Marigold: Study of Adjunctive Ganaxolone Treatment in Children and Young Adults With CDKL5 Deficiency Disorder

• Sponsor: Marinus Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03572933
• Collaborator: (none)
• Enrollment: 101
• Locations: 36
• Arms: 2
• Actual Duration (Months): 34.9
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A clinical study to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in children and young adults with genetically confirmed CDKL5 gene mutation.

Condition or Disease	Intervention/Treatment	Phase
CDKL5 Deficiency Disorder	Drug: ganaxolone; Drug: Placebo	Phase 3

Detailed Description

The Marigold Study is a global, double-blind, placebo-controlled, Phase 3 clinical trial that will enroll approximately 70 patients between the ages of 2 and 21 with a confirmed disease-related CDKL5 gene variant. Patients will undergo a baseline period before being randomized to receive, in addition to their existing anti-seizure treatment, either ganaxolone or placebo for 17 weeks. Following the treatment period, all patients that meet certain eligibility requirements will have the opportunity to receive ganaxolone in the open label phase of the study. The study's primary efficacy endpoint is percent reduction in seizures. Secondary outcome measures will include non-seizure-related endpoints to capture certain behavioral and sleep disturbances that have been seen in previous clinical studies with ganaxolone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of careThe double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Children and Young Adults With Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) Followed by Long-term Open-label Treatment
• Actual Study Start Date: Jun 30, 2018
• Actual Primary Completion Date: Jul 31, 2020
• Actual Study Completion Date: May 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ganaxolone ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks	Drug: ganaxolone; active drug
Placebo Comparator: Placebo placebo suspension 3x's /day for 17 weeks	Drug: Placebo; inactive; Other Names: Placebo (for ganaxolone)

Outcome Measures

Primary Outcome Measures

1. Summary of 28-day Seizure Frequency for Major Motor Seizure Types [End of the double-blind 17 week treatment period]

   Summary of 28-day seizure frequency for Major Motor Seizure Types during the double-blind treatment period relative to the 6-week prospective baseline period Note: Summaries are based on the sum of the individual seizures, the countable seizures, and the clusters with uncountable seizures (each cluster with uncountable seizures counts as 1 seizure). Within the baseline and post baseline intervals, 28-day seizure frequency was calculated as the total number of seizures in the interval divided by the number of days with available seizure data in the interval, multiplied by 28.

Secondary Outcome Measures

1. Caregiver Global Impression of Change in Attention [End of the double-blind 17 week treatment period]

   Caregiver global impression of change in attention during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives

2. Caregiver Global Impression of Change in Target Behavior [End of the double-blind 17 week treatment period]

   Caregiver global impression of change in target behavior during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives.

3. Clinical Global Impression of Improvement - Parent/Caregiver [End of the double-blind 17 week treatment period]

   Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses.

4. Clinical Global Impression of Improvement - Clinician [[Time Frame: End of the double-blind 17 week treatment period]]

   Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo

5. Percentage of Seizure-free Days for Major Motor Seizure Types [End of the double-blind 17 week treatment period]

   Percentage of Seizure-free Days for Major Motor Seizure types during the double-blind treatment period of ganaxolone compared to placebo. The major motor seizure types include bilateral tonic (sustained motor activity = 3 seconds), generalized tonic-clonic, atonic/drop, bilateral clonic, and focal to bilateral tonic-clonic.

6. Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types [End of the double-blind 17 week treatment period]

   Arithmetic change in longest seizure free interval, based on primary seizure types during the double-blind treatment period of ganaxolone compared to placebo

7. Caregiver Global Impression of Change in Seizure Intensity and Duration [End of the double-blind 17 week treatment period]

   Caregiver global impression of change in seizure intensity and duration during the double-blind treatment period of ganaxolone compared to placebo. CGI-C is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Genetically confirmed CDKL5 gene mutation, seizure onset by 1 year of age and lack of independent ambulation by 2 years of age

