Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00570128
• Collaborator: Pfizer (Industry)
• Enrollment: 129
• Locations: 31
• Arms: 2
• Actual Duration (Months): 9.7
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether donepezil HCl is effective and safe in improving cognitive dysfunction exhibited by children and adolescents with Down syndrome (DS). Effectiveness will be measured by rating communication, daily living skills, and social skills and relationships in subjects aged 10 to 17.

Condition or Disease	Intervention/Treatment	Phase
Down Syndrome	Drug: Donepezil HCl; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 10-Week, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Donepezil Hydrochloride (Aricept®) in the Treatment of the Cognitive Dysfunction Exhibited by Children With Down Syndrome
• Actual Study Start Date: Nov 16, 2007
• Actual Primary Completion Date: Sep 5, 2008
• Actual Study Completion Date: Sep 5, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Donepezil HCl	Drug: Donepezil HCl; Blinded donepezil 2.5 milligram per day (mg/day) (2.5 milliliter per day [mL/day]) orally for participants with body weight (BW) 20 and less than (<) 25 kilogram (kg), 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW greater than or equal to (>=) 50 kg liquid formulation (1 milligram per 1 milliliter [1 mg/1 mL]) (titrated to 0.1 to 0.2 milligram per kilogram per day [mg/kg/day] based on BW).; Other Names: Aricept
Placebo Comparator: Placebo	Drug: Placebo; Liquid formulation matched to active treatment for oral administration.

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-Domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 10-Last Observation Carried Forward (LOCF) [Baseline, Week 10]

   The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, and writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a standard deviation (SD) of 15.

Secondary Outcome Measures

1. Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 4 and 10-Observed Cases (OC) [Baseline, Week 4 and Week 10]

   The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a SD of 15.

2. Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC [Baseline, Week 4 and Week 10]

   The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with down syndrome (DS) across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.

3. Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF [Baseline, Week 10]

   The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with DS across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ages 10 to 17 years old, weight more than or equal to 20 kg

• Male and female

• Vineland-II Adaptive Behavior Scales (VABS-II)/Parent/Caregiver Rating Form (PCRF) standard composite score greater than (>) 55

• Diagnosis of DS (trisomy 21) documented by chromosomal analysis (karyotyping). If such documentation is not available at screening, karyotyping will be performed with the screening labs and must be documented prior to baseline visit.

• Naïve to approved or unapproved cholinesterase inhibitors is preferred however, prior use of these medications is allowed, provided that the medication was discontinued at least 3 months prior to screening and that it was not discontinued for lack of tolerability or efficacy or for the sole purpose of enrolling the subject in the study.

• Subjects residing in the community

• Must be expected to complete all procedures scheduled during the Screening and Baseline visits including all efficacy and safety parameters.

• Must speak English and be verbal and able to be understood most of the time and must not use other forms of communication, signs, symbol boards or devices to supplement his/her communication ability

• Must have a parent or other reliable caregiver who agrees to accompany the subject to all clinic visits, provide information about the subject as required by the protocol, and ensure compliance with the medication schedule

• a Parent or Caregiver must be a constant and reliable informant with sufficient contact with the subject to have detailed knowledge of the subject's adaptive behavior in order to be able to complete the VABS-II/PCRF accurately. The same individual should complete the form at every visit.

• Should be in good general health with no medical conditions that are considered both clinically significant and unstable

• Clinical laboratory values within normal limits or abnormalities considered not clinically significant by the investigator and sponsor

• Stable Type I (insulin-dependent) or Type II diabetes are eligible provided they are monitored regularly prior to and during the study to ensure adequate glucose control (fasting blood glucose <140 milligram per deciliter (mg/dl) and glycosylated hemoglobin [hemoglobin A1c] <8 percent (%) at screening).

• Thyroid disease also may be included in the study provided they are euthyroid and stable on treatment for at least 3 months prior to screening.

