Trial Outcomes & Findings for Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action (NCT NCT02900352)

Last Updated: 2022-10-13

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

COMPLETED

Study phase

PHASE3

Target enrollment

156 participants

Primary outcome timeframe

over 8 weeks (weeks 9-16)

Results posted on

2022-10-13

Participant Flow

Participant milestones

Participant milestones
Measure	Zonisamide Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 7 weeks, then 9 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 Patients will receive 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	77	79
Overall Study COMPLETED	49	62
Overall Study NOT COMPLETED	28	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Zonisamide Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind (Titration of dose to 500mg oral, daily, over 7 weeks, then 9 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 Patients will receive 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 Lost to Follow-up	28	17

Baseline Characteristics

Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide n=77 Participants Subjects will receive 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=79 Participants Patients will receive 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	Total n=156 Participants Total of all reporting groups
Age, Continuous	51.2 years STANDARD_DEVIATION 11.6 • n=5 Participants	51.9 years STANDARD_DEVIATION 9.7 • n=7 Participants	51.5 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	27 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	52 Participants n=7 Participants	98 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	70 Participants n=5 Participants	75 Participants n=7 Participants	145 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	63 Participants n=5 Participants	66 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	77 participants n=5 Participants	79 participants n=7 Participants	156 participants n=5 Participants

PRIMARY outcome

Timeframe: over 8 weeks (weeks 9-16)

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

Outcome measures
Measure	Zonisamide n=77 Participants Subjects will receive 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=79 Participants Patients will receive 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	19.7 Number of drinks per week Standard Error 2.2	23.7 Number of drinks per week Standard Error 1.98

SECONDARY outcome

Timeframe: over the last 8 weeks (weeks 9-16)

percentage of subjects with no heavy drinking days (PSNHDD) The PSNHDD can be derived from each subject's Timeline Followback (TLFB) data.

Outcome measures

Outcome measures
Measure	Zonisamide n=77 Participants Subjects will receive 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=79 Participants Patients will receive 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	8.97 Percentage of participants	5.13 Percentage of participants

SECONDARY outcome

Timeframe: over 16 weeks (weeks 1-16)

Population: Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants or collected at slightly different timepoints. Results are reported for all participants for whom data is available.

Difference between groups on levels of GGT over time from baseline to endpoint, which will includes two interim data points for a total of four time points. This will analyzed with a mixed models longitudinal analysis (repeated measures). Levels are in Units per Liter.

Outcome measures

Outcome measures
Measure	Zonisamide n=74 Participants Subjects will receive 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=77 Participants Patients will receive 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) Levels Baseline Visit	78.35 International Units per Liter (UI/L) Standard Error 12.10	71.88 International Units per Liter (UI/L) Standard Error 11.12
Gamma Glutamyl Transferase (GGT) Levels Visit 5 (Week 5)	52.33 International Units per Liter (UI/L) Standard Error 23.7	64.4 International Units per Liter (UI/L) Standard Error 29.35
Gamma Glutamyl Transferase (GGT) Levels Visit 7 (Week 9)	59.49 International Units per Liter (UI/L) Standard Error 10.05	70.24 International Units per Liter (UI/L) Standard Error 24.43
Gamma Glutamyl Transferase (GGT) Levels Visit 9 (Week 13)	16.0 International Units per Liter (UI/L) Standard Error 0.0	25.75 International Units per Liter (UI/L) Standard Error 5.75
Gamma Glutamyl Transferase (GGT) Levels Visit 10 (Week 16)	54.48 International Units per Liter (UI/L) Standard Error 7.83	56.65 International Units per Liter (UI/L) Standard Error 10.23

SECONDARY outcome

Timeframe: over the last 8 weeks (weeks 9-16)

Population: Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available.

The difference in the number of heavy drinking days per week compared between groups (zonisamide and placebo) for the last 8 weeks of treatment (during the time spent on the target dose of the medication). Performed using a mixed models longitudinal analysis (repeated measures).

Outcome measures

Outcome measures
Measure	Zonisamide n=59 Participants Subjects will receive 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=71 Participants Patients will receive 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	2.7 Number of heavy drinking days/week Standard Error .34	3.3 Number of heavy drinking days/week Standard Error .30

SECONDARY outcome

Timeframe: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up

Population: Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available.

