Trial Outcomes & Findings for Interdisciplinary Study of Two Novel Anticonvulsants in Alcoholism (NCT NCT00862563)

Last Updated: 2015-04-28

Results Overview

Mean standard drinks consumed per day for each treatment week, weeks 10 thru 12. Actual mean values obtained are shown. Analyses are based on model generated least squares means for a two -way repeated measures mixed models analysis for data obtained for weeks 1 through 12, with baseline values used as covariates. Week (time) was used as the within subject factor and treatment group was the between group factor.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

85 participants

Primary outcome timeframe

Weeks 10, 11, 12

Results posted on

2015-04-28

Participant Flow

Participant milestones

Participant milestones
Measure	Zonisamide zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Levetiracetam Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.	Topiramate Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Sugar Pill Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.
Overall Study STARTED	19	21	21	24
Overall Study COMPLETED	15	17	15	19
Overall Study NOT COMPLETED	4	4	6	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Interdisciplinary Study of Two Novel Anticonvulsants in Alcoholism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide n=19 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Levetiracetam n=21 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.	Topiramate n=21 Participants topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Sugar Pill n=24 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Total n=85 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=157 Participants	0 Participants n=390 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=99 Participants	21 Participants n=107 Participants	21 Participants n=206 Participants	24 Participants n=157 Participants	85 Participants n=390 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=157 Participants	0 Participants n=390 Participants
Age, Continuous	47.0 Years STANDARD_DEVIATION 10.0 • n=99 Participants	47.5 Years STANDARD_DEVIATION 10.5 • n=107 Participants	46.8 Years STANDARD_DEVIATION 10.5 • n=206 Participants	46.8 Years STANDARD_DEVIATION 7.3 • n=157 Participants	47.0 Years STANDARD_DEVIATION 9.4 • n=390 Participants
Sex: Female, Male Female	8 Participants n=99 Participants	9 Participants n=107 Participants	9 Participants n=206 Participants	11 Participants n=157 Participants	37 Participants n=390 Participants
Sex: Female, Male Male	11 Participants n=99 Participants	12 Participants n=107 Participants	12 Participants n=206 Participants	13 Participants n=157 Participants	48 Participants n=390 Participants
Region of Enrollment United States	19 participants n=99 Participants	21 participants n=107 Participants	21 participants n=206 Participants	24 participants n=157 Participants	85 participants n=390 Participants
Education	15.6 years STANDARD_DEVIATION 2.5 • n=99 Participants	15.2 years STANDARD_DEVIATION 2.4 • n=107 Participants	15.4 years STANDARD_DEVIATION 1.9 • n=206 Participants	15.3 years STANDARD_DEVIATION 2.7 • n=157 Participants	15.4 years STANDARD_DEVIATION 2.4 • n=390 Participants
Alcohol Use Identification Test (AUDIT)	22.1 units on a scale STANDARD_DEVIATION 5.9 • n=99 Participants	23.1 units on a scale STANDARD_DEVIATION 5.2 • n=107 Participants	24.6 units on a scale STANDARD_DEVIATION 5.7 • n=206 Participants	23.7 units on a scale STANDARD_DEVIATION 4.7 • n=157 Participants	23.4 units on a scale STANDARD_DEVIATION 5.4 • n=390 Participants
Wechsler Abbreviated Scale of Intelligence (WAIS)	115.3 scale scores STANDARD_DEVIATION 8.9 • n=99 Participants	113.3 scale scores STANDARD_DEVIATION 11.6 • n=107 Participants	113.6 scale scores STANDARD_DEVIATION 12.6 • n=206 Participants	110.7 scale scores STANDARD_DEVIATION 14.0 • n=157 Participants	113.1 scale scores STANDARD_DEVIATION 12.0 • n=390 Participants

PRIMARY outcome

Timeframe: Weeks 10, 11, 12

Population: Alcohol dependent subjects. Number of participants analyzed are provided for the number of subjects for data that was available for the timeframe for the specific analyses, i.e. Weeks 10,11,12.

