Trial Outcomes & Findings for Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse (NCT NCT01137890)

Last Updated: 2017-09-05

Results Overview

VAQ measures the change in effect after dose administration. Participants rate 6 items ("Any Drug Effect", "Rush", "Good Effects", "Bad Effects", "Liking", \& "Desire for Cocaine") by pointing an arrow along a 100-point line anchored at either end with "none" (0) \& "extremely" (100). Each participant's score is equal to the sum of all 6 ratings, \& the mean of all participant's scores is reported across each condition. The VAQ is only administered to subjects in the zonisamide (Zon) condition (n=8). Repeated within-subject measures ANOVA performed to observe the main effects of Zon dose (0, 300, \& 600mg) \& cocaine dose (1, 20, \& 40mg), \& their interaction. All 8 subjects who received Zon completed both 300mg \& 600mg doses. Assessments obtained on Week 1 (0mg Zon), Week 3 (300mg Zon), \& Week 5 (600mg Zon), in which all 3 cocaine were co-administered at these times. Cocaine not administered (only Zon) during Weeks 2 \& 4, thus no measures taken at these times

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Weeks 1-5; mean of weeks 1, 3 and 5 reported

Results posted on

2017-09-05

Participant Flow

Participant milestones

Participant milestones
Measure	Zonisamide Participants administered blind capsules containing either placebo or zonisamide. Zonisamide: Eight capsules administered daily in split doses at 22:00 and 09:00. Cocaine Hydrochloride: Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring. Neurocognitive and Performance Battery: Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment. Smoking Assessments: Participants answer questions about smoking and smoking behaviors are monitored.	Placebo Participants administered only placebo capsules containing lactose. Placebo: capsules administered in split doses at 22:00 and 09:00. Cocaine Hydrochloride: Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring. Neurocognitive and Performance Battery: Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment. Smoking Assessments: Participants answer questions about smoking and smoking behaviors are monitored.
Overall Study STARTED	14	5
Overall Study COMPLETED	8	2
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide n=8 Participants	Placebo n=4 Participants	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	38.9 years STANDARD_DEVIATION 5.6 • n=5 Participants	38.2 years STANDARD_DEVIATION 4.1 • n=7 Participants	38.7 years STANDARD_DEVIATION 5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 1-5; mean of weeks 1, 3 and 5 reported

Population: Because we are interested in how co-administered of cocaine-Zon affects this measure, only Zon participants are included (n=8). Each participant receives varying doses of Zon (0, 300, 600mg) at weeks 1, 2-3, 4-5, respectively. After getting used to each Zon dose, they are co-administered all 3 cocaine doses (1, 20, 40mg) during Weeks 1, 3, and 5

Outcome measures

Outcome measures
Measure	1mg-0mg n=8 Participants 1mg cocaine - 0mg zonisamide Both doses are expected to be inactive, thus this arm is viewed as Placebo	1mg-300mg n=8 Participants 1mg cocaine - 300mg zonisamide	1mg-600mg n=8 Participants 1mg cocaine - 600mg zonisamide	20mg-0mg n=8 Participants 20mg cocaine - 0mg zonisamide	20mg-300mg n=8 Participants 20mg cocaine - 300mg zonisamide	20mg-600mg n=8 Participants 20mg cocaine - 600mg zonisamide	40mg-0mg n=8 Participants 40mg cocaine - 0mg zonisamide	40mg-300mg n=8 Participants 40mg cocaine - 300mg zonisamide	40mg-600mg n=8 Participants 40mg cocaine - 600mg zonisamide	Day 10	Day 11	Day 12	Day 13	Day 14	Day 15	Day 16	Day 17	Day 18	Day 19	Day 20	Day 21	Day 22	Day 23	Day 24	Day 25	Day 26	Day 27	Day 28	Day 29	Day 30	Day 31	Day 32	Day 33	Day 34	Day 35	Day 36	Day 37	Day 38	Day 39
Change in Visual Analog Questionnaire (VAQ) Score	0.38 units on a scale Standard Deviation 0.74	3.75 units on a scale Standard Deviation 6.41	0.38 units on a scale Standard Deviation 0.74	40.63 units on a scale Standard Deviation 24.37	32.63 units on a scale Standard Deviation 14.78	30.00 units on a scale Standard Deviation 27.88	37.38 units on a scale Standard Deviation 21.84	29.75 units on a scale Standard Deviation 16.52	37.25 units on a scale Standard Deviation 25.47	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Weeks 1-5, mean of weeks 1, 3 and 5 reported