• History of seizure disorder is allowed provided that subjects are on stable treatment for at least 3 months and have not had a seizure within the past 6 months.

• Independent in ambulation or ambulatory aided (example, walker or cane, wheelchair), vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for achieving VABS-II/PCRF composite standard scores >55 and for cooperating with examinations and the Test of Verbal Expression and Reasoning (TOVER).

Exclusion Criteria:

• Ages <10 or >17 years

• Active or clinically significant conditions affecting absorption, distribution or metabolism of the study medication (example, inflammatory bowel disease, gastric or duodenal ulcers or severe lactose intolerance)

• Known hypersensitivity to piperidine derivatives or cholinesterase inhibitors

• Currently receiving cholinesterase inhibitors or who have received them in the 3 months prior to screening or with prior use >3 months prior to screening who stopped for lack of efficacy or tolerability

• No reliable parent or caregiver, or participants, or caregivers who are unwilling or unable to complete any of the outcome measures and fulfill the requirements of this study

• Clinically significant obstructive pulmonary disease or asthma untreated or not controlled by treatment within 3 months prior to screening

• Recent (less than or equal to 2 years) hematologic/oncologic disorders (mild anemia allowed)

• Evidence of active, clinically significant, and unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease

• Current Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) diagnosis of Major Depressive Disorder (MDD) or any current primary psychiatric diagnosis other than DS (as per DSM-IV)

• Any condition which would make the subject or the caregiver, in the opinion of the investigator, unsuitable for the study

• Unsuitability which includes female subjects who have begun menstruation and are thus of child-bearing potential, who may be sexually active and who are not practicing an effective means of birth control.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Clinical Study Centers, L.L.C.	Little Rock	Arkansas	United States	72205
3	Neufeld Medical Group, Inc.	Los Angeles	California	United States	90048
4	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609
5	University of California, Irvine Medical Center, Department of Pediatrics	Orange	California	United States	92868
6	UCSD Pediatric Pharmacology Research Unit	San Diego	California	United States	92123
7	Rocky Mountain Pediatrics	Lakewood	Colorado	United States	80214
8	Neuropsychiatric Research Center of South West Florida	Fort Myers	Florida	United States	33912
9	Miami Children's Hospital, Clinical Research Center	Miami	Florida	United States	33155-3009
10	Community Research Foundation	Miami	Florida	United States	33155
11	Miami Children's Hospital, Brain Institute	Miami	Florida	United States	33155
12	Meridien Research	Saint Petersburg	Florida	United States	33709
13	Lazlo J. Mate, MD	West Palm Beach	Florida	United States	33407
14	Child Neurology Associates, PC	Atlanta	Georgia	United States	30342
15	Medical Genetics and Neuro Development Center	Zionsville	Indiana	United States	46077
16	Hurley Medical Center	Flint	Michigan	United States	48503
17	Saint Mayr's Health Care	Grand Rapids	Michigan	United States	49503
18	Regions Hospital	Saint Paul	Minnesota	United States	55101-2529
19	Washington University School of Medicine, Division of Genetics and Genomic Medicine	Saint Louis	Missouri	United States	63110
20	Midwest Children's Health Research Institute, LLC	Lincoln	Nebraska	United States	68504
21	Clinical Research Center of New Jersey	Voorhees	New Jersey	United States	08043
22	Duke University Medical Center	Durham	North Carolina	United States	27710
23	Metrohealth Medical Center, Division of Psychiatry	Cleveland	Ohio	United States	44109
24	Valko and Associates	Toledo	Ohio	United States	43606
25	Tulsa Clinical Research LLC	Tulsa	Oklahoma	United States	74104-5428
26	Medical University of South Carolina, Division of Genetics and Developmental and Behavioral Pediatrics	Charleston	South Carolina	United States	29425
27	Vanderbilt Children's Hospital	Nashville	Tennessee	United States	37232-9225
28	Down Syndrome Clinic of Houston	Houston	Texas	United States	77030
29	Alamo City Clinical Research, LLC	San Antonio	Texas	United States	78258
30	Road Runner Research	San Antonio	Texas	United States	78258
31	Northwest Clinical Research Center	Bellevue	Washington	United States	98004

