Long-Term Study of Atomoxetine in Children With Attention-Deficit/Hyperactivity Disorder (AD/HD)

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00191386
• Collaborator: (none)
• Enrollment: 228
• Locations: 24
• Arm: 1
• Duration (Months): 51
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study is long-term extension study to evaluate long-term safety and efficacy of Atomoxetine in Japanese pediatric patients with Attention-Deficit/Hyperactivity Disorder (AD/HD).

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: Atomoxetine hydrochloride	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 228 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long-Term Extension, Open-Label Study of Atomoxetine Hydrochloride in Child Outpatients With Attention-Deficit/Hyperactivity Disorder
• Study Start Date: May 1, 2005
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atomoxetine 0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years	Drug: Atomoxetine hydrochloride; 0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years; Other Names: LY139603 Strattera

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events for Long Term Safety and Tolerability [Baseline through 4 years]

   Details on the actual adverse events are presented in the Reported Adverse Events Section.

Secondary Outcome Measures

1. Change From Baseline at Various Timepoints in Attention Deficit Hyperactivity Disorder Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered and Scored (ADHDRS-IV-J:I) Total Score [Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years]

   Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54.

2. Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S) [Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years]

   Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).

3. Cytochrome P450 2D6 (CYP2D6) Phenotype Status [Over 1 year]

   Participants were categorized as either extensive metabolizers (EM) or poor metabolizers (PM). CYP2D6 is the primary atomoxetine metabolizing enzyme. The CYP2D6 genotype were analysed by testing the *2, *3, *4, *5, *6, *7, *8, and *10 alleles. Metabolizer status was determined by focusing on the normal(wild type, *2), decreased(*10), and defective allele(*3, *4, *5, *6, *7, or *8). PM were assigned to the patients had two defective alleles in any combination of *3, *4, *5, *6, *7, or *8 alleles. EM was all except for PM.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who met all of the disease diagnostic and study criteria at Visit 2 of previous placebo-controlled study, completed the study

• Patients wish to enter into this study

Exclusion Criteria:

• Patients whose families anticipate a move outside the geographic range of the investigative site, or who plan extended travel inconsistent with the recommended visit interval

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Aichi		Japan
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chiba		Japan
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukui		Japan
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka		Japan
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hokkaido		Japan
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hyogo		Japan
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ibaraki		Japan
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ishikawa		Japan
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kanagawa		Japan
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kumamoto		Japan
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mie		Japan
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Miyagi		Japan
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagano		Japan
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nara		Japan
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Okayama		Japan
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka		Japan
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saga		Japan
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shiga		Japan
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shizuoka		Japan
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tochigi		Japan
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokushima		Japan
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo		Japan
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toyama		Japan
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wakayama		Japan

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00191386
• Other Study ID Numbers: 9315; B4Z-JE-LYDA
• First Posted: Sep 19, 2005
• Last Update Posted: Dec 28, 2010
• Last Verified: Dec 1, 2010

• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride

Study Results

Participant Flow

Recruitment Details	This ongoing study is being conducted as a follow-up investigation of ADHD pediatric patients who completed Study LYBC (NCT00191295).

Arm/Group Title	Atomoxetine
Arm/Group Description	0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
Period Title: Overall Study
STARTED	228
6 Months	183
12 Months	149
2 Years	105
3 Years	65
COMPLETED	68
NOT COMPLETED	160

