Trial Outcomes & Findings for Effectiveness of Zonisamide in Alcohol Dependent Veterans (NCT NCT02368431)
NCT ID: NCT02368431
Last Updated: 2020-12-07
Results Overview
Difference between groups in the number of total standard drinks per week over 8 weeks (weeks 9-16, the weeks on the target dose) performed using a mixed models longitudinal analysis.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
92 participants
Primary outcome timeframe
over 8 weeks (weeks 9-16)
Results posted on
2020-12-07
Participant Flow
Randomization was conducted by the pharmacy using a 1:1 randomization in blocks of 4 and stratified by site.
Participant milestones
| Measure |
Zonisamide
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
46
|
|
Overall Study
COMPLETED
|
22
|
27
|
|
Overall Study
NOT COMPLETED
|
24
|
19
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
All available data was utilized in the analysis using mixed models
Baseline characteristics by cohort
| Measure |
Zonisamide
n=43 Participants
Men or women veterans, ages 21-70, met Diagnostic and Statistical Manual IV Text Revision (DSM-IV) criteria for current Alcohol Dependence (AD) (determined by structured clinical interview)
|
Placebo
n=45 Participants
Men or women veterans, ages 21-70, met Diagnostic and Statistical Manual IV Text Revision (DSM-IV) criteria for current Alcohol Dependence (AD) (determined by structured clinical interview)
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49.1 years
STANDARD_DEVIATION 11.7 • n=43 Participants
|
51.8 years
STANDARD_DEVIATION 10.8 • n=45 Participants
|
50.5 years
STANDARD_DEVIATION 11.3 • n=88 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=42 Participants • All available data was utilized in the analysis using mixed models
|
2 Participants
n=44 Participants • All available data was utilized in the analysis using mixed models
|
5 Participants
n=86 Participants • All available data was utilized in the analysis using mixed models
|
|
Sex: Female, Male
Male
|
39 Participants
n=42 Participants • All available data was utilized in the analysis using mixed models
|
42 Participants
n=44 Participants • All available data was utilized in the analysis using mixed models
|
81 Participants
n=86 Participants • All available data was utilized in the analysis using mixed models
|
|
Race/Ethnicity, Customized
Caucasian
|
31 Participants
n=43 Participants
|
31 Participants
n=45 Participants
|
62 Participants
n=88 Participants
|
|
Race/Ethnicity, Customized
African American
|
11 Participants
n=43 Participants
|
11 Participants
n=45 Participants
|
22 Participants
n=88 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=43 Participants
|
4 Participants
n=45 Participants
|
5 Participants
n=88 Participants
|
PRIMARY outcome
Timeframe: over 8 weeks (weeks 9-16)Population: All available data was utilized in the analysis using mixed models
Difference between groups in the number of total standard drinks per week over 8 weeks (weeks 9-16, the weeks on the target dose) performed using a mixed models longitudinal analysis.
Outcome measures
| Measure |
Zonisamide
n=43 Participants
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 Participants
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Number of Drinks Per Week
Week 9
|
17.8 Number of total drinks
Standard Error 7.6
|
8.1 Number of total drinks
Standard Error 7.5
|
|
Number of Drinks Per Week
Week 10
|
12.2 Number of total drinks
Standard Error 4.6
|
8.8 Number of total drinks
Standard Error 4.5
|
|
Number of Drinks Per Week
Week 11
|
15.9 Number of total drinks
Standard Error 5.6
|
3.6 Number of total drinks
Standard Error 5.5
|
|
Number of Drinks Per Week
Week 12
|
10.3 Number of total drinks
Standard Error 3.6
|
6.2 Number of total drinks
Standard Error 3.6
|
|
Number of Drinks Per Week
Week 13
|
9.4 Number of total drinks
Standard Error 6.9
|
12.5 Number of total drinks
Standard Error 6.3
|
|
Number of Drinks Per Week
Week 14
|
9.9 Number of total drinks
Standard Error 3.4
|
4.3 Number of total drinks
Standard Error 3.1
|
|
Number of Drinks Per Week
Week 15
|
13.7 Number of total drinks
Standard Error 4.1
|
3.3 Number of total drinks
Standard Error 3.7
|
|
Number of Drinks Per Week
Week 16
|
11.1 Number of total drinks
Standard Error 5.1
|
8.7 Number of total drinks
Standard Error 4.3
|
SECONDARY outcome
Timeframe: BaselinePopulation: All available data was utilized in the analysis using mixed models
Percentage of Subjects with No Heavy Drinking Days (PSNHDD) The PSNHDD can be derived from each subject's timeline follow back (TLFB) data.
