenopausal Women With Hypoactive Sexual Desire Disorder

A Twenty Four Week, Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Trial of Flibanserin 50mg Every Evening and Flibanserin 100mg Every Evening in Women With Hypoactive Sexual Desire Disorder in North America

This trial is designed to assess the safety and efficacy of flibanserin in the treatment of premenopausal women with Hypoactive Sexual Desire Disorder (HSDD) that meets standard diagnostic criteria. Efficacy for flibanserin will be assessed vs. a parallel placebo group.

Study Overview

• Status: Completed
• Conditions: Sexual Dysfunctions, Psychological
• Intervention / Treatment: Drug: flibanserin

Detailed Description

This trial was designed as a prospective, multicenter trial containing a 24-week, randomized, double blind, placebo controlled, parallel-group period that assessed the effects of flibanserin (maximum total daily dose: 100 mg q.d.) compared with placebo in premenopausal women with HSDD, determined by Diagnostic and Statistical Manual IV- Text Revision (DSM IV-TR®) criteria. Three hundred patients were to be randomized to each treatment group. This trial examined the safety and efficacy of flibanserin compared to placebo for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 880
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • 511.71.02002 Boehringer Ingelheim Investigational Site
  • British Columbia
    • Kelowna, British Columbia, Canada
      • 511.71.02006 Boehringer Ingelheim Investigational Site
    • Surrey, British Columbia, Canada
      • 511.71.02011 Boehringer Ingelheim Investigational Site
    • Vancouver, British Columbia, Canada
      • 511.71.02007 Boehringer Ingelheim Investigational Site
    • Victoria, British Columbia, Canada
      • 511.71.02008 Boehringer Ingelheim Investigational Site
    • Victoria, British Columbia, Canada
      • 511.71.02012 Boehringer Ingelheim Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • 511.71.02010 Boehringer Ingelheim Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • 511.71.02001 Boehringer Ingelheim Investigational Site
  • Ontario
    • Burlington, Ontario, Canada
      • 511.71.02004 Boehringer Ingelheim Investigational Site
    • London, Ontario, Canada
      • 511.71.02013 Boehringer Ingelheim Investigational Site
    • Oshawa, Ontario, Canada
      • 511.71.02009 Boehringer Ingelheim Investigational Site
    • Ottawa, Ontario, Canada
      • 511.71.02003 Boehringer Ingelheim Investigational Site
  • Quebec
    • Montréal, Quebec, Canada
      • 511.71.02005 Boehringer Ingelheim Investigational Site
    • Québec, Quebec, Canada
      • 511.71.02014 Boehringer Ingelheim Investigational Site
• United States
  • Alabama
    • Mobile, Alabama, United States
      • 511.71.01034 Boehringer Ingelheim Investigational Site
    • South Birmingham, Alabama, United States
      • 511.71.01042 Boehringer Ingelheim Investigational Site
  • Arizona
    • Phoenix, Arizona, United States
      • 511.71.01016 Boehringer Ingelheim Investigational Site
  • California
    • La Mesa, California, United States
      • 511.71.01041 Boehringer Ingelheim Investigational Site
    • San Diego, California, United States
      • 511.71.01011 Boehringer Ingelheim Investigational Site
    • Westlake Village, California, United States
      • 511.71.01027 Boehringer Ingelheim Investigational Site
  • Colorado
    • Denver, Colorado, United States
      • 511.71.01035 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Groton, Connecticut, United States
      • 511.71.01010 Boehringer Ingelheim Investigational Site
    • New Britain, Connecticut, United States
      • 511.71.01021 Boehringer Ingelheim Investigational Site
  • Delaware
    • Newark, Delaware, United States
      • 511.71.01037 Boehringer Ingelheim Investigational Site
  • Florida
    • Boynton Beach, Florida, United States
      • 511.71.01001 Boehringer Ingelheim Investigational Site
    • Clearwater, Florida, United States
      • 511.71.01032 Boehringer Ingelheim Investigational Site
    • Miami, Florida, United States
      • 511.71.01014 Boehringer Ingelheim Investigational Site
    • Pembroke Pines, Florida, United States
      • 511.71.01025 Boehringer Ingelheim Investigational Site
    • Plantation, Florida, United States
      • 511.71.01006 Boehringer Ingelheim Investigational Site
  • Georgia
    • Atlanta, Georgia, United States
      • 511.71.01015 Boehringer Ingelheim Investigational Site
