Study Evaluating The Safety And Efficacy Of Desvenlafaxine Succinate For Vasomotor Symptoms In Menopausal Women

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of Desvenlafaxine Succinate (DVS) Sustained Release (SR), in comparison to placebo for the treatment of Vasomotor Symptoms (VMS) in menopausal women.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study Assessing The Safety And Efficacy Of DVS SR For The Treatment Of Vasomotor Symptoms Associated With Menopause

Conditions
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Vasomotor Symptoms

Intervention / Treatment
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* Drug: desvenlafaxine succinate (DVS) SR
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy, postmenopausal women who seek treatment for hot flushes Body Mass Index (BMI) less than or equal to 34 kg/m^2 Exclusion Criteria: Hypersensitivity to Venlafaxine Myocardial infarction an/or unstable angina within 6 months of screening History of seizure disorder

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>desvenlafaxine succinate (DVS) SR | Drug: desvenlafaxine succinate (DVS) SR<br>* Titration with 50 mg tablets once daily for 7 days, then 100mg tablets once daily from day 8 to day 365, then taper with 50 mg tablets once daily for 7 days, followed by 25 mg tablets once daily for 7 days.<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo<br>* Titration with 50 mg placebo tablets once daily for 7 days, then 100mg placebo tablets once daily from day 8 to day 365, then taper with 50 mg placebo tablets once daily for 7 days, followed by 25 mg placebo tablets once daily for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 4 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. | Baseline and Week 4 | 
| Change From Baseline in the Average Daily Number of Moderate to Severe Hot Flushes at Week 12 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. | Baseline and Week 12 | 
| Change From Baseline in the Average Daily Severity of Hot Flushes at Week 4 | Severity ranged from mild (sensation of heat without sweating); moderate (sensation of heat with sweating; able to continue activity) to severe (sensation of heat with sweating; causing cessation of activity). The average daily severity of hot flushes for each time period was calculated as (1*Number of mild+2*Number of moderate+3*Number of severe)/(Total number of hot flushes). For the days with no hot flushes, the severity score was set as 0. As this was derived from the count data, there was no maximum; the minimum score was 0; the higher values showed worse outcomes. | Baseline and Week 4 | 
| Change From Baseline in the Average Daily Severity of Hot Flushes at Week 12 | Severity ranged from mild (sensation of heat without sweating); moderate (sensation of heat with sweating; able to continue activity) to severe (sensation of heat with sweating; causing cessation of activity). The average daily severity of hot flushes for each time period was calculated as (1*Number of mild+2*Number of moderate+3*Number of severe)/(Total number of hot flushes). For the days with no hot flushes, the severity score was set as 0. As this was derived from the count data, there was no maximum; the minimum score was 0; the higher values showed worse outcomes. | Baseline and Week 12 | 
| Number of Participants With All Adjudicated Ischemic Cardiovascular (CV) Events | Adjudicated ischemic cardiovascular events were a composite of: a) Coronary Heart Disease (CHD)-related death; b) New Myocardial Infarction (MI) (non-procedure-related MI); c) Documented new onset of unstable angina requiring hospitalization; d) Unscheduled coronary revascularization procedures (percutaneous coronary intervention) or bypass grafting. | Baseline up to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Minimal Clinically Meaningful Decrease in the Average Daily Number of Hot Flushes | A mean decrease from baseline of at least 5.35 moderate to severe hot flushes at week 12 in the participants was considered clinically meaningful. | Baseline and Week 12 | 
| Percentage of Participants With at Least 50% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. | Baseline, Week 4 and Week 12 | 
| Percentage of Participants With at Least 75% Reduction From Baseline in the Number of Moderate and Severe Hot Flushes | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. | Baseline, Week 4 and Week 12 | 
| Median Time to the First Day of 3 Consecutive Days of at Least 50% Reduction in Hot Flushes | Time to response was defined as the time-to-first 50% reduction in the average daily number of moderate to severe hot flushes over 3 consecutive days. | Week 12 | 
| Change From Baseline in Adjusted Means in the Number of Moderate and Severe Hot Flushes at Month 6 and Month 12 | The average daily number of moderate and severe hot flushes was calculated as the sum of the number of moderate and severe hot flushes on each day divided by the number of days with data. Moderate hot flushes: sensation of heat with sweating; able to continue activity; and severe hot flushes: sensation of heat with sweating; causing cessation of activity. Adjusted mean was calculated by using change from baseline as response variable, treatment as factor, and baseline as covariate using the observed cases. | Baseline, Month 6 and Month 12 | 
| Change From Baseline in Adjusted Means in the Hot Flush Severity Score at Month 6 and Month 12 | Severity: mild (heat sensation without sweating); moderate (heat sensation with sweating; able to continue activity); severe (heat sensation with sweating; causing cessation of activity). Average daily severity of hot flushes= (1*Number of mild+2*Number of moderate+3*Number of severe)/(Total number of hot flushes). Days with no hot flushes: severity score=0. As it was derived from count data, there was no maximum; minimum score=0; higher values= worse outcomes. Adjusted mean: calculated using change from baseline=response variable, treatment=factor and baseline=covariate using observed cases. | Baseline, Month 6 and Month 12 | 
| Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Week 12 | GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms [range 0-33], anxiety [range 0-18], depression [range 0-15], somatic symptoms [range 0-21], vasomotor symptoms [range 0-6], and sexual dysfunction [range 0-3]). A decrease in the total climacteric score indicated an improvement in symptoms. | Baseline and Week 12 | 
| Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 6 | GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms [range 0-33], anxiety [range 0-18], depression [range 0-15], somatic symptoms [range 0-21], vasomotor symptoms [range 0-6], and sexual dysfunction [range 0-3]). A decrease in the total climacteric score indicated an improvement in symptoms. | Baseline and Month 6 | 
| Change From Baseline in the Total Greene Climacteric Scale (GCS) Score and GCS Subscores at Month 12 | GCS: a 21 item evaluation of symptoms which asked participants how bothered they were with particular symptom at the moment. Each item was scored as 0 = Not at all, 1 = A little, 2 = Quite a bit, and 3 = Extremely. A total score was derived from the sum of the 21 items (range 0-63). GCS was also used to generate 6 individual scores (psychological symptoms [range 0-33], anxiety [range 0-18], depression [range 0-15], somatic symptoms [range 0-21], vasomotor symptoms [range 0-6], and sexual dysfunction [range 0-3]). A decrease in the total climacteric score indicated an improvement in symptoms. | Baseline and Month 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Week 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). | Week 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 6 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). | Month 6 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for Main Study Efficacy Population at Month 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). | Month 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Week 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). | Week 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 6 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). | Month 6 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Symptom Rating (PGI-R) for MITT Population of Efficacy Substudy at Month 12 | PGI-R scale was intended to assess the study participant's perception of symptoms. Participants were requested to identify the severity of their hot flush symptoms. It was a 5-scale which ranged from 1 (None) to 5 (Severe). | Month 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Week 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). | Week 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 6 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). | Month 6 | 
| Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for Main Study Efficacy Population at Month 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). | Month 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Week 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). | Week 12 | 
| Percentage of Participants With Categorical Scores on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 6 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). | Month 6 | 
| Percentage of Participants With Categorical Scores Based on Patient Global Impression Change (PGI-C) for MITT Population of Efficacy Substudy at Month 12 | PGI-C score was intended to assess the study participant's perception of changes in hot flushes. It was 7-point scale which ranged from 1 (Very Much Improved) to 7 (Very Much Worse). | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menopause, Hot Flush, Hot Flash, Desvenlafaxine succinate Sustained Release