Assessing The Long-Term Safety And To Explore The Long-Term Efficacy Of Zonisamide As Monotherapy In Newly Diagnosed Partial Seizures

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00848549
• Collaborator: (none)
• Enrollment: 295
• Locations: 133
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the long-term safety and tolerability and to explore the long-term efficacy of zonisamide as monotherapy treatment in subjects with newly diagnosed partial seizures.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Zonisamide; Drug: Carbamazepine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 295 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind Extension Study To Assess The Long-Term Safety And To Explore The Long-Term Efficacy Of Zonisamide As Monotherapy In Newly Diagnosed Partial Seizures
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ZNS	Drug: Zonisamide; Subjects will start on the same dose that was achieved at the end of study E2090-E044-310. Maximum daily dose allowable is 500 mg; the minimum daily dose allowable is 200 mg. During the study, subjects will be titrated up or down depending on seizure-free status or intolerability/adverse events, respectively. Should a dose outside of the maximum be required the subject will be with drawn and gradually down titrated by 100 mg per week.; Other Names: Zonegran
Active Comparator: CBZ	Drug: Carbamazepine; Subjects will start on the same dose that was achieved at the end of study E2090-E044-310. Maximum daily dose allowable is 1200 mg; the minimum daily dose allowable is 400 mg. During the study, subjects will be titrated up or down depending on seizure-free status or intolerability/adverse events respectively. Should a dose outside of the maximum be required the subject will be with drawn and gradually down titrated by 200 mg per week.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Remaining in the Study at Each Visit [At 3, 6, 9, 12, 15, 18, 21, 24, and 27 months]

   The retention rate is defined as the percentage of subjects remaining on the study at each visit, starting from the first dose of study drug in the extension phase.

Secondary Outcome Measures

1. Time to Drop-out Due to Lack of Efficacy [Week 1 to Week 109 (in core study) and Month 1 to Month 27 (in extension study)]

   Lack of efficacy was if the subject had poor seizure control (defined as experiencing a seizure despite being on the maximum dose for = 2 weeks). The subject could withdraw at any time due to lack of efficacy.

2. Time to Drop-out Due to Adverse Event (AE) [Week 1 to Week 109 (in base study) and Month 1 to Month 27 (in extension study)]

   Adverse events in study subjects included any change in the subject's condition. This includes symptoms, physical findings, or clinical syndromes. All AEs that occurred after signing of informed consent through the last visit and for 15 days following study drug discontinuation were captured on the AE Case Report Form (CRF).

3. Percentage of Participants That Are Seizure Free for at Least 24 Month Consecutive Period in the Base Study and Extension Phase [Week 5 to Week 109 (in base study) and Month 1 to Month 27 (in extension phase)]

   The number of participants that have remained seizure free for at least a 24 month consecutive period from the start of the Flexible Dosing Period (FDP: the period following the Titration Period and leading into the Maintenance Period) in the base study through the treatment period of this study. Seizure freedom was defined as the absence of all seizure regardless of seizure type.

4. Change From Baseline in Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) Overall Score at Each Visit [Weeks 0, 26, 52, 78 and 117]

   The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry,emotional well being,energy/fatigue, cognitive functioning, medication effects, social functioning,overall QOL. The overall score is derived by weighing and then summing the 7 domain scores. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are converted to 0-100 point scores; higher converted scores always reflect better QOL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 78 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has completed study E2090-E044-310.

2. Subject is able and willing to give written informed consent.

3. Female subjects without childbearing potential (two years post-menopausal, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects of childbearing potential must be non-pregnant, non-lactating and abide by one of the following medically acceptable contraceptive measures: oral contraceptive pill, contraceptive injections, implants or patches, intrauterine device in place for at least three months, vasectomised partner or abstinence throughout the study and for one month after discontinuation of study medication. When the contraceptive pill is used, this should contain no less than 50 μg oestrogen.

4. The subject is able and willing to follow the investigational study procedures, maintain a seizure diary and report adverse events.

Exclusion Criteria:

1. Subject has a history of a significant or currently uncontrolled disease that will contraindicate the use of the study drugs or interfere with the conduct of this study and/or the assessment of safety and efficacy of the study drugs.

2. Subject has a body weight <40 kg.

3. Subject has a newly occurring progressive malignancy during study E2090-E044-310 (excluding a history of non-metastasized and adequately treated cutaneous squamous cell carcinoma).