Outcome measures
| Measure |
Zonisamide
n=43 Participants
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 Participants
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Percentage of Subjects With No Heavy Drinking Days (PSNHDD)
Participants with No Heavy Drinking Days
|
16 Participants
|
28 Participants
|
|
Percentage of Subjects With No Heavy Drinking Days (PSNHDD)
Participants with Heavy Drinking Day
|
27 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 4, 8 and 16Population: All available data was utilized in the analysis using mixed models
Difference between groups on change in levels of Gamma glutamyl transferase (GGT) over time from baseline to endpoint, which will include several interim data points. This will analyzed with a mixed models longitudinal analysis (repeated measures). Normal range for GGT levels are 10 U/L - 65 U/L - above 65 U/L above 65 U/L is considered a high GGT level
Outcome measures
| Measure |
Zonisamide
n=43 Participants
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 Participants
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Gamma Glutamyl Transferase (GGT)
Baseline
|
76.0 Units/Liter (U/L)
Standard Error 12.7
|
78.2 Units/Liter (U/L)
Standard Error 12.2
|
|
Gamma Glutamyl Transferase (GGT)
Week 4
|
63.4 Units/Liter (U/L)
Standard Error 8.8
|
50.0 Units/Liter (U/L)
Standard Error 8.7
|
|
Gamma Glutamyl Transferase (GGT)
Week 8
|
61.40 Units/Liter (U/L)
Standard Error 8.8
|
45.5 Units/Liter (U/L)
Standard Error 8.7
|
|
Gamma Glutamyl Transferase (GGT)
Week 16
|
62.8 Units/Liter (U/L)
Standard Error 10.2
|
46.4 Units/Liter (U/L)
Standard Error 9.9
|
SECONDARY outcome
Timeframe: over 16 weeks (weeks 1-16)Population: All available data was utilized in the analysis using mixed models
The difference in the number of heavy drinking days per week compared between groups (zonisamide and placebo) during the time spent on the target dose of the medication. Performed using a mixed models longitudinal analysis (repeated measures).
Outcome measures
| Measure |
Zonisamide
n=43 Participants
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 Participants
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Number of Heavy Drinking Days Per Week
Week 1
|
1.1 Number of heavy drinking days
Standard Error 0.3
|
0.6 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 2
|
0.9 Number of heavy drinking days
Standard Error 0.3
|
0.9 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 3
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 4
|
1.1 Number of heavy drinking days
Standard Error 0.3
|
0.3 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 5
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
0.5 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 6
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
0.6 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 7
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
0.6 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Weel 8
|
1.0 Number of heavy drinking days
Standard Error 0.3
|
0.5 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 9
|
1.0 Number of heavy drinking days
Standard Error 0.3
|
0.5 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 10
|
1.0 Number of heavy drinking days
Standard Error 0.3
|
0.5 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 11
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
0.4 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 12
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
0.5 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 13
|
0.7 Number of heavy drinking days
Standard Error 0.3
|
0.3 Number of heavy drinking days
Standard Error 0.2
|
|
Number of Heavy Drinking Days Per Week
Week 14
|
0.9 Number of heavy drinking days
Standard Error 0.3
|
0.2 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 15
|
0.8 Number of heavy drinking days
Standard Error 0.3
|
0.5 Number of heavy drinking days
Standard Error 0.3
|
|
Number of Heavy Drinking Days Per Week
Week 16
|
11.4 Number of heavy drinking days
Standard Error 3.1
|
6.5 Number of heavy drinking days
Standard Error 3.0
|
SECONDARY outcome
Timeframe: over 16 weeks (weeks 1-16)Population: All available data was utilized in the analysis using mixed models
This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures. The AUQ is a 8 item participant rated questionnaire. Participants indicate how much they agree or disagree with the statements by selecting one number, 1 strongly disagree through 7 strongly agree. Participants can scores between 8 (lowest) - 56 (highest), the higher the score the more urge to drink.
