Trial to Assess Lacosamide as the First add-on Anti-epileptic Drug Treatment in Patients With Partial-onset Seizures

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00955357
• Collaborator: (none)
• Enrollment: 461
• Locations: 109
• Arms: 2
• Duration (Months): 48
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of oral Lacosamide as first add on treatment in subjects with uncontrolled partial-onset seizures after prior treatment with a monotherapy Antiepileptic Drug (AED) regimen compared to subjects who have received treatment with at least 2 AEDs.

Condition or Disease	Intervention/Treatment	Phase
Partial Epilepsies	Drug: Lacosamide	Phase 4

Detailed Description

The study consisted of 3 Periods: Period 1: a 1-week Screening Phase, Period 2: a 30-week Treatment Phase (consisting of a 6-week Titration Phase and a 24-week Maintenance Phase), and Period 3: a 3-week Taper/Safety Follow-Up Phase.

Study Design

• Study Type: Interventional
• Actual Enrollment: 461 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Multinational Study of Lacosamide as First Add-On Anti-epileptic Drug (AED) Treatment in Subjects With Partial-Onset Seizures
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: First Add-on Lacosamide added to first adequate monotherapy (no history of Antiepileptic Drug [AED] polytherapy) and epilepsy diagnosis < or = 24 months at Screening.	Drug: Lacosamide; Oral Lacosamide: Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week; Other Names: SPM927 Harkoseride Vimpat
Experimental: Later Add-on Lacosamide added to 1 to 3 Antiepileptic Drugs (AEDs) (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening.	Drug: Lacosamide; Oral Lacosamide: Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week; Other Names: SPM927 Harkoseride Vimpat

Outcome Measures

Primary Outcome Measures

1. The Proportion of Subjects Who Achieved "Seizure-free Status" During the First 12 Weeks of the Maintenance Phase [From Week 7 (end of Week 6) to end of Week 18]

   A subject will be considered seizure-free if the subject completes the first 12 weeks of the Maintenance Phase, reports zero seizures, and has no seizure data missing for any day during the period of time. This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Group 1:

• Subject has a diagnosis of epilepsy with simple partial seizures (motor component) and/or complex partial seizures with or without secondary generalization

• Currently taking adequate monotherapy (defined as a single Antiepileptic Drug (AED) for at least 28 days prior to Screening) and has no history of AED polytherapy. Prior use of rescue medication (short-term intermittent use) is acceptable

• Epilepsy diagnosis should be ≤24 months at the time of the Screening Visit

• The minimum allowed seizure frequency at any time during the 12 weeks prior to the Screening Visit is ≥3 partial-onset seizures

Group 2:

• Subject has a diagnosis of epilepsy with simple partial seizures (motor component) and/or complex partial seizures with or without secondary generalization

• Currently taking 1 to 3 AEDs, and has tried at least 2 prior AED treatment regimens (concurrently or sequentially)

• Epilepsy diagnosis should be ≥5 years at the time of the Screening Visit

• The minimum allowed seizure frequency during the 12 weeks prior to the Screening Visit is ≥1 partial-onset seizure per 28 days

Exclusion Criteria:

• Previous use of Lacosamide

• History of seizure disorder characterized primarily by isolated auras

• History of primary generalized seizures

• History of status epilepticus within last 12-months

• History of cluster seizures during the 12 week period prior to Visit 1

• Nonepileptic events, including pseudoseizures that could be confused with seizure

• Lifetime history of suicide attempt or suicidal ideation in the past 6 months

• Hypersensitivity to any component of Lacosamide

• History of drug or alcohol abuse

• History of an acute or subacutely progressive Central Nervous System (CNS) disease

• Undergone cranial surgery within the last year prior to study entry

• Concomitant treatment of Felbamate or previous Felbamate therapy within the last 6 months