Baseline Characteristics

Arm/Group Title	Atomoxetine
Arm/Group Description	0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
Overall Participants	228
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.69 (2.48)
Sex: Female, Male (Count of Participants)
Female	33 14.5%
Male	195 85.5%
Race/Ethnicity, Customized (Number) [Number]
East Asian	228 100%
Region of Enrollment (participants) [Number]
Japan	228 100%
ADHD Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered/Scored (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	22.23 (10.42)
Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S) (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	4.00 (1.04)
Mean Age at Onset of Attention Deficit Hyperactivity Disorder (ADHD) (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	3.93 (1.57)
Age at Onset of ADHD (Number) [Number]
0 Years	1 0.4%
1 Years	17 7.5%
2 Years	25 11%
3 Years	49 21.5%
4 Years	45 19.7%
5 Years	47 20.6%
6 Years	40 17.5%
7 Years	4 1.8%
Duration of ADHD (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	6.25 (2.85)
Duration of ADHD (Number) [Number]
1 Years	6 2.6%
2 Years	8 3.5%
3 Years	30 13.2%
4 Years	24 10.5%
5 Years	32 14%
6 Years	26 11.4%
7 Years	31 13.6%
8 Years	21 9.2%
9 Years	22 9.6%
10 Years	11 4.8%
11 Years	4 1.8%
12 Years	7 3.1%
13 Years	3 1.3%
14 Years	3 1.3%
Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-PL (Participants with Disorder Presently) [Number]
Oppositional Defiant Disorder	32 14%
Conduct Disorder	2 0.9%
Specific Phobia	3 1.3%
Generalized Anxiety Disorder	1 0.4%
Obsessive Compulsive Disorder	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events for Long Term Safety and Tolerability
Description	Details on the actual adverse events are presented in the Reported Adverse Events Section.
Time Frame	Baseline through 4 years

Outcome Measure Data

Analysis Population Description

All patients who took at least one dose of study medication were included in the analyses of safety data.

Arm/Group Title	Atomoxetine
Arm/Group Description	0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
Measure Participants	228
Serious Adverse Events	6 2.6%
All Other Nonserious Adverse Events	222 97.4%

2. Secondary Outcome

Title	Change From Baseline at Various Timepoints in Attention Deficit Hyperactivity Disorder Rating Scale-IV-Translated in Japanese Parent Version: Investigator Administered and Scored (ADHDRS-IV-J:I) Total Score
Description	Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54.
Time Frame	Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years

Outcome Measure Data

Analysis Population Description

Full Analysis Set: Participants who met Study LYBC criteria, took 1 dose of drug, had a baseline/post-baseline measurement. Changes from baseline used LOCF approach. Baseline was the last non-missing measurement before taking atomoxetine (either LYDA Week 0 or LYBC Week 2). Endpoint was the last non-missing measurement in each assessment period.

Arm/Group Title	Atomoxetine
Arm/Group Description	0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
Measure Participants	228
Total Score 6 Months (n=228)	-14.1 (9.3)
Total Score 12 Months (n=178)	-16.0 (9.2)
Total Score 2 Years (n=143)	-17.7 (9.4)
Total Score 3 Years (n=105)	-20.0 (9.2)
Total Score 4 Years (n=62)	-20.1 (10.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for Total Score 6 Months
	Method	Paired t-test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for Total Score 12 Months
	Method	Paired t-test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for Total Score 2 Years.
	Method	Paired t-test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for Total Score 3 Years.
	Method	Paired t-test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for Total Score 4 Years.
	Method	Paired t-test
	Comments

3. Secondary Outcome

Title	Change From Baseline at Various Timepoints in the Clinical Global Impressions-Attention Deficit Hyperactivity Disorder-Severity (CGI-ADHD-S)
Description	Measures severity of the participant's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients).
Time Frame	Baseline, 6 Months, 12 Months, 2 Years, 3 Years, 4 Years

Outcome Measure Data

Analysis Population Description

Full Analysis Set: Participants who met Study LYBC criteria, took 1 dose of drug, had a baseline/post-baseline measurement. Changes from baseline used LOCF approach. Baseline was the last non-missing measurement before taking atomoxetine (either LYDA Week 0 or LYBC Week 2). Endpoint was the last non-missing measurement in each assessment period.

Arm/Group Title	Atomoxetine
Arm/Group Description	0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
Measure Participants	228
6 Months	-1.1 (1.1)
12 Months	-1.3 (1.1)
2 Years	-1.4 (1.0)
3 Years	-1.6 (1.0)
4 Years	-1.8 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for 6 Months.
	Method	Paired t-test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for 12 Months.
	Method	Paired t-test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for 2 Years.
	Method	Paired t-test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for 3 Years.
	Method	Paired t-test
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Atomoxetine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-Value for 4 Years.
	Method	Paired t-test
	Comments