4. Subject has developed a psychiatric illness or mood disorder requiring electro-convulsive or drug therapy within the previous 6 months and is considered uncontrolled; history of suicide attempt, alcohol or drug abuse, chronic treatment with benzodiazepines or barbiturates.

5. Subject is currently taking carbonic anhydrase inhibitors.

6. Subject developed pancreatitis, nephrolithiasis or hypercalcuria, clinically significant laboratory abnormalities, stroke or uncontrolled hypertension during study E2090-E044-310.

7. Subject is currently taking monoamine oxidase inhibitors (MAOIs) or any other excluded medications (see protocol section 9.9.3).

8. Subject has a history of allergy to carbamazepine or to zonisamide or to any of their ingredients or to sulphonamides.

9. Subject has developed a bone marrow depression, low platelet count or other blood dyscrasias.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Camperdown	New South Wales	Australia	2050
2		Bedford Park	South Australia	Australia	5042
3		Clayton	Victoria	Australia	3168
4		Fitzroy	Victoria	Australia	3065
5		Heidelberg West	Victoria	Australia	3084
6		Parkville	Victoria	Australia	3050
7		Perth	Western Australia	Australia	6000
8		Queensland		Australia	4558
9		Aalborg		Denmark	9000
10		Bethune cedex		France	62408
11		Dijon cedex		France	21033
12		Paris		France	75651
13		St Etienne cedex 2		France	42055
14		Berlin		Germany	13353
15		Bochum		Germany	44805
16		Duesseldorf		Germany	40212
17		Munich		Germany	81377
18		Schwerin		Germany	19053
19		Westerstede		Germany	26676
20		Athens		Greece	10676
21		Athens		Greece	11525
22		Athens		Greece	15562
23		Patras		Greece	26500
24		Thessaloniki		Greece	54636
25		Thessaloniki		Greece	55236
26		Thessaloniki		Greece	57010
27		Budapest		Hungary	1076
28		Budapest		Hungary	1096
29		Budapest		Hungary	1145
30		Debrecen		Hungary	4032
31		Gyula		Hungary	5700
32		Hodmezovasarhely		Hungary	6800
33		Nyregyhaza		Hungary	4400
34		Zalaegerszeg-Poozva		Hungary	8908
35		Bangalore		India	560034
36		Bangalore		India	560094
37		Hyderabad		India	500 001
38		Koturpuram, Chennai		India	600 085
39		Madurai, Tamil Nadu		India	625 020
40		Mumbai		India	400 012
41		New - Delhi		India	110095
42		New Delhi		India	110 016
43		New Delhi		India	110 065
44		Pune		India	411 030
45		Catanzaro		Italy	88100
46		Messina		Italy	98122
47		Milan		Italy	20132
48		Monza (MI)		Italy	20052
49		Orbassano		Italy	10043
50		Pavia		Italy	27100
51		Rome		Italy	00133
52		Siena		Italy	53100
53		Turin		Italy	10126
54		Udine		Italy	33100
55		Anyang		Korea, Republic of	431-070
56		Seoul		Korea, Republic of	110-744
57		Seoul		Korea, Republic of	133-792
58		Seoul		Korea, Republic of	143-729
59		Wonju		Korea, Republic of	220-701
60		Podgorica		Montenegro	81000
61		Gdansk		Poland	80-803
62		Gdansk		Poland	80266
63		Katowice		Poland	40752
64		Krakow		Poland	31-530
65		Lodz		Poland	90-153
66		Lodz		Poland	93-513
67		Lublin		Poland	20-718
68		Poznan		Poland	60-355
69		Sosnowiec		Poland	41-200
70		Szczecin		Poland	71252
71		Warszawa		Poland	00-416
72		Warszawa		Poland	09-777
73		Kaliningrad		Russian Federation	236000
74		Kazan		Russian Federation	420012
75		Madrid		Russian Federation	28038
76		Moscow		Russian Federation	117049
77		Moscow		Russian Federation	117995
78		Moscow		Russian Federation	198103
79		Saint Petersburg		Russian Federation	194044
80		Saint-Petersburg		Russian Federation	194017
81		Saint-Petersburg		Russian Federation	197376
82		Yaroslavl		Russian Federation	160000
83		Belgrade		Serbia	11000
84		Kragujevac		Serbia	34000
85		Krusevac		Serbia	37000
86		Nis		Serbia	18000
87		Novi Sad		Serbia	21000
88		Sombor		Serbia	25000
89		Subotica		Serbia	24000
90		Bratislava		Slovakia	80000
91		Bratislava		Slovakia	826 06
92		Bratislava		Slovakia	833 05
93		Brezno		Slovakia	97701
94		Kosice		Slovakia	4190
95		NoveZamky		Slovakia	940 34
96		Spitalska 6		Slovakia	94901
97		Vranov nad Toplou		Slovakia	093 27
98		Zilina		Slovakia	1207
99		Bellair		South Africa	4001
100		Berea		South Africa	4001
101		Parktown		South Africa	2193
102		Pretoria		South Africa	0041
103		Richards Bay		South Africa	3900
104		Sandton		South Africa	2196
105		Tygerberg		South Africa	7505
106		Umhlanga		South Africa	4320
107		Alicante		Spain	03010
108		Barcelona		Spain	08041
109		Cruces (Vizcaya)		Spain	48903
110		Madrid		Spain	28040
111		Madrid		Spain	28047
112		Malaga		Spain	29010
113		Oviedo		Spain	33006
114		Sevilla		Spain	41009
115		Sevilla		Spain	41013
116		Sevilla		Spain	41014
117		Zaragoza		Spain	50009
118		Goteborg		Sweden	41345
119		Linkoping		Sweden	SE-58185
120		Lund		Sweden	22185
121		Basel		Switzerland	4031
122		Berne		Switzerland	3010
123		St Gallen		Switzerland	9007
124		Changhua		Taiwan	50006
125		Kaohsiung		Taiwan	80099
126		Tao-Yuan		Taiwan	33305
127		Yong Kang		Taiwan	71004
128		Bristol		United Kingdom	BS16 1LE
129		Cardiff		United Kingdom	CF144XN
130		Glasgow		United Kingdom	G11 6NT
131		Liverpool		United Kingdom	L9 7AJ
132		Tooting		United Kingdom	SW17 0QT
133		Treliske		United Kingdom	TR1 3LJ