In each condition of cocaine-zonisamide dose, participants were asked to choose whether they would rather have a repeated cocaine dose (same dose as most recent administration) or cash of varying monetary value. The mean number of cocaine choices across each drug condition are reported. This measure only included participants in the zonisamide (Zon) condition (n=8), with each arm representing variation in co-administration of cocaine-Zon. Repeated within-subject measures ANOVA performed to observe the main effects of zonisamide dose (0, 300, and 600mg) and cocaine dose (1, 20, and 40mg), and their interaction. Only participants who received the active zonisamide medication (n=8) were included in this portion of the analysis. During self-administration sessions are every 15 min over 1hr45min period. Assessment on Weeks 1 (0mg Zon), 3 (300mg Zon), 5 (600mg Zon), in which varying cocaine doses co-administered. Cocaine not administered (only Zon) during Weeks 2 \& 4

Outcome measures

Outcome measures
Measure	1mg-0mg n=8 Participants 1mg cocaine - 0mg zonisamide Both doses are expected to be inactive, thus this arm is viewed as Placebo	1mg-300mg n=8 Participants 1mg cocaine - 300mg zonisamide	1mg-600mg n=8 Participants 1mg cocaine - 600mg zonisamide	20mg-0mg n=8 Participants 20mg cocaine - 0mg zonisamide	20mg-300mg n=8 Participants 20mg cocaine - 300mg zonisamide	20mg-600mg n=8 Participants 20mg cocaine - 600mg zonisamide	40mg-0mg n=8 Participants 40mg cocaine - 0mg zonisamide	40mg-300mg n=8 Participants 40mg cocaine - 300mg zonisamide	40mg-600mg n=8 Participants 40mg cocaine - 600mg zonisamide	Day 10	Day 11	Day 12	Day 13	Day 14	Day 15	Day 16	Day 17	Day 18	Day 19	Day 20	Day 21	Day 22	Day 23	Day 24	Day 25	Day 26	Day 27	Day 28	Day 29	Day 30	Day 31	Day 32	Day 33	Day 34	Day 35	Day 36	Day 37	Day 38	Day 39
Behavioral Choice Measures	0 number of cocaine choices Standard Deviation 0	0 number of cocaine choices Standard Deviation 0	0.25 number of cocaine choices Standard Deviation 0.71	2 number of cocaine choices Standard Deviation 2.67	2.38 number of cocaine choices Standard Deviation 2.33	2.25 number of cocaine choices Standard Deviation 2.05	3.5 number of cocaine choices Standard Deviation 2.93	3 number of cocaine choices Standard Deviation 2.2	3.38 number of cocaine choices Standard Deviation 2.39	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1-39

Population: Includes all participants analyzed (n=12; 8 zonisamide, 4 placebo)

Cocaine craving measured by Cocaine Selectivity Severity Assessment (CSSA). The CSSA is a reliable and valid tool to measure cocaine withdrawal severity within a 24 hr period, and has been shown to predict treatment response in a treatment setting. Participants are asked to rate 18-items on a Likert scale 0-7, with composite scores ranging 0-126 and higher numbers indicative of more severe withdrawal. Mean scores on CSSA across 39-day time period are reported.