    • Marietta, Georgia, United States
      • 511.71.01038 Boehringer Ingelheim Investigational Site
  • Illinois
    • Chicago, Illinois, United States
      • 511.71.01036 Boehringer Ingelheim Investigational Site
  • Indiana
    • Evansville, Indiana, United States
      • 511.71.01029 Boehringer Ingelheim Investigational Site
    • Renton, Indiana, United States
      • 511.71.01028 Boehringer Ingelheim Investigational Site
  • Louisiana
    • New Orlean, Louisiana, United States
      • 511.71.01024 Boehringer Ingelheim Investigational Site
  • Maryland
    • Towson, Maryland, United States
      • 511.71.01040 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • Brighton, Massachusetts, United States
      • 511.71.01045 Boehringer Ingelheim Investigational Site
  • Missouri
    • St. Louis, Missouri, United States
      • 511.71.01005 Boehringer Ingelheim Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • 511.71.01030 Boehringer Ingelheim Investigational Site
  • New York
    • Bronx, New York, United States
      • 511.71.01012 Boehringer Ingelheim Investigational Site
    • Rochester, New York, United States
      • 511.71.01007 Boehringer Ingelheim Investigational Site
  • North Carolina
    • New Bern, North Carolina, United States
      • 511.71.01023 Boehringer Ingelheim Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States
      • 511.71.01002 Boehringer Ingelheim Investigational Site
    • Cincinnati, Ohio, United States
      • 511.71.01044 Boehringer Ingelheim Investigational Site
    • Columbus, Ohio, United States
      • 511.71.01026 Boehringer Ingelheim Investigational Site
  • Oklahoma
    • Edmond, Oklahoma, United States
      • 511.71.01039 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Danville, Pennsylvania, United States
      • 511.71.01003 Boehringer Ingelheim Investigational Site
    • Philadelphia, Pennsylvania, United States
      • 511.71.01033 Boehringer Ingelheim Investigational Site
    • Pittsburgh, Pennsylvania, United States
      • 511.71.01031 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Mt. Pleasant, South Carolina, United States
      • 511.71.01022 Boehringer Ingelheim Investigational Site
  • Tennessee
    • Germantown, Tennessee, United States
      • 511.71.01020 Boehringer Ingelheim Investigational Site
  • Texas
    • San Antonio, Texas, United States
      • 511.71.01017 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 511.71.01018 Boehringer Ingelheim Investigational Site
  • West Virginia
    • Huntington, West Virginia, United States
      • 511.71.01008 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women who are 18 years of age and older.
2. Premenopausal women having regular menstrual periods who have HSDD (decreased sexual desire), generalized acquired type, according to DSM IV-TR criteria.
3. Patient must meet minimum cut-off scores on questionnaires relating to sexual functioning and sexual distress.
4. Patients must be willing to try to have sexual activity (e.g., any act involving direct genital stimulation) at least once monthly.
5. Patients must be willing and able to use an electronic diary (eDiary) on a daily basis (e.g., have access to a working land line telephone for daily data transmissions).
6. At the Baseline Visit, patients must have complied with eDiary use adequately.
7. Patients must be in a stable, monogamous, heterosexual relationship that is secure and communicative, for at least 1 year prior to the Screen Visit. The partner is expected to be physically present at least 50% of each month.
8. Patients must have used a medically acceptable method of contraception for at least 3 months before the Baseline Visit (Visit 2) and continue to use that medically acceptable method of contraception during the trial.
9. In the investigators opinion, patients must be reliable, honest, compliant, and agree to co-operate with all trial evaluations as well as to be able to perform them.
10. Patients must be able and willing to give meaningful, written informed consent prior to participation in the trial, in accordance with regulatory requirements. Patients must have sufficient understanding to communicate effectively with the investigator, and be willing to discuss their sexual functioning with the investigative staff.
11. Patients must have a clinically acceptable Pap smear as read by a cytology facility (no evidence of malignancy or squamous intraepithelial lesions) within 6 months before the Screen Visit.