• Failure to control seizures despite 2 or more anti-seizure medications

• At least 16 seizures per 28 days of primary seizure types

• On a stable regimen of 0-4 anti-seizure medications (Vagus nerve stimulator, ketogenic diet, and modified Atkins diet do not count towards this limit)

• Additional Inclusion Criteria apply and can be discussed with study team

Exclusion Criteria:

• Previous exposure to ganaxolone

• West Syndrome with hypsarrhythmia pattern on EEG or seizures predominantly of Infantile Spasms type

• Use of adrenocorticotropic hormone (ACTH), prednisone or other glucocorticoid or use of moderate or strong inducers or inhibitors of CYP3A4/5/7 are prohibited

• Use of tetrahydrocannabinol (THC) or cannabidiol (CBD) is prohibited during the double-blind phase, unless patient has a prescription of Epidiolex®

• Exposure to any other investigational drug within 30 days or fewer than 5 half-lives prior to screening

• Plasma allopregnanolone-sulfate (Allo-S) levels greater than or equal to 6.0 ng/ml at screening visit

• Additional Exclusion Criteria apply and can be discussed with study team

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marinus Research Site	Phoenix	Arizona	United States	85016
2	Marinus Research Site	Los Angeles	California	United States	90095-1742
3	Marinus Research Site	Aurora	Colorado	United States	80045
4	Marinus Research Site	Gulf Breeze	Florida	United States	32561
5	Marinus Research Site	Orlando	Florida	United States	32819
6	Marinus Research Site	Norcross	Georgia	United States	30093
7	Marinus Research Site	Chicago	Illinois	United States	60612-3852
8	Marinus Research Site	Iowa City	Iowa	United States	52242
9	Marinus Research Site	Boston	Massachusetts	United States	02115
10	Marinus Research Site	Rochester	Minnesota	United States	55905
11	Marinus Research Site	Saint Louis	Missouri	United States	63130
12	Marinus Research Site	Livingston	New Jersey	United States	07039
13	Marinus Research Site	Cleveland	Ohio	United States	44195
14	Marinus Research Site	Philadelphia	Pennsylvania	United States	19104-4318
15	Marinus Research Site	Pittsburgh	Pennsylvania	United States	15224
16	Marinus Research Site	Fort Worth	Texas	United States	76104
17	Marinus Research Site	Houston	Texas	United States	77030
18	Marinus Research Site	Brisbane	Queensland	Australia	4101
19	Marinus Research Site	Heidelberg	Victoria	Australia	3084
20	Marinus Research Site	Melbourne	Victoria	Australia	3168
21	Marinus Research Site	Paris		France
22	Marinus Research Site	Ramat Gan		Israel
23	Marinus Research Site	Firenze		Italy
24	Marinus Research Site	Milano		Italy
25	Marinus Research Site	Pavia		Italy
26	Marinus Research Site	Roma		Italy
27	Marinus Research Site	Verona		Italy
28	Marinus Research Site	Bydgoszcz		Poland
29	Marinus Research Site	Kraków		Poland
30	Marinus Research Site	Moscow		Russian Federation
31	Marinus Research Site	Nizhniy Novgorod		Russian Federation
32	Marinus Research Site	Novosibirsk		Russian Federation
33	Marinus Research Site	Birmingham		United Kingdom
34	Marinus Research Site	Bristol		United Kingdom
35	Marinus Research Facility	Glasgow		United Kingdom
36	Marinus Research Site	London		United Kingdom

Sponsors and Collaborators

• Marinus Pharmaceuticals

Investigators

• Study Director: Joseph Hulihan, MD, Marinus Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - May 27, 2020
• Statistical Analysis Plan - Aug 22, 2019

More Information

Publications

None provided.