• Prior or concomitant Vigabatrin use

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	103	Irvine	California	United States
2	123	Rancho Mirage	California	United States
3	156	Clearwater	Florida	United States
4	157	Destin	Florida	United States
5	140	Hollywood	Florida	United States
6	161	Ocala	Florida	United States
7	108	Atlanta	Georgia	United States
8	112	Atlanta	Georgia	United States
9	124	Augusta	Georgia	United States
10	115	Macon	Georgia	United States
11	118	Rome	Georgia	United States
12	128	Flossmoor	Illinois	United States
13	130	Des Moines	Iowa	United States
14	102	Bowling Green	Kentucky	United States
15	117	Paducah	Kentucky	United States
16	107	Houma	Louisiana	United States
17	145	Ruston	Louisiana	United States
18	101	Annapolis	Maryland	United States
19	162	Waldorf	Maryland	United States
20	153	Boston	Massachusetts	United States
21	136	Pittsfield	Massachusetts	United States
22	144	Springfield	Massachusetts	United States
23	151	Kansas City	Missouri	United States
24	114	Paterson	New Jersey	United States
25	109	Brooklyn	New York	United States
26	133	Brooklyn	New York	United States
27	127	West Seneca	New York	United States
28	158	Charlotte	North Carolina	United States
29	139	Bismarck	North Dakota	United States
30	134	Akron	Ohio	United States
31	150	Canton	Ohio	United States
32	141	Tulsa	Oklahoma	United States
33	121	Indiana	Pennsylvania	United States
34	120	Columbia	South Carolina	United States
35	149	Orangeburg	South Carolina	United States
36	152	Spartanburg	South Carolina	United States
37	148	Austin	Texas	United States
38	154	Dallas	Texas	United States
39	146	Tomball	Texas	United States
40	119	Fredericksburg	Virginia	United States
41	503	Wien		Austria
42	703	Blagoevrad		Bulgaria
43	706	Pleven		Bulgaria
44	700	Sofia		Bulgaria
45	702	Sofia		Bulgaria
46	704	Sofia		Bulgaria
47	705	Sofia		Bulgaria
48	707	Sofia		Bulgaria
49	708	Sofia		Bulgaria
50	701	Varna		Bulgaria
51	736	Hradec Kralove		Czechia
52	735	Litomerice		Czechia
53	732	Ostrava-Hrabuvka		Czechia
54	733	Ostrava		Czechia
55	737	Praha 11		Czechia
56	734	Trutnov		Czechia
57	930	Aarhus		Denmark
58	400	Helsinki		Finland
59	402	Oulu		Finland
60	401	Tampere		Finland
61	610	Strasbourg		France
62	611	Toulon		France
63	521	Athens		Greece
64	520	Thessaloniki		Greece
65	552	Faenza		Italy
66	546	Gallarate		Italy
67	541	Napoli		Italy
68	559	Pietra Ligure		Italy
69	557	Prato		Italy
70	540	Roma		Italy
71	549	Roma		Italy
72	542	Taranto		Italy
73	547	Torino		Italy
74	551	Trieste		Italy
75	180	Aguascalientes		Mexico
76	183	Chihuahua		Mexico
77	185	Chihuahua		Mexico
78	184	Ciudad Juarez		Mexico
79	189	Guadalajara		Mexico
80	181	Mexico DF		Mexico
81	193	Mexico DF		Mexico
82	195	Mexico DF		Mexico
83	186	Monterrey		Mexico
84	187	Monterrey		Mexico
85	188	Monterrey		Mexico
86	182	Polanco		Mexico
87	815	Bucarest		Romania
88	810	Cluj-napoca		Romania
89	814	Oradea		Romania
90	813	Targu Mures		Romania
91	830	Kazan		Russian Federation
92	831	Kazan		Russian Federation
93	834	Moscow		Russian Federation
94	833	Novosibirsk		Russian Federation
95	598	Terrassa	Barcelona	Spain
96	592	Almeria		Spain
97	597	Bajo Sevilla		Spain
98	590	Barcelona		Spain
99	596	Santiago de Compostela		Spain
100	594	Valencia		Spain
101	599	Valladolid		Spain
102	892	Lausanne		Switzerland
103	713	Adana		Turkey
104	714	Ankara		Turkey
105	710	Eskisehir		Turkey
106	711	Istanbul		Turkey
107	719	Istanbul		Turkey
108	717	Izmir		Turkey
109	718	Trabzon		Turkey