Sponsors and Collaborators

• Eisai Inc.

Investigators

• Principal Investigator: Michel Baulac, Hopital de la Pitie-Saltpetriere

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT00848549
• Other Study ID Numbers: E2090-E044-314; 2008-001159-23
• First Posted: Feb 20, 2009
• Last Update Posted: Dec 24, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Eisai Inc.: Epilepsy; Monotherapy
• Additional relevant MeSH terms: Epilepsy; Seizures; Carbamazepine; Zonisamide

Study Results

Participant Flow

Recruitment Details	E2090-E044-314 is a double-blind extension of E2090-E044-310 (NCT00477295) "base study." Assessment of eligibility took place at the Study Entry Visit (SEV), which was the same day as their final visit of Study 310. Subjects remained on the same investigational product as they were randomized to in Study 310 until unblinding of that study.

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the core study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Subjects received the same study drug to which they had been randomized in the core study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.
Period Title: E2090-E044-310 (Base Study) Disposition
STARTED	282	301
COMPLETED	161	192
NOT COMPLETED	121	109
Period Title: E2090-E044-310 (Base Study) Disposition
STARTED	161	192
COMPLETED	137	158
NOT COMPLETED	24	34
Period Title: E2090-E044-310 (Base Study) Disposition
STARTED	137	158
COMPLETED	120	134
NOT COMPLETED	17	24

Baseline Characteristics

Arm/Group Title	Zonisamide	Carbamazepine	Total
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the core study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Subjects received the same study drug to which they had been randomized in the core study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Total of all reporting groups
Overall Participants	282	301	583
Age (years) [Mean (Standard Deviation) ]
Base Study 310 (NCT00477295, n=583)	37.1 (16.33)	35.6 (15.50)	36.35 (15.92)
Extension Study 314 (NCT00848549, n=295)	37.8 (16.13)	34.4 (14.93)	36.1 (15.53)
Sex/Gender, Customized (participants) [Number]
Female (Base Study 310, NCT00477295)	107 37.9%	128 42.5%	235 40.3%
Male (Base Study 310, NCT00477295)	174 61.7%	172 57.1%	346 59.3%
Female (Extension Study 314, NCT00848549)	57 20.2%	59 19.6%	116 19.9%
Male (Extension Study 314, NCT00848549)	80 28.4%	99 32.9%	179 30.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Remaining in the Study at Each Visit
Description	The retention rate is defined as the percentage of subjects remaining on the study at each visit, starting from the first dose of study drug in the extension phase.
Time Frame	At 3, 6, 9, 12, 15, 18, 21, 24, and 27 months

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) Population is defined as all subjects who received at least one dose of investigational product(IP)