• Responsible Party: Marinus Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03572933
• Other Study ID Numbers: 1042-CDD-3001; 2018-001180-23
• First Posted: Jun 28, 2018
• Last Update Posted: Jul 26, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Marinus Pharmaceuticals: refractory seizures; genetic pediatric encephalopathies; epilepsy in children; seizure disorder
• Additional relevant MeSH terms: Disease; Pregnanolone; Ganaxolone

Study Results

Participant Flow

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Period Title: Overall Study
STARTED	51	50
COMPLETED	47	48
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Placebo	Ganaxolone	Total
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug	Total of all reporting groups
Overall Participants	51	50	101
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.73 (4.382)	6.78 (4.705)	7.26 (4.547)
Sex: Female, Male (Count of Participants)
Female	41 80.4%	39 78%	80 79.2%
Male	10 19.6%	11 22%	21 20.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 11.8%	4 8%	10 9.9%
Not Hispanic or Latino	43 84.3%	44 88%	87 86.1%
Unknown or Not Reported	2 3.9%	2 4%	4 4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 5.9%	2 4%	5 5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	47 92.2%	46 92%	93 92.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2%	2 4%	3 3%
Region of Enrollment (participants) [Number]
United States	24 47.1%	18 36%	42 41.6%
Poland	5 9.8%	5 10%	10 9.9%
Italy	6 11.8%	9 18%	15 14.9%
United Kingdom	3 5.9%	4 8%	7 6.9%
Israel	1 2%	0 0%	1 1%
Australia	2 3.9%	4 8%	6 5.9%
France	3 5.9%	3 6%	6 5.9%
Russia	7 13.7%	7 14%	14 13.9%

Outcome Measures

1. Primary Outcome

Title	Summary of 28-day Seizure Frequency for Major Motor Seizure Types
Description	Summary of 28-day seizure frequency for Major Motor Seizure Types during the double-blind treatment period relative to the 6-week prospective baseline period Note: Summaries are based on the sum of the individual seizures, the countable seizures, and the clusters with uncountable seizures (each cluster with uncountable seizures counts as 1 seizure). Within the baseline and post baseline intervals, 28-day seizure frequency was calculated as the total number of seizures in the interval divided by the number of days with available seizure data in the interval, multiplied by 28.
Time Frame	End of the double-blind 17 week treatment period

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	51	49
Baseline (Median)	49.17	54.00
17 week-post baseline phase (Median)	55.50	45.03

2. Secondary Outcome

Title	Caregiver Global Impression of Change in Attention
Description	Caregiver global impression of change in attention during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives
Time Frame	End of the double-blind 17 week treatment period

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	51	50
Very Much Improved - Visit 5 (End of Week 17)	1 2%	1 2%
Much Improved - Visit 5 (End of Week 17)	7 13.7%	2 4%
Minimally Improved - Visit 5 (End of Week 17)	14 27.5%	21 42%
No Change - Visit 5 (End of Week 17)	23 45.1%	18 36%
Minimally Worse - Visit 5 (End of Week 17)	1 2%	1 2%
Much Worse - Visit 5 (End of Week 17)	1 2%	1 2%
Very Much Worse - Visit 5 (End of Week 17)	0 0%	1 2%

3. Secondary Outcome

Title	Caregiver Global Impression of Change in Target Behavior
Description	Caregiver global impression of change in target behavior during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives.
Time Frame	End of the double-blind 17 week treatment period

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	51	50
Very Much Improved - Visit 5 (End of Week 17)	0 0%	0 0%
Much Improved - Visit 5 (End of Week 17)	6 11.8%	4 8%
Minimally Improved - Visit 5 (End of Week 17)	14 27.5%	20 40%
No Change - Visit 5 (End of Week 17)	22 43.1%	19 38%
Minimally Worse - Visit 5 (End of Week 17)	1 2%	2 4%
Much Worse - Visit 5 (End of Week 17)	2 3.9%	0 0%
Very Much Worse - Visit 5 (End of Week 17)	1 2%	0 0%

4. Secondary Outcome

Title	Clinical Global Impression of Improvement - Parent/Caregiver
Description	Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses.
Time Frame	End of the double-blind 17 week treatment period

