Vilazodone for Menopausal Hot Flashes

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01680900
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 36
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

This is a pilot study to determine proof in principle that vilazodone, a selective serotonin reuptake inhibitor and 5HT1a agonist, reduces the frequency and severity of menopausal hot flashes relative to placebo. A secondary aim is to evaluate improvement in menopause-related quality of life.

Condition or Disease	Intervention/Treatment	Phase
Hot Flushes	Drug: vilazodone; Drug: placebo capsules	N/A

Detailed Description

This is a proposal to conduct a small clinical trial for proof in principle that vilazodone reduces the frequency and severity of menopausal hot flashes. An additional exploratory aim is to identify improvement in menopause-related quality of life. Healthy, perimenopausal women ages 45-60 with an average of 4 or more moderate or severe hot flashes/night sweats per day for 3 screening weeks will be randomized to 8 weeks of treatment in a 2:1 ratio of vilazodone or matching placebo pills. Flexible dosing of vilazodone will start at 10 mg once/day for 7 days, increase to 20 mg/day for 1 more week and increase to 40 mg once/day at week 3 if unimproved. The primary outcome assessments are the frequency and severity of hot flashes at week 4 and week 8 as assessed by prospective daily diaries (using 7-day mean scores from the daily diaries). The secondary outcome is clinical improvement, defined as hot flash frequency >=50% decrease from baseline. Treatment-emergent adverse events will be monitored and patient ratings of tolerability will be obtained.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vilazodone for Menopausal Hot Flashes: A Proof in Principle Study
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: experimental 1 vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks	Drug: vilazodone; capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.; Other Names: viibryd
Placebo Comparator: placebo capsules (sugar pill) Placebo capsules matched to the drug dose for 8 weeks	Drug: placebo capsules; placebo capsules matched to drug capsules.

Outcome Measures

Primary Outcome Measures

1. Daily Diary Ratings of Frequency of Hot Flashes [Week 8.]

   Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported.

2. Daily Diary Ratings of Severity of Hot Flashes [Week 8.]

   Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe).

Secondary Outcome Measures

1. Percent of Patients With >=50% Reduction in Moderate to Severe Hot Flashes [Percent change from baseline at Week 8]

   Percent of patients with n >=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries

2. Menopause-related Quality of Life (MENQOL) [Week 8]

   The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic.

Other Outcome Measures

1. Number of Participants With Adverse Events [Baseline and Week 12]

   A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8.

2. Percentage of Participants That Were Satisfied or Very Satisfied [Week 8]

   Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied).

3. Sheehan Global Ratings of Symptom (Hot Flash)Interference [Change from Baseline at Week 8]

   Global ratings on a 10-point scale of the degree that symptoms interfere overall, with work, social activities and family life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 60 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women ages 45-60 years

• Amenorrhea for 60 days or more or postmenopausal or bi-lateral oophorectomy.

• 4 or more moderate or severe hot flashes or night sweats per 24 hour period (28/week) as recorded on daily diaries in 3 screening weeks.

• Hot flashes/night sweats rated as moderate to severe and/or bothersome (moderately to a lot) on 4 or more days/nights in each screen week.

• In general good health.

• Signed informed consent.

Exclusion Criteria:

• Psychotropic medications currently or within the last 30 days.

• Current use of hormonal medications such as hormone therapy or hormonal contraception or any treatment for hot flashes (Prescription, over-the-counter or herbal).

• Drug or alcohol abuse in the past year.

• Lifetime diagnosis of psychosis or bipolar disorder.

• Suicide attempt in the past 3 years or any current suicidal ideation.

• Current major depression.

• Not using a medically approved, non-hormonal method of birth control if sexually active and not postmenopausal (12 or more months since last menstrual period or bi-lateral oophorectomy).

• Pregnancy, intending pregnancy or breast feeding.

• Any severe of unstable medical illness, e.g., breast or ovarian cancer, seizure disorders, etc.

• Current participation in another intervention study.

• Inability or unwillingness to complete study procedures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dept OB/GYN, Mudd Professorship Suite	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Forest Laboratories

Investigators

• Principal Investigator: Ellen W Freeman, PhD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ellen Freeman, Research Profesor, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01680900
• Other Study ID Numbers: 816164
• First Posted: Sep 7, 2012
• Last Update Posted: Jan 14, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by Ellen Freeman, Research Profesor, University of Pennsylvania: menopause; hot flashes; vilazodone
• Additional relevant MeSH terms: Hot Flashes; Vilazodone Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
Period Title: Overall Study
STARTED	24	12
COMPLETED	20	11
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)	Total
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.	Total of all reporting groups
Overall Participants	24	12	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.5 (3.7)	52.7 (4.2)	51.9 (3.9)
Sex: Female, Male (Count of Participants)
Female	24 100%	12 100%	36 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	24 100%	12 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Daily Diary Ratings of Frequency of Hot Flashes
Description	Hot flash frequency and severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported.
Time Frame	Week 8.

