Trial Outcomes & Findings for Zonisamide vs. Placebo in the Treatment of Alcohol Dependence (NCT NCT00595556)

Results Overview

This outcome measure represents the change in number of heavy drinking days (i.e., 5 or more drinks per day for men, and 4 or more per day for women)per week, from baseline to the end of week twelve. This was analyzed using weekly measurements over the 12 week study period (thirteen time points, 12 measurements)with a repeated measures analysis (SPSS linear mixed models), by interaction with time (week).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

baseline to the end of 12 weeks in treatment

Results posted on

2010-10-15

Participant Flow

Participant milestones

Participant milestones
Measure	Zonisamide Medication Treatment Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Overall Study STARTED	20	20
Overall Study COMPLETED	17	19
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Zonisamide vs. Placebo in the Treatment of Alcohol Dependence

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide Medication Treatment n=20 Participants Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo n=20 Participants Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=93 Participants	20 Participants n=4 Participants	40 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age Continuous	47.8 years STANDARD_DEVIATION 9.9 • n=93 Participants	50.4 years STANDARD_DEVIATION 11 • n=4 Participants	49.1 years STANDARD_DEVIATION 10 • n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	9 Participants n=4 Participants	17 Participants n=27 Participants
Sex: Female, Male Male	12 Participants n=93 Participants	11 Participants n=4 Participants	23 Participants n=27 Participants
Region of Enrollment United States	20 participants n=93 Participants	20 participants n=4 Participants	40 participants n=27 Participants

PRIMARY outcome

Timeframe: baseline to the end of 12 weeks in treatment

This outcome measure represents the change in number of heavy drinking days (i.e., 5 or more drinks per day for men, and 4 or more per day for women)per week, from baseline to the end of week twelve. This was analyzed using weekly measurements over the 12 week study period (thirteen time points, 12 measurements)with a repeated measures analysis (SPSS linear mixed models), by interaction with time (week).

Outcome measures

Outcome measures
Measure	Zonisamide Medication Treatment n=20 Participants Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo n=20 Participants Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Change in Number of Heavy Drinking Days (i.e., 5 or More Drinks Per Day for Men, and 4 or More Per Day for Women)Per Week, by Week	-.30 Days/week Standard Deviation .362	-.20 Days/week Standard Deviation .362

PRIMARY outcome

Timeframe: baseline to the end of 12 weeks in treatment

This outcome measure analyzed the weekly rate of change in number of abstinent days over the twelve weeks of the study from baseline to the end of week twelve. This was analyzed using weekly measurements over the 12 week study period (thirteen time points, 12 measurements)with a repeated measures analysis (SPSS proc mixed), by interaction with time (week).

Outcome measures

Outcome measures
Measure	Zonisamide Medication Treatment n=20 Participants Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo n=20 Participants Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Weekly Rate of Change in Abstinent Days	0.17 days/week Standard Error .02	0.13 days/week Standard Error .02

SECONDARY outcome

Timeframe: baseline to the end of 12 weeks in treatment

Population: The analysis was intention to treat and last observation carried forward

This outcome measure represents the change in the total number of standard drinks per week (weekly data) from baseline to the end of week twelve. This was analyzed using weekly measurements from baseline to week 12 week of the study period (thirteen time points, 12 measurements)with a repeated measures analysis (SPSS linear mixed models), by interaction with time (week).

Outcome measures

Outcome measures
Measure	Zonisamide Medication Treatment n=20 Participants Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo n=20 Participants Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Change in Number of Drinks Per Week by Week	-2.2 drinks/week Standard Deviation 20.5	-1.4 drinks/week Standard Deviation 20.5

SECONDARY outcome

Timeframe: baseline to the end of 12 weeks in treatment

This is the change in measured urge to drink alcohol as measured by the Alcohol Urge Questionnaire (AUQ), measured every 2 weeks from baseline until the last week of the study (over twelve weeks, 7 timepoint measurements of AUQ, 6 calculated changes). It is reported in terms of change per visit (every 2 weeks). AUQ measures a feeling state, and uses a 7 point (1-7)Likert scale for each of 8 items (questions). The lowest urge score is 8 (representing less urge to drink), and the highest would be tabulated as 56 (meaning more urge to drink). Repeated measures SPPS linear mixed models used.

Outcome measures

Outcome measures
Measure	Zonisamide Medication Treatment n=20 Participants Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo n=20 Participants Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Change in the Urge to Drink Alcohol as Measured by the Alcohol Urge Questionnaire (AUQ)	-1.4 units on a scale/visit Standard Deviation 1	-0.6 units on a scale/visit Standard Deviation 1

SECONDARY outcome

Timeframe: 12 weeks (from initiation to end of treatment)

This outcome measure looks at the change in blood levels of this enzyme assay from baseline, and then after 6 weeks (midpoint), and then at the endpoint (12 weeks). The analysis takes into account all three time points, and reports the average change between each of the three time points.

Outcome measures

Outcome measures
Measure	Zonisamide Medication Treatment n=20 Participants Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo n=20 Participants Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Change in Gamma-glutamyl Transferase (GGT) Concentration	8.4 Units/Liter Standard Deviation 36.2	2.9 Units/Liter Standard Deviation 36.2

Adverse Events

Zonisamide Medication Treatment

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Zonisamide Medication Treatment n=20 participants at risk Subjects in this arm received the zonisamide anticonvulsant medication in double blind fashion starting with 100mg daily and titrated every other week to a target dose of 500mg daily. The pills were over-encapsulated to match the placebo.	Placebo n=20 participants at risk Subjects in this arm received a double blind placebo lactose capsule identical to the over-capsule on the actual medicine. The titration of "dose" and number of pills matched that of the zonisamide arm.
Gastrointestinal disorders GI	65.0% 13/20 • Number of events 16 • 14 weeks	20.0% 4/20 • Number of events 5 • 14 weeks
Nervous system disorders Neurologic	40.0% 8/20 • Number of events 10 • 14 weeks	25.0% 5/20 • Number of events 5 • 14 weeks
Psychiatric disorders Psychiatric	20.0% 4/20 • Number of events 4 • 14 weeks	40.0% 8/20 • Number of events 14 • 14 weeks
Nervous system disorders Cognitive	20.0% 4/20 • Number of events 4 • 14 weeks	10.0% 2/20 • Number of events 2 • 14 weeks
Reproductive system and breast disorders Genitourinary	20.0% 4/20 • Number of events 4 • 14 weeks	10.0% 2/20 • Number of events 2 • 14 weeks
General disorders Fatigue/Somnolence	20.0% 4/20 • Number of events 6 • 14 weeks	5.0% 1/20 • Number of events 1 • 14 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal	10.0% 2/20 • Number of events 2 • 14 weeks	10.0% 2/20 • Number of events 2 • 14 weeks

Additional Information

Albert J. Arias, M.D.

UCHC

Phone: 8606794423

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place