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	48	48
Very Much Improved - Visit 5 (End of Week 17) - Parent/Caregiver	1 2%	0 0%
Much Improved - Visit 5 (End of Week 17) - Parent/Caregiver	7 13.7%	13 26%
Minimally Improved - Visit 5 (End of Week 17) - Parent/Caregiver	13 25.5%	17 34%
No Change - Visit 5 (End of Week 17) - Parent/Caregiver	22 43.1%	14 28%
Minimally Worse - Visit 5 (End of Week 17) - Parent/Caregiver	4 7.8%	2 4%
Much Worse - Visit 5 (End of Week 17) - Parent/Caregiver	1 2%	2 4%
Very Much Worse - Visit 5 (End of Week 17) - Parent/Caregiver	0 0%	0 0%

5. Secondary Outcome

Title	Clinical Global Impression of Improvement - Clinician
Description	Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo
Time Frame	[Time Frame: End of the double-blind 17 week treatment period]

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	48	48
Very Much Improved - Visit 5 (End of Week 17) - Clinician	0 0%	0 0%
Much Improved - Visit 5 (End of Week 17) - Clinician	7 13.7%	7 14%
Minimally Improved - Visit 5 (End of Week 17) - Clinician	13 25.5%	19 38%
No Change - Visit 5 (End of Week 17) - Clinician	19 37.3%	16 32%
Minimally Worse - Visit 5 (End of Week 17) - Clinician	9 17.6%	2 4%
Much Worse - Visit 5 (End of Week 17) - Clinician	0 0%	3 6%
Very Much Worse - Visit 5 (End of Week 17) - Clinician	0 0%	1 2%

6. Secondary Outcome

Title	Percentage of Seizure-free Days for Major Motor Seizure Types
Description	Percentage of Seizure-free Days for Major Motor Seizure types during the double-blind treatment period of ganaxolone compared to placebo. The major motor seizure types include bilateral tonic (sustained motor activity = 3 seconds), generalized tonic-clonic, atonic/drop, bilateral clonic, and focal to bilateral tonic-clonic.
Time Frame	End of the double-blind 17 week treatment period

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	51	50
Baseline	30.32 (27.070)	22.57 (25.761)
17-week-Post-Baseline Phase	36.17 (30.932)	32.29 (30.615)
Arithmetic Change from Baseline	5.86 (15.350)	9.62 (21.364)

7. Secondary Outcome

Title	Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types
Description	Arithmetic change in longest seizure free interval, based on primary seizure types during the double-blind treatment period of ganaxolone compared to placebo
Time Frame	End of the double-blind 17 week treatment period

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	51	49
Mean (Standard Deviation) [days]	-4.63 (14.867)	-0.02 (9.376)

8. Secondary Outcome

Title	Caregiver Global Impression of Change in Seizure Intensity and Duration
Description	Caregiver global impression of change in seizure intensity and duration during the double-blind treatment period of ganaxolone compared to placebo. CGI-C is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.
Time Frame	End of the double-blind 17 week treatment period

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Placebo	Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
Measure Participants	51	50
Very Much Improved - Visit 5 (End of Week 17)	1 2%	2 4%
Much Improved - Visit 5 (End of Week 17)	5 9.8%	15 30%
Minimally Improved - Visit 5 (End of Week 17)	11 21.6%	11 22%
No Change - Visit 5 (End of Week 17)	21 41.2%	10 20%
4Minimally Worse - Visit 5 (End of Week 17)	5 9.8%	3 6%
Much Worse - Visit 5 (End of Week 17)	4 7.8%	2 4%
Very Much Worse - Visit 5 (End of Week 17)	0 0%	2 4%