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00955357
• Other Study ID Numbers: SP0954; 2009-011181-28
• First Posted: Aug 10, 2009
• Last Update Posted: Jul 17, 2018
• Last Verified: Jul 1, 2017

• Keywords provided by UCB Pharma: Epilepsy Treatment; Anti-epileptic drugs; Seizures; Vimpat
• Additional relevant MeSH terms: Epilepsy; Seizures; Epilepsies, Partial; Lacosamide

Study Results

Participant Flow

Recruitment Details	An estimated 656 subjects were to be enrolled in the study at approximately 130 sites in the US, Europe, and the rest of the world.
Pre-assignment Detail	Overall 461 subjects were enrolled. The Participant Flow refers to the Safety Set (SS) which was defined as all enrolled subjects who took at least 1 dose of Lacosamide. Reasons for discontinuation were only calculated for the SS. 456 subjects were included in the Safety Set.

Arm/Group Title	First Add-on	Later Add-on
Arm/Group Description	Lacosamide added to first adequate monotherapy (no history of Anti-Epileptic Drug [AED] polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Lacosamide added to 1 to 3 Anti-Epileptic Drugs (AEDs) (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
Period Title: Titration Phase
STARTED	96	360
COMPLETED	80	294
NOT COMPLETED	16	66
Period Title: Titration Phase
STARTED	80	294
COMPLETED	68	249
NOT COMPLETED	12	45

Baseline Characteristics

Arm/Group Title	First Add-on	Later-Add-on	Total
Arm/Group Description	Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Total of all reporting groups
Overall Participants	96	360	456
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	37.5	38.0	38.0
Age (Count of Participants)
<=18 years	4 4.2%	7 1.9%	11 2.4%
Between 18 and 65 years	82 85.4%	349 96.9%	431 94.5%
>=65 years	10 10.4%	4 1.1%	14 3.1%
Sex: Female, Male (Count of Participants)
Female	53 55.2%	180 50%	233 51.1%
Male	43 44.8%	180 50%	223 48.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	11 11.5%	6 1.7%	17 3.7%
Asian	0 0%	12 3.3%	12 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1%	19 5.3%	20 4.4%
White	79 82.3%	278 77.2%	357 78.3%
More than one race	5 5.2%	45 12.5%	50 11%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 25%	99 27.5%	123 27%
Not Hispanic or Latino	72 75%	261 72.5%	333 73%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kilogram) [Median (Full Range) ]
Median (Full Range) [kilogram]	71.8	73.0	73.0
Height (centimeter) [Median (Full Range) ]
Median (Full Range) [centimeter]	166.5	167.6	167.6
BMI (kilogram per m^2) [Median (Full Range) ]
Median (Full Range) [kilogram per m^2]	25.3	25.5	25.4

Outcome Measures

1. Primary Outcome

Title	The Proportion of Subjects Who Achieved "Seizure-free Status" During the First 12 Weeks of the Maintenance Phase
Description	A subject will be considered seizure-free if the subject completes the first 12 weeks of the Maintenance Phase, reports zero seizures, and has no seizure data missing for any day during the period of time. This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.
Time Frame	From Week 7 (end of Week 6) to end of Week 18

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Completer Set (CS) which includes all subjects who were enrolled, received at least one dose of Lacosamide and completed the first 12 weeks of the Maintenance Phase.