This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures Min value: 8 Max value: 42 higher score = worse craving

Outcome measures

Outcome measures
Measure	Zonisamide n=58 Participants Subjects will receive 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=67 Participants Patients will receive 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 Alcohol Urge Questionnaire Score (AUQ) Visit 2 (Baseline)	16.2 score on a scale Standard Deviation 1.04	16.06 score on a scale Standard Deviation 1.04
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 3 (Week 1)	14.4 score on a scale Standard Deviation 0.96	17.12 score on a scale Standard Deviation 1.2
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 4 (Week 3)	15.2 score on a scale Standard Deviation 1.12	15.28 score on a scale Standard Deviation 0.96
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 5 (Week 5)	13.84 score on a scale Standard Deviation 1.09	14.4 score on a scale Standard Deviation 1
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 6 (Week 7)	12.8 score on a scale Standard Deviation 0.96	14.72 score on a scale Standard Deviation 1.04
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 7 (Week 9)	14.08 score on a scale Standard Deviation 1.2	16.24 score on a scale Standard Deviation 1.12
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 8 (Week 11)	13.6 score on a scale Standard Deviation 1.2	14.56 score on a scale Standard Deviation 1.12
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 9 (Week 13)	13.6 score on a scale Standard Deviation 1.2	14.4 score on a scale Standard Deviation 0.96
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 10 (Week 16)	13.36 score on a scale Standard Deviation 1.2	13.36 score on a scale Standard Deviation .96
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 11 (2 Week follow up)	14.56 score on a scale Standard Deviation .17	14.32 score on a scale Standard Deviation 1.04
Change in Alcohol Urge Questionnaire Score (AUQ) Visit 12 (3 Month follow up)	14.16 score on a scale Standard Deviation 1.28	13.68 score on a scale Standard Deviation .96

SECONDARY outcome

Timeframe: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up

Population: Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available.

Change in quality of life scores measured by the Q-LES-Q. ' Min: 16 Max: 80 Higher Scores = Higher Life Enjoyment

Outcome measures

Outcome measures
Measure	Zonisamide n=60 Participants Subjects will receive 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=60 Participants Patients will receive 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 Visit 2 (Baseline)	60 score on a scale Standard Error 13.6	59.84 score on a scale Standard Error 12.48
Change in Quality of Life Visit 10 (Week 16)	61.6 score on a scale Standard Error 1.6	63.2 score on a scale Standard Error 13.44
Change in Quality of Life Visit 11 (2 Week Follow up)	68 score on a scale Standard Error 2.96	60.48 score on a scale Standard Error 2.72
Change in Quality of Life Visit 12 (3 Month Follow up)	65.12 score on a scale Standard Error 12.96	64.64 score on a scale Standard Error 13.76

SECONDARY outcome

Timeframe: over 16 weeks (weeks 1-16) and at 2 week and 3 month follow up

Population: Due to protocol changes over the course of the study, data for some outcomes was not collected for all participants. Results are reported for all participants for whom data is available.

level of alcohol-related problems measured by the Short Index of Problems (SIP), total score Min score: 0 Max Score: 45 Higher score= more problems

Outcome measures

Outcome measures
Measure	Zonisamide n=50 Participants Subjects will receive 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=58 Participants Patients will receive 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 Visit 2 (Baseline)	14.94 score on a scale Standard Error 1.13	16.4 score on a scale Standard Error .94
Level of Alcohol-related Problems Visit 10 (Week 16)	8.32 score on a scale Standard Error 1.23	11.6 score on a scale Standard Error 1.03
Level of Alcohol-related Problems Visit 12 (3 Month follow up)	6.92 score on a scale Standard Error 1.08	9.69 score on a scale Standard Error 1.18

Adverse Events

Zonisamide

Serious events: 2 serious events

Other events: 73 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 76 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Zonisamide n=77 participants at risk Subjects will receive 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=79 participants at risk Patients will receive 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
Cardiac disorders Stroke	1.3% 1/77 • Number of events 1 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods	0.00% 0/79 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods
Psychiatric disorders Alcohol Withdrawal	0.00% 0/77 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods	1.3% 1/79 • Number of events 1 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods
Injury, poisoning and procedural complications Motor Vehicle Accident	0.00% 0/77 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods	1.3% 1/79 • Number of events 1 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods
Psychiatric disorders Suicidal Ideation	1.3% 1/77 • Number of events 1 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods	0.00% 0/79 • Duration of the study (16 weeks) Patients provided subjective reports of side effects at each study visit using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview, a widely used measure of adverse events. Complex adverse events may have also been recorded using non-systematic methods

Other adverse events

Additional Information

Dr. Albert Arias

Virginia Commonwealth University

Phone: 8048285793

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place