Adverse Events

Time Frame	Screening through 17-week Double-blind Phase
Arm/Group Title	Placebo		Ganaxolone
Arm/Group Description	placebo suspension 3x's /day for 17 weeks Placebo: inactive		ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug
All Cause Mortality
	Placebo		Ganaxolone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)
Serious Adverse Events
	Placebo		Ganaxolone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/51 (9.8%)		6/50 (12%)
Gastrointestinal disorders
Faecaloma	1/51 (2%)	1	0/50 (0%)	0
Infections and infestations
Bronchitis	0/51 (0%)	0	1/50 (2%)	1
Rhinovirus Infection	0/51 (0%)	0	1/50 (2%)	1
Urinary Tract Infection	0/51 (0%)	0	1/50 (2%)	1
Pneumonia Mycoplasmal	1/51 (2%)	1	0/50 (0%)	0
Pneumonia Viral	1/51 (2%)	1	0/50 (0%)	0
Respiratory Syncytial Virus Bronchiolitis	1/51 (2%)	1	0/50 (0%)	0
Investigations
Oxygen Saturation Decreased	0/51 (0%)	0	1/50 (2%)	1
Metabolism and nutrition disorders
Food Refusal	0/51 (0%)	0	1/50 (2%)	1
Nervous system disorders
Hypotonia	1/51 (2%)	1	0/50 (0%)	0
Seizure	1/51 (2%)	1	0/50 (0%)	0
Unresponsive to Stimuli	1/51 (2%)	2	0/50 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration	0/51 (0%)	0	1/50 (2%)	1
Hypoxia	1/51 (2%)	2	0/50 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Ganaxolone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/51 (88.2%)		43/50 (86%)
Gastrointestinal disorders
Vomiting	10/51 (19.6%)	12	5/50 (10%)	6
Constipation	3/51 (5.9%)	3	3/50 (6%)	3
Salivary Hypersecretion	1/51 (2%)	1	3/50 (6%)	3
Diarrhoea	4/51 (7.8%)	5	1/50 (2%)	1
Abdominal Pain	2/51 (3.9%)	2	0/50 (0%)	0
Gastrooesophageal Reflux Disease	3/51 (5.9%)	3	0/50 (0%)	0
General disorders
Pyrexia	4/51 (7.8%)	5	9/50 (18%)	10
Gait Disturbance	1/51 (2%)	1	2/50 (4%)	2
Immune system disorders
Seasonal Allergy	0/51 (0%)	0	3/50 (6%)	3
Infections and infestations
Upper Respiratory Tract Infection	3/51 (5.9%)	3	5/50 (10%)	6
Bronchitis	0/51 (0%)	0	2/50 (4%)	2
Ear Infection	3/51 (5.9%)	3	2/50 (4%)	2
Influenza	1/51 (2%)	1	2/50 (4%)	2
Rhinitis	4/51 (7.8%)	5	2/50 (4%)	4
Respiratory Tract Infection Viral	3/51 (5.9%)	3	1/50 (2%)	1
Urinary Tract Infection	3/51 (5.9%)	3	1/50 (2%)	2
Nasopharyngitis	5/51 (9.8%)	5	0/50 (0%)	0
Sinusitis	2/51 (3.9%)	2	0/50 (0%)	0
Varicella	2/51 (3.9%)	3	0/50 (0%)	0
Investigations
Body Temperature Increased	2/51 (3.9%)	3	0/50 (0%)	0
Nervous system disorders
Somnolence	8/51 (15.7%)	8	18/50 (36%)	20
Seizure	9/51 (17.6%)	12	7/50 (14%)	8
Sedation	2/51 (3.9%)	2	3/50 (6%)	3
Hypersomnia	0/51 (0%)	0	2/50 (4%)	2
Lethargy	2/51 (3.9%)	2	2/50 (4%)	2
Hyperaesthesia	2/51 (3.9%)	2	0/50 (0%)	0
Psychiatric disorders
Irritability	2/51 (3.9%)	2	2/50 (4%)	2
Respiratory, thoracic and mediastinal disorders
Nasal Congestion	1/51 (2%)	1	2/50 (4%)	2
Rhinorrhoea	2/51 (3.9%)	2	1/50 (2%)	1
Cough	3/51 (5.9%)	3	0/50 (0%)	0
Insomnia	2/51 (3.9%)	3	2/50 (4%)	2
Skin and subcutaneous tissue disorders
Rash	4/51 (7.8%)	4	3/50 (6%)	3
Alopecia	2/51 (3.9%)	2	0/50 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If the study is part of a multicenter study, the first publication of the study results shall be made by the sponsor in conjunction with the sponsor's presentation of a joint, multicenter publication of the compiled and analyzed study results.