Outcome measures

Outcome measures
Measure	1mg-0mg n=12 Participants 1mg cocaine - 0mg zonisamide Both doses are expected to be inactive, thus this arm is viewed as Placebo	1mg-300mg n=12 Participants 1mg cocaine - 300mg zonisamide	1mg-600mg n=12 Participants 1mg cocaine - 600mg zonisamide	20mg-0mg n=12 Participants 20mg cocaine - 0mg zonisamide	20mg-300mg n=12 Participants 20mg cocaine - 300mg zonisamide	20mg-600mg n=12 Participants 20mg cocaine - 600mg zonisamide	40mg-0mg n=12 Participants 40mg cocaine - 0mg zonisamide	40mg-300mg n=12 Participants 40mg cocaine - 300mg zonisamide	40mg-600mg n=12 Participants 40mg cocaine - 600mg zonisamide	Day 10 n=12 Participants	Day 11 n=12 Participants	Day 12 n=12 Participants	Day 13 n=12 Participants	Day 14 n=12 Participants	Day 15 n=12 Participants	Day 16 n=12 Participants	Day 17 n=12 Participants	Day 18 n=12 Participants	Day 19 n=12 Participants	Day 20 n=12 Participants	Day 21 n=12 Participants	Day 22 n=12 Participants	Day 23 n=12 Participants	Day 24 n=12 Participants	Day 25 n=12 Participants	Day 26 n=12 Participants	Day 27 n=12 Participants	Day 28 n=12 Participants	Day 29 n=12 Participants	Day 30 n=12 Participants	Day 31 n=12 Participants	Day 32 n=12 Participants	Day 33 n=12 Participants	Day 34 n=12 Participants	Day 35 n=12 Participants	Day 36 n=12 Participants	Day 37 n=12 Participants	Day 38 n=12 Participants	Day 39 n=12 Participants
Cocaine Craving Zonisamide	27.88 units on a scale Standard Deviation 10.25	27.25 units on a scale Standard Deviation 15.29	25 units on a scale Standard Deviation 14.32	19.13 units on a scale Standard Deviation 8.63	17.88 units on a scale Standard Deviation 11.51	13.5 units on a scale Standard Deviation 8	12.75 units on a scale Standard Deviation 11.21	12.13 units on a scale Standard Deviation 9.85	13.75 units on a scale Standard Deviation 10.93	9.63 units on a scale Standard Deviation 8.99	11.75 units on a scale Standard Deviation 9.18	14.25 units on a scale Standard Deviation 11.41	12.38 units on a scale Standard Deviation 10.86	23.63 units on a scale Standard Deviation 31.01	26.75 units on a scale Standard Deviation 39.46	24.88 units on a scale Standard Deviation 39.41	25.38 units on a scale Standard Deviation 38.93	24.13 units on a scale Standard Deviation 39.47	25.13 units on a scale Standard Deviation 39.67	12.75 units on a scale Standard Deviation 12.74	25.5 units on a scale Standard Deviation 29.82	15.25 units on a scale Standard Deviation 14.27	16.88 units on a scale Standard Deviation 12.05	13.88 units on a scale Standard Deviation 13.07	8.25 units on a scale Standard Deviation 9.41	10.25 units on a scale Standard Deviation 11	10.75 units on a scale Standard Deviation 10.17	7.63 units on a scale Standard Deviation 9.78	7.63 units on a scale Standard Deviation 10.82	6.57 units on a scale Standard Deviation 10.13	9.50 units on a scale Standard Deviation 9.09	11.25 units on a scale Standard Deviation 12.90	8.5 units on a scale Standard Deviation 10.43	13.5 units on a scale Standard Deviation 11.49	21.38 units on a scale Standard Deviation 17.74	8.13 units on a scale Standard Deviation 11.76	23.25 units on a scale Standard Deviation 35.25	8.25 units on a scale Standard Deviation 11.99	19.25 units on a scale Standard Deviation 27.22
Cocaine Craving Placebo	42.75 units on a scale Standard Deviation 11	41 units on a scale Standard Deviation 20.54	30.25 units on a scale Standard Deviation 23.49	28.25 units on a scale Standard Deviation 15.73	28.25 units on a scale Standard Deviation 14.57	26.5 units on a scale Standard Deviation 9.32	29.5 units on a scale Standard Deviation 6.35	27.25 units on a scale Standard Deviation 11.87	28.5 units on a scale Standard Deviation 13.82	19 units on a scale Standard Deviation 9.93	25.33 units on a scale Standard Deviation 5.85	25.25 units on a scale Standard Deviation 15.6	22.75 units on a scale Standard Deviation 5.12	22.75 units on a scale Standard Deviation 9.74	24.75 units on a scale Standard Deviation 14.5	19.25 units on a scale Standard Deviation 5.25	24.00 units on a scale Standard Deviation 11.53	22.5 units on a scale Standard Deviation 12.36	24.5 units on a scale Standard Deviation 15.86	26 units on a scale Standard Deviation 15.490	25.5 units on a scale Standard Deviation 18.21	23 units on a scale Standard Deviation 15.09	18 units on a scale Standard Deviation 9.17	19 units on a scale Standard Deviation 0	15.5 units on a scale Standard Deviation 0.70	16. units on a scale Standard Deviation 2.83	14.5 units on a scale Standard Deviation 2.12	16.5 units on a scale Standard Deviation 3.53	24 units on a scale Standard Deviation 0	16.5 units on a scale Standard Deviation 0.71	16.5 units on a scale Standard Deviation 0.71	19.5 units on a scale Standard Deviation 4.95	18. units on a scale Standard Deviation 2.83	17. units on a scale Standard Deviation 1.41	19. units on a scale Standard Deviation 7.07	16 units on a scale Standard Deviation 0	19 units on a scale Standard Deviation 4.24	20 units on a scale Standard Deviation 4.24	16.5 units on a scale Standard Deviation 2.12