Exclusion Criteria:

1. Patients who have taken any medication noted in the protocols List of Prohibited Medications within 30 days before screening.
2. Patients whose sexual function was affected (enhanced or worsened) in the investigators opinion by any medication within 30 days before the Screen Visit and anytime prior to the Baseline Visit.
3. Patients with a history of drug dependence or abuse within the past one year.
4. Patients with a history of multiple severe reactions (i.e., allergic or oversensitivity to usual doses) to drugs that affect the brain.
5. Patients with a history of participation in a trial of another investigational medication within one month prior to the Screen Visit, or participation in any previous clinical trial of flibanserin.
6. Patients who meet accepted diagnostic criteria for sexual disorders that would interfere with improvement in HSDD (sexual aversion, substance-induced sexual problems, urge to live as a man, etc.
7. Patients who indicate that their sexual partner has inadequately treated sexual problems that could interfere with the patients response to treatment.
8. Patients who have entered the menopausal transition or menopause or have had a hysterectomy.
9. Patients with findings at the Screen Visit of infection, inflammation, undue tenderness, or shrinkage (atrophy) of the female organs.
10. Patients who are breast feeding or have breastfed within the last 6 months prior to the Baseline Visit.
11. Patients who are pregnant or have been pregnant within the last 6 months prior to the Baseline Visit.
12. Patients with a history of Major Depressive Disorder within 6 months prior the Screen Visit, a score indicating depression on a depression scale, a history of suicide attempt, or current suicidal ideation evident at the Screen or Baseline Visit.
13. Patients with a history of any other psychiatric disorders that could impact sexual function, risks patients safety, or may impact compliance.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: fibanserin; flibanserin 50 mg q.h.s.	Drug: flibanserin; flibanserin placebo versus 50 mg qhs versus 100 mg qhs; Other Names: placebo; flibanserin 50 mg; flibanserin 100mg
EXPERIMENTAL: flibanserin; flibanserin 100 mg q.h.s.	Drug: flibanserin; flibanserin placebo versus 50 mg qhs versus 100 mg qhs; Other Names: placebo; flibanserin 50 mg; flibanserin 100mg
PLACEBO_COMPARATOR: placebo; placebo q.h.s.	Drug: flibanserin; flibanserin placebo versus 50 mg qhs versus 100 mg qhs; Other Names: placebo; flibanserin 50 mg; flibanserin 100mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satisfying Sexual Event Monthly Change From Baseline at Final Visit	Change from baseline in the frequency of sexual satisfying events, as measured via e-Diary, standardized to a 28-day period. Change from baseline is calculated as the difference between the four week baseline period and Week 21 to Week 24.	Baseline, Week 24
Sexual Desire Monthly Change on Electronic Diary From Baseline at Final Visit	Change from baseline in eDiary Sexual Desire Monthly Total Score standardized to a 28-day period. Change from baseline calculated as the difference between the 4 week baseline period and Week 21 to Week 24. Patients recorded information daily throughout trial. Every time the eDiary was completed, a desire question was asked. If a patient did not complete the diary on a given day, the patient was not asked to enter desire information for more than a 24-hour retrospective period. The desire item read "Indicate your most intense level of sexual desire in the last 24 hours/since your last visit." Potential responses included "no," "low," "moderate," or "strong", scored 0-3 (0 indicating no desire and 3 indicating the highest level of desire): 0 = No desire; = Low desire; = Moderate desire; = Strong desire Total score ranged from 0-84, with higher scores reflecting stronger desire). Monthly desire score was calculated as 28 x (sum of daily desire scores/number of responses).	