Outcome Measure Data

Analysis Population Description

all participants randomized to treatment

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
Measure Participants	24	12
Mean (95% Confidence Interval) [number of hot flashes]	3.65	4.71

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental 1, Placebo Capsules (Sugar Pill)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.06
	Confidence Interval	(2-Sided) 95%; -2.60 to -0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent of Patients With >=50% Reduction in Moderate to Severe Hot Flashes
Description	Percent of patients with n >=50% reduction in frequency of moderate to severe hot flashes calculated from daily diaries
Time Frame	Percent change from baseline at Week 8

Outcome Measure Data

Analysis Population Description

all participants with at least one treatment response

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
Measure Participants	24	12
Number [percentage of participants]	65 270.8%	83 691.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental 1, Placebo Capsules (Sugar Pill)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Menopause-related Quality of Life (MENQOL)
Description	The MENQOL is a validated measure to assess the presence and bother of menopausal symptoms. This will be exploratory. Each of 29 items is rated on a scale of 0 to 6 (extremely bothersome). The items are divided into 4 subscales. The item scores are summed in each subscale and means are computed for the 4 subscales. The total score is the sum of the mean subscale scores. Higher scores are more symptomatic.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
Measure Participants	24	12
Mean (95% Confidence Interval) [units on a scale]	1.89	2.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental 1, Placebo Capsules (Sugar Pill)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.75 to -0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Other Pre-specified Outcome

Title	Number of Participants With Adverse Events
Description	A 17 item checklist of general adverse and withdrawal symptoms. It will be used at baseline and Week 12. Adverse events will be obtained by subject report at Week 4 and Week 8.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
Measure Participants	24	12
Number [participants]	17 70.8%	6 50%

5. Other Pre-specified Outcome

Title	Percentage of Participants That Were Satisfied or Very Satisfied
Description	Patient global rating of satisfaction with medication reported on a scale of 0 to 5 (very satisfied).
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

all participants with at least one treatment response.

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
Measure Participants	24	12
Number [percentage of participants]	65 270.8%	75 625%

6. Other Pre-specified Outcome

Title	Sheehan Global Ratings of Symptom (Hot Flash)Interference
Description	Global ratings on a 10-point scale of the degree that symptoms interfere overall, with work, social activities and family life.
Time Frame	Change from Baseline at Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Primary Outcome

Title	Daily Diary Ratings of Severity of Hot Flashes
Description	Hot flash severity will be recorded daily in the am and pm on a scale of 0 (none) to 3 (severe). The frequency of hot flashes was the number reported. The severity of hot flashes was rated on a scale of 0 (none) to 3 (severe). 7-day averages were calculated for baseline, week 4 and week 8 and a mean daily score was obtained for analysis. Baseline values were the means of the first 2 screen weeks. Possible range of the severity scale for the daily mean was 0 (none) to 3 (severe).
Time Frame	Week 8.

Outcome Measure Data

Analysis Population Description

all participants randomized to treatment

Arm/Group Title	Experimental 1	Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.	Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
Measure Participants	24	12
Mean (95% Confidence Interval) [units on a scale]	1.17	1.39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental 1, Placebo Capsules (Sugar Pill)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.74 to -0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Experimental 1		Placebo Capsules (Sugar Pill)
Arm/Group Description	vilazodone (viibryd). 20 mg or 40 mg/day for 8 weeks vilazodone: capsules once/day for 8 weeks. Dose starts at 10 mg for 7 days, increases to 20 mg/day for 7 days, increases to 40 mg/day at week 3 of unimproved.		Placebo capsules matched to the drug dose for 8 weeks placebo capsules: placebo capsules matched to drug capsules.
All Cause Mortality
	Experimental 1		Placebo Capsules (Sugar Pill)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Experimental 1		Placebo Capsules (Sugar Pill)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Experimental 1		Placebo Capsules (Sugar Pill)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/24 (70.8%)		6/12 (50%)
Gastrointestinal disorders
diarrhea	9/24 (37.5%)		0/12 (0%)
nausea	7/24 (29.2%)		0/12 (0%)
dehydration	1/24 (4.2%)		3/12 (25%)
Nervous system disorders
headache	4/24 (16.7%)		2/12 (16.7%)
dry mouth	4/24 (16.7%)		3/12 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.