Sponsors and Collaborators

• Eisai Inc.
• Pfizer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT00570128
• Other Study ID Numbers: E2020-A001-219; A2501059
• First Posted: Dec 10, 2007
• Last Update Posted: Apr 19, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Eisai Inc.: Down Syndrome; trisomy 21
• Additional relevant MeSH terms: Down Syndrome; Syndrome; Cognitive Dysfunction; Donepezil

Study Results

Participant Flow

Recruitment Details	This study was conducted at 35 centers in the United States during the period of 16 November 2007 to 05 September 2008.

Arm/Group Title	Donepezil HCl	Placebo
Arm/Group Description	Blinded donepezil hydrochloride (HCl) 2.5 milligram per day (mg/day) (2.5 milliliter per day [mL/day]) orally for participants with body weight (BW) 20 and less than (<) 25 kilogram (kg), 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW greater than or equal to (>=) 50 kg liquid formulation (1 milligram per 1 milliliter [1 mg/1 mL]) (titrated to 0.1 to 0.2 milligram per kilogram per day [mg/kg/day] based on BW).	Liquid formulation matched to active treatment for oral administration.
Period Title: Overall Study
STARTED	64	65
Intent to Treat (ITT) Population	62	65
COMPLETED	60	65
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Donepezil HCl	Placebo	Total
Arm/Group Description	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).	Liquid formulation matched to active treatment for oral administration.	Total of all reporting groups
Overall Participants	64	65	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.0 (2.3)	13.0 (2.1)	13.0 (2.3)
Sex: Female, Male (Count of Participants)
Female	28 43.8%	35 53.8%	63 48.8%
Male	36 56.3%	30 46.2%	66 51.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.6%	4 6.2%	5 3.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 4.7%	3 4.6%	6 4.7%
White	54 84.4%	57 87.7%	111 86%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 9.4%	1 1.5%	7 5.4%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-Domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 10-Last Observation Carried Forward (LOCF)
Description	The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, and writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a standard deviation (SD) of 15.
Time Frame	Baseline, Week 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who received at least one dose of study drug and had at least one post-baseline assessment for at least one efficacy variable irrespective of compliance and protocol violations. Here "Overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Donepezil HCl	Placebo
Arm/Group Description	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).	Liquid formulation matched to active treatment for oral administration.
Measure Participants	61	65
Baseline	83.1 (15.5)	85.7 (15.8)
Mean change from baseline at Week 10	4.74 (9.2)	4.22 (8.5)

2. Secondary Outcome

Title	Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 4 and 10-Observed Cases (OC)
Description	The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a SD of 15.
Time Frame	Baseline, Week 4 and Week 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who received at least one dose of study drug and had at least one post-baseline assessment for at least one efficacy variable irrespective of compliance and protocol violations. Here "Overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure. Here "Number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Arm/Group Title	Donepezil HCl	Placebo
Arm/Group Description	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).	Liquid formulation matched to active treatment for oral administration.
Measure Participants	61	65
Baseline	83.1 (15.5)	85.7 (15.8)
Mean change from baseline at Week 4	1.5 (6.4)	2.6 (8.5)
Mean change from baseline at Week 10	5.1 (9.6)	4.2 (8.6)

3. Secondary Outcome

Title	Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC
Description	The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with down syndrome (DS) across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.
Time Frame	Baseline, Week 4 and Week 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who received at least one dose of study drug and had at least one post-baseline assessment for at least one efficacy variable irrespective of compliance and protocol violations. Here "Overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure. Here "Number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Arm/Group Title	Donepezil HCl	Placebo
Arm/Group Description	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).	Liquid formulation matched to active treatment for oral administration.
Measure Participants	62	64
Baseline	20.7 (12.2)	21.6 (11.4)
Mean change from baseline at Week 4	1.2 (6.4)	0.9 (8.5)
Mean change from baseline at Week 10	2.6 (6.2)	1.9 (5.5)