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Female Sexual Distress Scale - Revised (FSDS-R) Total Score Change From Baseline at Final Visit	Change from baseline in the Female Sexual Distress Scale - revised (FSDS-R) Total Score with a seven day recall period. The FSDS is a measure of female personal distress associated with sexual dysfunction. Reliability and validity of the FSDS (12-item version) has been evaluated in different samples of sexually functional and dysfunctional women. An additional question (Question 13) was added to the validated FSDS© in order to capture distress related to specifically sexual desire so that this domain could be appropriately captured. FSDS plus Question 13 comprises FSDS-R, thus making the FSDS-R a self-administered 13 item questionnaire. The maximum total score of the FSDS-R is '52' (score of minimum of 0 and maximum of 4 for each item) and indicates the maximum level of sexual distress (the higher the score, the higher the level of reported sexual desire).	Baseline, Week 24
Female Sexual Distress Scale - Revised (FSDS-R) Question 13 Score Change From Baseline at Final Visit	Change from baseline in the FSDS-R Question 13 (Bothered by low sexual desire). The FSDS is a measure of female personal distress associated with sexual dysfunction. Reliability and validity of the FSDS (12-item version) has been evaluated in different samples of sexually functional and dysfunctional women. An additional question (Question 13) was added to the validated FSDS© in order to capture distress related to specifically sexual desire so that this domain could be appropriately captured. FSDS plus Question 13 comprises FSDS-R, thus making the FSDS-R a self-administered 13 item questionnaire. The scoring for item 13 is from 0-4, with 4 indicating the highest level of sexual distress.	Baseline, Week 24
Female Sexual Functioning Index (FSFI) Desire Domain Score Change From Baseline at Final Visit	Female Sexual Function Inventory (FSFI) Desire Domain assesses sexual desire or interest with 2 questions ranging from 1 (very low) to 5 (very high). The domain total score is multiplied by 0.6 yielding scores ranging from 1.2 to 6 (higher scores = higher level of desire or interest).	Baseline, Week 24
Female Sexual Functioning Index (FSFI) Total Score Change From Baseline at Final Visit	The FSFI© is a self-administered questionnaire to assess FSD, which consists of 19 questions that are scored from '0' to '5.' The scale contains six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain. Higher scores indicate higher levels of the domain assessed. The total score is a weighted average of the six domains, each contributing a maximum of 6 points to the total, so the minimum score is 2, while the maximum score of FSFI© is 36.	Baseline, Week 24
Patient Benefit Evaluation	The Patient Benefit Evaluation is a single question asking the patient whether or not she experienced a meaningful benefit from the study medication during the trial. This question ("Overall, do you believe that you have experienced a meaningful benefit from the study medication?") was asked upon treatment discontinuation.	Week 24

Collaborators and Investigators

• Sponsor: Sprout Pharmaceuticals, Inc

Publications and helpful links

General Publications

• Derogatis LR, Komer L, Katz M, Moreau M, Kimura T, Garcia M Jr, Wunderlich G, Pyke R; VIOLET Trial Investigators. Treatment of hypoactive sexual desire disorder in premenopausal women: efficacy of flibanserin in the VIOLET Study. J Sex Med. 2012 Apr;9(4):1074-85. doi: 10.1111/j.1743-6109.2011.02626.x. Epub 2012 Jan 16.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): April 1, 2008

Study Registration Dates

• First Submitted: August 3, 2006
• First Submitted That Met QC Criteria: August 3, 2006
• First Posted (ESTIMATE): August 4, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): June 27, 2016
• Last Update Submitted That Met QC Criteria: June 6, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological
• Other Study ID Numbers: 511.71; VIOLET (Boehringer Ingelheim)