Outcome measures

Outcome measures
Measure	Zonisamide n=16 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=20 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=16 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=17 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
The Primary Efficacy Measure is the Mean Number of Drinks Consumed Per Day Over the Period From Treatment Weeks 10 Through 12 When All Study Medications Should be at Their Maximum Steady Levels Based on Their Known Pharmacokinetic Properties. Week 10	3.8 Standard Drinks per day Standard Error 0.9	6.3 Standard Drinks per day Standard Error 0.9	3.2 Standard Drinks per day Standard Error 0.8	4.6 Standard Drinks per day Standard Error 0.8
The Primary Efficacy Measure is the Mean Number of Drinks Consumed Per Day Over the Period From Treatment Weeks 10 Through 12 When All Study Medications Should be at Their Maximum Steady Levels Based on Their Known Pharmacokinetic Properties. Week 11	3.4 Standard Drinks per day Standard Error 0.6	6.8 Standard Drinks per day Standard Error 1.2	2.7 Standard Drinks per day Standard Error 0.7	4.3 Standard Drinks per day Standard Error 0.7
The Primary Efficacy Measure is the Mean Number of Drinks Consumed Per Day Over the Period From Treatment Weeks 10 Through 12 When All Study Medications Should be at Their Maximum Steady Levels Based on Their Known Pharmacokinetic Properties. Week 12	2.5 Standard Drinks per day Standard Error 0.7	6.0 Standard Drinks per day Standard Error 0.9	2.5 Standard Drinks per day Standard Error 0.7	4.3 Standard Drinks per day Standard Error 0.7

SECONDARY outcome

Timeframe: Week 12

Population: Alcohol dependent subjects.

Total Scores AB-Neurotoxicity Scale Week 12. This scale provides subject ratings of anticonvulsant neurotoxic effects. Scores may range 0 to 72, with possibility of an additional 30 points being for complaints not listed in the list of complaints provides. Total scores, therefore, may be as high as 102, with higher scores indicating greater severity of problems. Actual mean scores are shown. Means for the analysis are least means squares values obtained from a two-way repeated measures mixed models analysis, with Week (time) as the the within subject factor and treatment as the between group factor. Baseline values were used as covariates.

Outcome measures

Outcome measures
Measure	Zonisamide n=15 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=17 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=15 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=19 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
AB-Neurotoxicity Scale.	7.1 Scale Scores Standard Error 2.2	11.3 Scale Scores Standard Error 2.7	15.4 Scale Scores Standard Error 3.3	5.8 Scale Scores Standard Error 1.6

SECONDARY outcome

Timeframe: Weeks 10, 11, 12

Population: Alcohol dependent subjects. Alcohol dependent subjects. Number of participants analyzed are provided for the number of subjects for data that was available for the time frame for the specific analyses, i.e. Weeks 10,11,12.

Mean weekly values for each treatment group for percent days heavy drinking. Heavy drinking was defined as 4 or more drinks per day for women and 5 or more drinks per day for men.

Outcome measures

Outcome measures
Measure	Zonisamide n=16 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=20 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=16 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=17 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
Mean Percent Days Heavy Drinking Week 10	38.4 Percentage of Days/Week Standard Error 10.7	65.7 Percentage of Days/Week Standard Error 6.5	32.1 Percentage of Days/Week Standard Error 8.5	49.6 Percentage of Days/Week Standard Error 9.4
Mean Percent Days Heavy Drinking Week 11	36.6 Percentage of Days/Week Standard Error 8.5	61.7 Percentage of Days/Week Standard Error 8.1	29.5 Percentage of Days/Week Standard Error 7.1	47.9 Percentage of Days/Week Standard Error 9.3
Mean Percent Days Heavy Drinking Week 12	34.3 Percentage of Days/Week Standard Error 11.0	60.9 Percentage of Days/Week Standard Error 8.0	21.0 Percentage of Days/Week Standard Error 8.1	44.5 Percentage of Days/Week Standard Error 8.7

SECONDARY outcome

Timeframe: Weeks 10, 11, 12

Population: Alcohol dependent subjects. Alcohol dependent subjects. Number of participants analyzed are provided for the number of subjects for data that was available for the timeframe for the specific analyses, i.e. Weeks 10,11,12.