4. Secondary Outcome

Title	Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF
Description	The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with DS across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.
Time Frame	Baseline, Week 10

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants who received at least one dose of study drug and had at least one post-baseline assessment for at least one efficacy variable irrespective of compliance and protocol violations. Here "Overall number of participants analyzed, N" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Donepezil HCl	Placebo
Arm/Group Description	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).	Liquid formulation matched to active treatment for oral administration.
Measure Participants	62	64
Baseline	20.7 (12.2)	21.6 (11.4)
Mean change from baseline at Week 10	2.4 (6.0)	2.1 (5.5)

Adverse Events

Time Frame	Baseline up to 10 months
Arm/Group Title	Donepezil HCl		Placebo
Arm/Group Description	Blinded donepezil HCl 2.5 mg/day (2.5 mL/day) orally for participants with BW 20 and <25 kg, 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW >=50 kg liquid formulation (1 mg/1 mL) (titrated to 0.1 to 0.2 mg/kg/day based on BW).		Liquid formulation matched to active treatment for oral administration.
All Cause Mortality
	Donepezil HCl		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/64 (0%)		0/65 (0%)
Serious Adverse Events
	Donepezil HCl		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/64 (0%)		1/65 (1.5%)
Infections and infestations
Gastroenteritis	0/64 (0%)		1/65 (1.5%)
Metabolism and nutrition disorders
Dehydration	0/64 (0%)		1/65 (1.5%)
Other (Not Including Serious) Adverse Events
	Donepezil HCl		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/64 (70.3%)		42/65 (64.6%)
Gastrointestinal disorders
Abdominal pain, upper	2/64 (3.1%)		1/65 (1.5%)
Constipation	0/64 (0%)		2/65 (3.1%)
Diarrhea	11/64 (17.2%)		10/65 (15.4%)
Fecal incontinence	2/64 (3.1%)		0/65 (0%)
Nausea	5/64 (7.8%)		2/65 (3.1%)
Vomiting	8/64 (12.5%)		2/65 (3.1%)
General disorders
Fatigue	1/64 (1.6%)		2/65 (3.1%)
Pyrexia	2/64 (3.1%)		2/65 (3.1%)
Infections and infestations
Bronchitis	2/64 (3.1%)		0/65 (0%)
Ear infection	1/64 (1.6%)		3/65 (4.6%)
Gastroenteritis	0/64 (0%)		2/65 (3.1%)
Gastroenteritis viral	2/64 (3.1%)		1/65 (1.5%)
Nasopharyngitis	0/64 (0%)		4/65 (6.2%)
Pharyngitis	3/64 (4.7%)		1/65 (1.5%)
Sinusitis	1/64 (1.6%)		3/65 (4.6%)
Upper respiratory tract infection	6/64 (9.4%)		5/65 (7.7%)
Viral infection	2/64 (3.1%)		0/65 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/64 (1.6%)		3/65 (4.6%)
Nervous system disorders
Headache	5/64 (7.8%)		2/65 (3.1%)
Lethargy	2/64 (3.1%)		0/65 (0%)
Somnolence	2/64 (3.1%)		0/65 (0%)
Psychiatric disorders
Insomnia	0/64 (0%)		2/65 (3.1%)
Respiratory, thoracic and mediastinal disorders
Cough	4/64 (6.3%)		1/65 (1.5%)
Nasal congestion	1/64 (1.6%)		2/65 (3.1%)
Rhinitis allergic	2/64 (3.1%)		0/65 (0%)
Skin and subcutaneous tissue disorders
Rash	3/64 (4.7%)		2/65 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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