4. Secondary Outcome

Title	Cytochrome P450 2D6 (CYP2D6) Phenotype Status
Description	Participants were categorized as either extensive metabolizers (EM) or poor metabolizers (PM). CYP2D6 is the primary atomoxetine metabolizing enzyme. The CYP2D6 genotype were analysed by testing the *2, *3, *4, *5, *6, *7, *8, and *10 alleles. Metabolizer status was determined by focusing on the normal(wild type, *2), decreased(*10), and defective allele(*3, *4, *5, *6, *7, or *8). PM were assigned to the patients had two defective alleles in any combination of *3, *4, *5, *6, *7, or *8 alleles. EM was all except for PM.
Time Frame	Over 1 year

Outcome Measure Data

Analysis Population Description

Full Analysis Set: Participants who met Study LYBC criteria, took 1 dose of drug, had a baseline/post-baseline measurement. Changes from baseline used LOCF approach. Baseline was the last non-missing measurement before taking atomoxetine (either LYDA Week 0 or LYBC Week 2). Endpoint was the last non-missing measurement in each assessment period.

Arm/Group Title	Atomoxetine
Arm/Group Description	0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
Measure Participants	228
Extensive Metabolizer	225 98.7%
Poor Metabolizer	3 1.3%

Adverse Events

Arm/Group Title	Atomoxetine
Arm/Group Description	0.5 milligrams per kilogram (mg/kg) twice daily (BID), orally (PO) titrated to 1.2 mg/kg BID, PO over 2 weeks then 1.2 to 1.8 mg/kg BID, PO for 6 months and up to 4 years
All Cause Mortality
	Atomoxetine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Atomoxetine
	Affected / at Risk (%)	# Events
Total	6/228 (2.6%)
Endocrine disorders
Thyroiditis	1/228 (0.4%)	1
Hepatobiliary disorders
Hepatic function abnormal	1/228 (0.4%)	1
Infections and infestations
Pneumonia mycoplasmal	1/228 (0.4%)	1
Injury, poisoning and procedural complications
Eye injury	1/228 (0.4%)	1
Psychiatric disorders
Schizophrenia	1/228 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/228 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Atomoxetine
	Affected / at Risk (%)	# Events
Total	222/228 (97.4%)
Eye disorders
Conjunctivitis allergic	13/228 (5.7%)	17
Myopia	12/228 (5.3%)	13
Gastrointestinal disorders
Abdominal pain	53/228 (23.2%)	106
Constipation	17/228 (7.5%)	25
Dental caries	23/228 (10.1%)	24
Diarrhoea	42/228 (18.4%)	58
Nausea	28/228 (12.3%)	47
Stomatitis	20/228 (8.8%)	27
Toothache	12/228 (5.3%)	12
Vomiting	29/228 (12.7%)	45
General disorders
Malaise	14/228 (6.1%)	20
Pyrexia	34/228 (14.9%)	43
Infections and infestations
Bronchitis	23/228 (10.1%)	39
Gastroenteritis	36/228 (15.8%)	53
Gastroenteritis viral	18/228 (7.9%)	25
Impetigo	15/228 (6.6%)	17
Influenza	55/228 (24.1%)	62
Nasopharyngitis	127/228 (55.7%)	420
Otitis media	12/228 (5.3%)	14
Pharyngitis	26/228 (11.4%)	46
Rhinitis	17/228 (7.5%)	31
Injury, poisoning and procedural complications
Arthropod sting	18/228 (7.9%)	41
Contusion	30/228 (13.2%)	51
Excoriation	17/228 (7.5%)	30
Fall	18/228 (7.9%)	26
Joint sprain	22/228 (9.6%)	30
Metabolism and nutrition disorders
Decreased appetite	30/228 (13.2%)	36
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	13/228 (5.7%)	17
Nervous system disorders
Headache	67/228 (29.4%)	173
Somnolence	34/228 (14.9%)	37
Respiratory, thoracic and mediastinal disorders
Cough	22/228 (9.6%)	27
Epistaxis	22/228 (9.6%)	55
Oropharyngeal pain	12/228 (5.3%)	14
Rhinitis allergic	22/228 (9.6%)	30
Upper respiratory tract inflammation	49/228 (21.5%)	139
Skin and subcutaneous tissue disorders
Eczema	21/228 (9.2%)	29
Urticaria	12/228 (5.3%)	24
Surgical and medical procedures
Tooth extraction	14/228 (6.1%)	22

Limitations/Caveats

[Not Specified]

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.