SECONDARY outcome

Timeframe: Weeks 1-5; mean of weeks 1, 3 and 5 reported

Population: Because we are interested in how co-administration cocaine-zon affects this measure, only zon participants are included (n=8). Each participant receives varying doses of zon (0, 300, 600mg) at weeks 1, 2-3, 4-5, respectively. After getting used to each zon dose, they are co-administered all 3 cocaine doses (1, 20, 40mg) during Weeks 1, 3, and 5

Street Value of Sampled Dose. After co-administration of cocaine-zonisamide, participants were asked to hypothetically estimate the value of the drug they received, if they were to purchase it on the street. The mean value (dollars) across all drug conditions is reported here. Repeated within-subject measures ANOVA performed to observe the main effects of zonisamide dose (0, 300, and 600mg) and cocaine dose (0, 20, and 40mg), and their interaction. Only participants who received the active zonisamide medication (n=8) were included in this portion of the analysis. Additionally, all 8 subjects who received zonisamide completed both 300mg and 600mg doses. Within-subject repeated interval during self-administration sessions. Cocaine not administered (only Zon) during Weeks 2 \& 4, thus no measures taken at these times

Outcome measures

Outcome measures
Measure	1mg-0mg n=8 Participants 1mg cocaine - 0mg zonisamide Both doses are expected to be inactive, thus this arm is viewed as Placebo	1mg-300mg n=8 Participants 1mg cocaine - 300mg zonisamide	1mg-600mg n=8 Participants 1mg cocaine - 600mg zonisamide	20mg-0mg n=8 Participants 20mg cocaine - 0mg zonisamide	20mg-300mg n=8 Participants 20mg cocaine - 300mg zonisamide	20mg-600mg n=8 Participants 20mg cocaine - 600mg zonisamide	40mg-0mg n=8 Participants 40mg cocaine - 0mg zonisamide	40mg-300mg n=8 Participants 40mg cocaine - 300mg zonisamide	40mg-600mg n=8 Participants 40mg cocaine - 600mg zonisamide	Day 10	Day 11	Day 12	Day 13	Day 14	Day 15	Day 16	Day 17	Day 18	Day 19	Day 20	Day 21	Day 22	Day 23	Day 24	Day 25	Day 26	Day 27	Day 28	Day 29	Day 30	Day 31	Day 32	Day 33	Day 34	Day 35	Day 36	Day 37	Day 38	Day 39
Drug Value Questionnaire	0 dollars Standard Deviation 0	0 dollars Standard Deviation 0	0 dollars Standard Deviation 0	9.29 dollars Standard Deviation 7.32	8.50 dollars Standard Deviation 5.81	7.63 dollars Standard Deviation 3.54	16 dollars Standard Deviation 14.96	18.13 dollars Standard Deviation 18.31	9.5 dollars Standard Deviation 8.57	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Adverse Events