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.
Measure Participants	137	158
3 months	95.6 33.9%	93.7 31.1%
6 months	87.6 31.1%	84.2 28%
9 months	76.6 27.2%	75.3 25%
12 months	58.4 20.7%	61.4 20.4%
15 months	38.7 13.7%	43.7 14.5%
18 months	27.7 9.8%	27.8 9.2%
21 months	13.1 4.6%	12.7 4.2%
24 months	5.8 2.1%	2.5 0.8%
27 months	1.5 0.5%	0.6 0.2%

2. Secondary Outcome

Title	Time to Drop-out Due to Lack of Efficacy
Description	Lack of efficacy was if the subject had poor seizure control (defined as experiencing a seizure despite being on the maximum dose for = 2 weeks). The subject could withdraw at any time due to lack of efficacy.
Time Frame	Week 1 to Week 109 (in core study) and Month 1 to Month 27 (in extension study)

Outcome Measure Data

Analysis Population Description

310 ITT Population (combined ITT Population from basecore study and extension phase). 24 participants were discontinued in each arm due to lack of efficacy; these were the participants that were evaluated in this outcome.

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.
Measure Participants	24	24
Mean (Standard Deviation) [Days]	297.9 (170.03)	289.0 (108.93)

3. Secondary Outcome

Title	Time to Drop-out Due to Adverse Event (AE)
Description	Adverse events in study subjects included any change in the subject's condition. This includes symptoms, physical findings, or clinical syndromes. All AEs that occurred after signing of informed consent through the last visit and for 15 days following study drug discontinuation were captured on the AE Case Report Form (CRF).
Time Frame	Week 1 to Week 109 (in base study) and Month 1 to Month 27 (in extension study)

Outcome Measure Data

Analysis Population Description

310 ITT Population (33 participants were discontinued in the Zonisamide arm and 35 were discontinued in the Carbamazepine arm; these were the participants evaluated for this outcome)

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.
Measure Participants	33	35
Mean (Standard Deviation) [Days]	131.9 (166.90)	97.2 (114.47)

4. Secondary Outcome

Title	Percentage of Participants That Are Seizure Free for at Least 24 Month Consecutive Period in the Base Study and Extension Phase
Description	The number of participants that have remained seizure free for at least a 24 month consecutive period from the start of the Flexible Dosing Period (FDP: the period following the Titration Period and leading into the Maintenance Period) in the base study through the treatment period of this study. Seizure freedom was defined as the absence of all seizure regardless of seizure type.
Time Frame	Week 5 to Week 109 (in base study) and Month 1 to Month 27 (in extension phase)

Outcome Measure Data

Analysis Population Description

310 ITT Population

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.
Measure Participants	281	300
Number (95% Confidence Interval) [Percentage of Participants]	32.3 11.5%	35.2 11.7%

5. Secondary Outcome

Title	Change From Baseline in Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) Overall Score at Each Visit
Description	The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry,emotional well being,energy/fatigue, cognitive functioning, medication effects, social functioning,overall QOL. The overall score is derived by weighing and then summing the 7 domain scores. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are converted to 0-100 point scores; higher converted scores always reflect better QOL.
Time Frame	Weeks 0, 26, 52, 78 and 117

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Zonisamide	Carbamazepine
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.	Subjects received the same study drug to which they had been randomized in the base study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.
Measure Participants	137	158
Week 0	4.697 (16.254)	7.101 (13.781)
Week 26	6.101 (16.566)	10.956 (14.940)
Week 52	8.602 (14.326)	11.687 (13.653)
Week 78	4.287 (15.566)	1.902 (13.495)
Week 117	-0.292 (17.332)	15.849 (12.302)