Mean percent days drinking for Weeks 10, 11, 12. A drinking day is considered to be a day in which 1 or more drinks have been consumed. Means are model generated least means squares values obtained from a two-way repeated measures analysis from data obtained from Weeks 1 through 12, with Week as the within subject factor and treatment group as the between group factor.

Outcome measures

Outcome measures
Measure	Zonisamide n=15 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=17 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=15 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=19 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
Percent Days Drinking Week 10	61.6 Percentage of Days/ Week Standard Error 9.5	72.2 Percentage of Days/ Week Standard Error 8.3	51.8 Percentage of Days/ Week Standard Error 10.1	83.6 Percentage of Days/ Week Standard Error 5.2
Percent Days Drinking Week 11	62.1 Percentage of Days/ Week Standard Error 9.3	68.9 Percentage of Days/ Week Standard Error 8.6	43.8 Percentage of Days/ Week Standard Error 9.6	87.2 Percentage of Days/ Week Standard Error 5.1
Percent Days Drinking Week 12	61.3 Percentage of Days/ Week Standard Error 9.9	73.1 Percentage of Days/ Week Standard Error 7.6	51.4 Percentage of Days/ Week Standard Error 11.0	78.2 Percentage of Days/ Week Standard Error 6.2

SECONDARY outcome

Timeframe: Baseline & Week 12

Population: Alcohol Dependent Subjects. Number of participants analyzed represent the number for whom Week 12 data was available.

Number of words generated that start with a set of 3 letters. The COWAT provides a measure of verbal fluency. Actual means for COWAT results are shown.

Outcome measures

Outcome measures
Measure	Zonisamide n=13 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=17 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=15 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=17 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
Controlled Word Association Test (COWAT)- Letter Fluency Baseline	46.5 Number of Words Produced Standard Error 3.1	46.2 Number of Words Produced Standard Error 3.0	43.4 Number of Words Produced Standard Error 3.8	47.4 Number of Words Produced Standard Error 2.8
Controlled Word Association Test (COWAT)- Letter Fluency Week 12	32.5 Number of Words Produced Standard Error 2.2	45.4 Number of Words Produced Standard Error 2.7	28.1 Number of Words Produced Standard Error 2.0	50.5 Number of Words Produced Standard Error 2.4

SECONDARY outcome

Timeframe: Baseline, Week12

Population: Alcohol Dependent Subjects. Number of participants analyzed represent the number for whom Week 12 data was available.

Number of words produced by subjects over 60 seconds for a semantic category (Animals). The COAWAT-Category sub-test provides a measure of verbal fluency. Mean value shown are actual means for the number of words produced.

Outcome measures

Outcome measures
Measure	Zonisamide n=13 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=17 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=15 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=17 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
COWAT-Category Baseline	22.6 Number of Words Produced Standard Error 1.1	20.9 Number of Words Produced Standard Error 0.9	21.9 Number of Words Produced Standard Error 1.3	21.6 Number of Words Produced Standard Error 1.2
COWAT-Category Week 12	17.4 Number of Words Produced Standard Error 0.7	21.2 Number of Words Produced Standard Error 1.0	17.0 Number of Words Produced Standard Error 1.2	20.8 Number of Words Produced Standard Error 0.7

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Alcohol Dependent Subjects. Number of participants analyzed represent the number for whom Week 12 data was available.

WMS Digit Span is a measure of working memory. Subjects respond by repeating lists of number sequences presented by the test administrator. Age adjusted scores are presented below. Scores may range between 1 and 19, with lower scores indicating poorer performance on the task.

Outcome measures

Outcome measures
Measure	Zonisamide n=13 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=17 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=15 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=17 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
Wechsler Memory Scales (WMS)-3d Ed Digit Span-Age Adjusted Total Baseline	11.8 units on a scale Standard Error 0.8	11.9 units on a scale Standard Error 0.7	12.1 units on a scale Standard Error 0.6	12.6 units on a scale Standard Error 0.7
Wechsler Memory Scales (WMS)-3d Ed Digit Span-Age Adjusted Total Week 12	10.0 units on a scale Standard Error 0.9	12.2 units on a scale Standard Error 0.8	7.7 units on a scale Standard Error 0.6	13.0 units on a scale Standard Error 0.9

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Alcohol Dependent Subjects. Number of participants analyzed represent the number for whom Week 12 data was available.