Arm/Group Title	First Add-on	Later Add-on
Arm/Group Description	Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
Measure Participants	72	261
Number [percentage of subjects]	37.5	14.9

Adverse Events

Time Frame	Treatment Emergent Adverse Events were collected from Screening (Week -1) until the end of the study ( up to Week 33).
Adverse Event Reporting Description	Treatment Emergent Adverse Events started on/after the date of first dose and within 30 days of the date of last dose.
Arm/Group Title	First Add-on		Later Add-on
Arm/Group Description	Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week		Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
All Cause Mortality
	First Add-on		Later Add-on
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	First Add-on		Later Add-on
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/96 (8.3%)		19/360 (5.3%)
Blood and lymphatic system disorders
Agranulocytosis	0/96 (0%)	0	1/360 (0.3%)	1
Cardiac disorders
Angina pectoris	1/96 (1%)	1	0/360 (0%)	0
Eye disorders
Diplopia	0/96 (0%)	0	1/360 (0.3%)	1
General disorders
Pyrexia	0/96 (0%)	0	2/360 (0.6%)	2
Chest discomfort	0/96 (0%)	0	1/360 (0.3%)	1
Infections and infestations
Pneumonia	1/96 (1%)	1	0/360 (0%)	0
Tooth abscess	0/96 (0%)	0	1/360 (0.3%)	1
Urinary tract infection	1/96 (1%)	1	0/360 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/96 (0%)	0	1/360 (0.3%)	1
Femoral neck fracture	1/96 (1%)	1	0/360 (0%)	0
Hip fracture	1/96 (1%)	1	0/360 (0%)	0
Humerus fracture	1/96 (1%)	1	0/360 (0%)	0
Joint dislocation	0/96 (0%)	0	1/360 (0.3%)	1
Subdural haematoma	1/96 (1%)	1	0/360 (0%)	0
Investigations
Electrocardiogram ST segment elevation	0/96 (0%)	0	1/360 (0.3%)	1
Metabolism and nutrition disorders
Hypochloraemia	0/96 (0%)	0	1/360 (0.3%)	1
Hyponatraemia	0/96 (0%)	0	1/360 (0.3%)	1
Nervous system disorders
Convulsion	2/96 (2.1%)	2	2/360 (0.6%)	2
Dizziness	0/96 (0%)	0	2/360 (0.6%)	2
Complex partial seizures	0/96 (0%)	0	1/360 (0.3%)	1
Coordination abnormal	0/96 (0%)	0	1/360 (0.3%)	1
Dysarthria	0/96 (0%)	0	1/360 (0.3%)	1
Dyskinesia	0/96 (0%)	0	1/360 (0.3%)	1
Epilepsy	0/96 (0%)	0	1/360 (0.3%)	1
Grand mal convulsion	0/96 (0%)	0	1/360 (0.3%)	1
Headache	0/96 (0%)	0	1/360 (0.3%)	1
Lacunar infarction	0/96 (0%)	0	1/360 (0.3%)	1
Partial seizures with secondary generalisation	0/96 (0%)	0	1/360 (0.3%)	1
Psychiatric disorders
Panic attack	0/96 (0%)	0	1/360 (0.3%)	1
Suicide attempt	1/96 (1%)	1	0/360 (0%)	0
Surgical and medical procedures
Abortion induced	1/96 (1%)	1	1/360 (0.3%)	1
Other (Not Including Serious) Adverse Events
	First Add-on		Later Add-on
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/96 (55.2%)		212/360 (58.9%)
Ear and labyrinth disorders
Vertigo	9/96 (9.4%)	11	22/360 (6.1%)	22
Eye disorders
Vision blurred	2/96 (2.1%)	3	24/360 (6.7%)	28
Diplopia	7/96 (7.3%)	7	17/360 (4.7%)	17
Gastrointestinal disorders
Nausea	8/96 (8.3%)	8	24/360 (6.7%)	27
Infections and infestations
Influenza	5/96 (5.2%)	5	4/360 (1.1%)	4
Nervous system disorders
Dizziness	30/96 (31.3%)	37	119/360 (33.1%)	159
Somnolence	6/96 (6.3%)	8	54/360 (15%)	65
Headache	13/96 (13.5%)	19	41/360 (11.4%)	57
Tremor	3/96 (3.1%)	3	22/360 (6.1%)	23
Psychiatric disorders
Anxiety	6/96 (6.3%)	6	4/360 (1.1%)	4

Limitations/Caveats

This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.