Zonisamide

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Annie Umbricht

Johns Hopkins University

Phone: 410-550-1917

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Zonisamide n=8 participants at risk Participants administered blind capsules containing either placebo or zonisamide. Zonisamide: Eight capsules administered daily in split doses at 22:00 and 09:00. Cocaine Hydrochloride: Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring. Neurocognitive and Performance Battery: Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment. Smoking Assessments: Participants answer questions about smoking and smoking behaviors are monitored.	Placebo n=4 participants at risk Participants administered only placebo capsules containing lactose. Placebo: capsules administered in split doses at 22:00 and 09:00. Cocaine Hydrochloride: Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring. Neurocognitive and Performance Battery: Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment. Smoking Assessments: Participants answer questions about smoking and smoking behaviors are monitored.
General disorders Allergic Rhinitis	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
General disorders Headache	75.0% 6/8 • Number of events 9 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	50.0% 2/4 • Number of events 4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
General disorders Inguinal Hernia	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
General disorders Skin Rash	0.00% 0/8 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	25.0% 1/4 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
General disorders Creatinine Elevation	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Cardiac disorders Palpitations	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Gastrointestinal disorders Appetite Decreased	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Gastrointestinal disorders Constipation	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	25.0% 1/4 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Gastrointestinal disorders Hepatitis	0.00% 0/8 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	50.0% 2/4 • Number of events 2 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Gastrointestinal disorders Indigestion	0.00% 0/8 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	25.0% 1/4 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Gastrointestinal disorders Liver function abnormal	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Gastrointestinal disorders Tooth Disease	50.0% 4/8 • Number of events 4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	50.0% 2/4 • Number of events 2 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Blood and lymphatic system disorders Anemia	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Blood and lymphatic system disorders Chemistry Abnormal	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Musculoskeletal and connective tissue disorders Back Pain	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Musculoskeletal and connective tissue disorders Pain lower extremity	0.00% 0/8 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	25.0% 1/4 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Nervous system disorders Tingling sensation in extremity	12.5% 1/8 • Number of events 2 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Nervous system disorders Agitation	0.00% 0/8 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	50.0% 2/4 • Number of events 2 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Nervous system disorders Dream abnormal	0.00% 0/8 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	50.0% 2/4 • Number of events 2 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Nervous system disorders Insomnia	25.0% 2/8 • Number of events 2 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Nervous system disorders Jittery	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Nervous system disorders Restlessness	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
General disorders Asthma	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	25.0% 1/4 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
General disorders Rhinitis	0.00% 0/8 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	25.0% 1/4 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
General disorders Athlete's foot	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Eye disorders Tinnitus	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.
Renal and urinary disorders Urethritis	12.5% 1/8 • Number of events 1 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.	0.00% 0/4 • 39 days Reported adverse events (AEs) include participants who were randomized into the study's conditions (zonisamide/placebo), and of which were rated as being either possibly, probably, or definitely related to the study. Although 19 participants were randomized, 9 did not complete. However, 2 of these provided sufficient data to be included in analyses. Thus, the possibility of study related AEs could only occur in 12 subjects (8 zonisamide, 4 placebo). This is the case for serious AEs, too.