WMS Spatial Span test measures working memory for a spatial sequence of numbers. This assesses visual working memory. Age adjusted scaled scores are presented. Score may range between 1 and 19, with lower scores indicating greater impairment in performance.

Outcome measures

Outcome measures
Measure	Zonisamide n=13 Participants zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Sugar Pill n=17 Participants Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.	Topiramate n=15 Participants Topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Levetiracetam n=17 Participants Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.
Wechsler Memory Scale-3rd Ed. Spatial Span Baseline	10.8 units on a scale Standard Error 0.7	10.5 units on a scale Standard Error 0.6	12.0 units on a scale Standard Error 0.6	10.8 units on a scale Standard Error 0.8
Wechsler Memory Scale-3rd Ed. Spatial Span Week 12	7.9 units on a scale Standard Error 0.9	10.9 units on a scale Standard Error 0.5	8.4 units on a scale Standard Error 0.7	10.4 units on a scale Standard Error 0.8

Adverse Events

Zonisamide

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Levetiracetam

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Topiramate

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zonisamide n=19 participants at risk zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Levetiracetam n=21 participants at risk Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.	Topiramate n=21 participants at risk topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Sugar Pill n=24 participants at risk Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.
Psychiatric disorders Suicide Attempt	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.

Other adverse events

Additional Information

Dr. Domenic A Ciraulo, Professor

Department of Psychiatry, Boston Univ School of Medicine

Phone: 617-414-1990

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Zonisamide n=19 participants at risk zonisamide: Zonisamide will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 400 mg of zonisamide.	Levetiracetam n=21 participants at risk Levetiracetam: Levetiracetam will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses of 2000 mg levetiracetam capsules.	Topiramate n=21 participants at risk topiramate: Topiramate will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14. Subjects will be dose titrated as tolerated to a target doses 300 mg topiramate.	Sugar Pill n=24 participants at risk Placebo: Matched placebo will be administered orally twice daily beginning on Day 1, Week 1 and continue through Day 7, Week 14.
Psychiatric disorders Anxiety	15.8% 3/19 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	14.3% 3/21 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	8.3% 2/24 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
General disorders Altered Taste	10.5% 2/19 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Confusion	0.00% 0/19 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Gastrointestinal disorders Constipation	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Decreased Libido	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.2% 1/24 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Psychiatric disorders Depression	0.00% 0/19 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	14.3% 3/21 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Gastrointestinal disorders Diarrhea	10.5% 2/19 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	8.3% 2/24 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Psychiatric disorders Dissociation	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Psychiatric disorders Disoriented	0.00% 0/19 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Reproductive system and breast disorders Erectile Dsyfunction	0.00% 0/19 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	14.3% 3/21 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Fatigue	15.8% 3/19 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	23.8% 5/21 • Number of events 5 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	12.5% 3/24 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Gastrointestinal disorders GI Distress	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Headache	15.8% 3/19 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	28.6% 6/21 • Number of events 6 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	19.0% 4/21 • Number of events 4 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	8.3% 2/24 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Impaired Concentration	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.2% 1/24 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Impaired Memory	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	14.3% 3/21 • Number of events 3 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.2% 1/24 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Psychiatric disorders Insomnia	10.5% 2/19 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Irritability	10.5% 2/19 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	19.0% 4/21 • Number of events 4 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Lightheaded	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Loss of Appetite	10.5% 2/19 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Gastrointestinal disorders Nausea	0.00% 0/19 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	8.3% 2/24 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Paraesthesia	0.00% 0/19 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	19.0% 4/21 • Number of events 4 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	8.3% 2/24 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Skin and subcutaneous tissue disorders Prurtitus	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Skin and subcutaneous tissue disorders Rash	10.5% 2/19 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Sedation	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Infections and infestations Sinus Infection	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Slowed Thinking	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Weight Loss	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	9.5% 2/21 • Number of events 2 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.
Nervous system disorders Word Finding	5.3% 1/19 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/21 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	4.8% 1/21 • Number of events 1 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.	0.00% 0/24 • Adverse event data was collected for a period of 17 weeks for each subject and for a total of throughout the entire study.