Adverse Events

Time Frame	From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation.
Adverse Event Reporting Description	Adverse events were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations.
Arm/Group Title	Zonisamide (Extension Study 314, NCT00848549)		Carbamazepine (Extension Study 314, NCT00848549)		Zonisamide (Base Study 310, NCT00477295)		Carbamazepine (Base Study 310, NCT00477295)
Arm/Group Description	Subjects received the same study drug to which they had been randomized in the core study phase and remained on their final dose for the start of the extension phase (between 200 mg and 500 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.		Subjects received the same study drug to which they had been randomized in the core study phase and remained on their final dose for the start of the extension phase (between 400 mg and 1200 mg per day). Flexible dosing was permitted as symptoms changed as long as it stayed within the dosing range.		The starting dose in this arm was zonisamide 100mg daily. The dose during the Titration Period (4 weeks) ranged from 100 to 200mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 300 to 500mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.		The starting dose in this arm was carbamazepine 200mg daily. The dose during the Titration Period (4 weeks) ranged from 200 to 400mg daily. During the Flexible Dosing Period (FDP), the subjects were given doses ranging from 600 to 1200mg daily or if they could not tolerate that dose, were allowed one down-titration or were withdrawn. If the subjects remained seizure-free for 26 weeks by the end of FDP (the subject was allowed 3 chances to achieve this), they entered the Maintenance Period (26 weeks), where they remained on the same dose they were taking at the end of the FDP.
All Cause Mortality
	Zonisamide (Extension Study 314, NCT00848549)		Carbamazepine (Extension Study 314, NCT00848549)		Zonisamide (Base Study 310, NCT00477295)		Carbamazepine (Base Study 310, NCT00477295)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Zonisamide (Extension Study 314, NCT00848549)		Carbamazepine (Extension Study 314, NCT00848549)		Zonisamide (Base Study 310, NCT00477295)		Carbamazepine (Base Study 310, NCT00477295)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/137 (5.1%)		7/158 (4.4%)		15/281 (5.3%)		17/300 (5.7%)
Cardiac disorders
Myocardial ischaemia	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Bradycardia	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Myocardial infarction	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Ear and labyrinth disorders
Vertigo	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Gastrointestinal disorders
Abdominal pain	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Duodenal ulcer haemorrhage	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Peptic ulcer haemorrhage	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Gastric ulcer	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
General disorders
Death	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Pyrexia	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Hepatobiliary disorders
Cholecystitis	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Cholelithiasis	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Infections and infestations
Upper respiratory tract infection	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Viral infection	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Appendicitis	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Chronic sinusitis	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Sinusitis bacterial	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Typhoid fever	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Injury, poisoning and procedural complications
Clavicle fracture	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Subarachnoid haemorrhage	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Facial bones fracture	0/137 (0%)		0/158 (0%)		0/281 (0%)		2/300 (0.7%)
Femur fracture	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Head injury	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Humerus fracture	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Joint dislocation	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Muscle strain	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Radius fracture	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Skull fracture	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Investigations
Electrocardiogram abnormal	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Hepatic enzyme increased	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Metabolism and nutrition disorders
Hyponatraemia	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Hypokalaemia	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Bone pain	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Musculoskeletal pain	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Brain neoplasm	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Prostate cancer	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Nervous system disorders
Ataxia	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Carotid artery stenosis	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Somnolence	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Transient ischaemic attack	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Partial seizures with secondary generalization	0/137 (0%)		0/158 (0%)		0/281 (0%)		4/300 (1.3%)
Complex partial seizures	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Convulsion	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Epilepsy	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Ischaemic stroke	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Partial seizures	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Pregnancy, puerperium and perinatal conditions
Unwanted pregnancy	0/137 (0%)		1/158 (0.6%)		0/281 (0%)		0/300 (0%)
Psychiatric disorders
Acute psychosis	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Suicidal ideation	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Suicide attempt	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Respiratory disorder	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Rhinitis hypertrophic	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Skin and subcutaneous tissue disorders
Rash	0/137 (0%)		0/158 (0%)		0/281 (0%)		2/300 (0.7%)
Purpura	0/137 (0%)		0/158 (0%)		1/281 (0.4%)		0/300 (0%)
Vascular disorders
Hypertension	1/137 (0.7%)		0/158 (0%)		0/281 (0%)		0/300 (0%)
Hypotension	0/137 (0%)		0/158 (0%)		0/281 (0%)		1/300 (0.3%)
Other (Not Including Serious) Adverse Events
	Zonisamide (Extension Study 314, NCT00848549)		Carbamazepine (Extension Study 314, NCT00848549)		Zonisamide (Base Study 310, NCT00477295)		Carbamazepine (Base Study 310, NCT00477295)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/137 (8.8%)		10/158 (6.3%)		72/281 (25.6%)		69/300 (23%)
Investigations
Weight Decreased	8/137 (5.8%)		0/158 (0%)		19/281 (6.8%)		0/300 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/137 (0%)		0/158 (0%)		22/281 (7.8%)		5/300 (1.7%)
Nervous system disorders
Headache	6/137 (4.4%)		10/158 (6.3%)		29/281 (10.3%)		37/300 (12.3%)
Somnolence	0/137 (0%)		0/158 (0%)		17/281 (6%)		23/300 (7.7%)
Dizziness	0/137 (0%)		0/158 (0%)		11/281 (3.9%)		23/300 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.