Outcome measures
| Measure |
Zonisamide
n=43 Participants
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 Participants
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Alcohol Urge Questionnaire Score (AUQ)
Baseline
|
17.1 units on a scale
Standard Error 1.2
|
14.8 units on a scale
Standard Error 1.2
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 1
|
13.3 units on a scale
Standard Error 1.1
|
12.7 units on a scale
Standard Error 1.0
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 2
|
14.0 units on a scale
Standard Error 1.2
|
11.8 units on a scale
Standard Error 1.2
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 3
|
14.7 units on a scale
Standard Error 1.1
|
10.7 units on a scale
Standard Error 1.1
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 4
|
13.5 units on a scale
Standard Error 1.0
|
10.7 units on a scale
Standard Error 1.0
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 5
|
13.6 units on a scale
Standard Error 1.1
|
10.7 units on a scale
Standard Error 1.1
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 6
|
12.3 units on a scale
Standard Error 1.2
|
10.7 units on a scale
Standard Error 1.2
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 7
|
12.7 units on a scale
Standard Error 1.1
|
12.1 units on a scale
Standard Error 1.1
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 8
|
12.4 units on a scale
Standard Error 1.1
|
11.3 units on a scale
Standard Error 1.1
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 9
|
13.4 units on a scale
Standard Error 1.2
|
11.0 units on a scale
Standard Error 1.2
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 10
|
11.9 units on a scale
Standard Error 1.0
|
10.7 units on a scale
Standard Error 0.9
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 11
|
10.9 units on a scale
Standard Error 0.8
|
10.9 units on a scale
Standard Error 0.8
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 12
|
11.7 units on a scale
Standard Error 1.0
|
10.3 units on a scale
Standard Error 0.9
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 13
|
10.3 units on a scale
Standard Error 0.8
|
10.3 units on a scale
Standard Error 0.8
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 14
|
11.8 units on a scale
Standard Error 1.2
|
9.8 units on a scale
Standard Error 1.2
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 15
|
10.8 units on a scale
Standard Error 0.8
|
9.7 units on a scale
Standard Error 0.8
|
|
Alcohol Urge Questionnaire Score (AUQ)
Week 16
|
12.0 units on a scale
Standard Error 1.0
|
9.8 units on a scale
Standard Error 1.0
|
SECONDARY outcome
Timeframe: Over 16 weeks (Baseline and 16 weeks)Population: All available data was utilized in the analysis using mixed models
Change in quality of life scores measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). The Q-LES-Q is a 16 item participant rated questionnaire. Participants indicate how they are feeling over the 16 item from Very poor (1), Poor (2), Fair (3), Good (4), and Very Good (5). Participants can scores between 14 (lowest) - 70 (highest) the higher the score more satisfied with quality of life.
Outcome measures
| Measure |
Zonisamide
n=43 Participants
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 Participants
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Change in Quality of Life
Baseline
|
56.9 units on a scale
Standard Error 2.7
|
55.8 units on a scale
Standard Error 2.6
|
|
Change in Quality of Life
Week 16
|
73.3 units on a scale
Standard Error 3.5
|
72.9 units on a scale
Standard Error 3.1
|
SECONDARY outcome
Timeframe: over 16 weeks (Baseline and Week 16)Population: All available data was utilized in the analysis using mixed models
Change in level of alcohol-related problems measured by the Short Index of Problems (SIP). The SIP is a 15 item participant rated questionnaire. Participants rate the number of events that drinkers sometimes experience. Participants indicate how often each of the items has happened. They are scored by selecting one number, 0 Never; 1 Once or a few times; 2 Once or twice a week; 3 Daily or almost daily. Participants can scores between 0 (lowest) - 45 (highest) - the higher score the more drinking problems.
Outcome measures
| Measure |
Zonisamide
n=43 Participants
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 Participants
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Level of Alcohol-related Problems (SIP)
Baseline
|
4.8 units on a scale
Standard Error 0.4
|
5.3 units on a scale
Standard Error 0.4
|
|
Level of Alcohol-related Problems (SIP)
Week 16
|
1.2 units on a scale
Standard Error 0.5
|
1.9 units on a scale
Standard Error 0.5
|
Adverse Events
Zonisamide
Serious events: 4 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zonisamide
n=46 participants at risk
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 participants at risk
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Psychiatric disorders
Suicidal Ideation
|
6.5%
3/46 • Number of events 3 • 16 weeks
Adverse events were collected with a questionnaire of side effects at appointments over the 16 week period.
|
0.00%
0/46 • 16 weeks
Adverse events were collected with a questionnaire of side effects at appointments over the 16 week period.
|
|
Psychiatric disorders
Homicidal Ideation
|
2.2%
1/46 • Number of events 1 • 16 weeks
Adverse events were collected with a questionnaire of side effects at appointments over the 16 week period.
|
0.00%
0/46 • 16 weeks
Adverse events were collected with a questionnaire of side effects at appointments over the 16 week period.
|
Other adverse events
| Measure |
Zonisamide
n=46 participants at risk
Participants received zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose). Subjects may increase their dose to 600mg daily during the target treatment period if it is thought to be beneficial.
Zonisamide: Titration of dose to 500mg oral, daily, over 8 weeks, then 7 weeks of treatment at that dose
|
Placebo
n=46 participants at risk
Participants received placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group) Placebo: Placebo
|
|---|---|---|
|
Psychiatric disorders
Alcohol detoxification
|
4.3%
2/46 • Number of events 2 • 16 weeks
Adverse events were collected with a questionnaire of side effects at appointments over the 16 week period.
|
13.0%
6/46 • Number of events 6 • 16 weeks
Adverse events were collected with a questionnaire of side effects at appointments over the 16 week period.
|
Additional Information
Dr Albert Arias
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
Phone: 804-828-5793
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place