Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy

• Sponsor: Sarepta Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02420379
• Collaborator: (none)
• Enrollment: 33
• Locations: 13
• Arms: 2
• Actual Duration (Months): 41.6
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label study to assess the safety, tolerability, efficacy and pharmacokinetics of eteplirsen in patients with early stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy (DMD)	Drug: eteplirsen	Phase 2

Detailed Description

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.

Clinical efficacy, including functional tests and MRI, will be assessed at regularly scheduled study visits. Patients will undergo one baseline and one follow-up muscle biopsy.

Population and serial PK will be collected.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multi-Center Study to Evaluate the Safety, Efficacy and Tolerability of Eteplirsen in Early Stage Duchenne Muscular Dystrophy
• Actual Study Start Date: Jun 30, 2015
• Actual Primary Completion Date: Dec 17, 2018
• Actual Study Completion Date: Dec 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open-Label Approximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg .	Drug: eteplirsen; Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.; Other Names: AVI-4658 EXONDYS 51®
No Intervention: Control Group Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation [Baseline up to 100 weeks]

   Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment emergent adverse events were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug [up to 100 weeks]) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

2. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs [Baseline up to 100 weeks]

   Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.

3. Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs [Baseline up to 100 weeks]

   Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.

4. Number of Participants With at Least One Abnormal Physical Examination Finding [Baseline up to 100 weeks]

   Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.

5. Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs [Baseline up to 96 weeks]

   Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.

6. Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs [Baseline up to 96 weeks]

   Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.

Secondary Outcome Measures

1. Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96 [Baseline, Week 48 and 96]

   Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 48 and 96 was reported. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.

2. Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96 [Baseline, Week 48 and 96]

   Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry at Week 48 and 96 was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 6 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male 4-6 years of age.

• Diagnosis of DMD, genotypically confirmed.

• Stable dose of oral corticosteroids for at least 12 weeks or has not received corticosteroids for at least 12 weeks.

• Intact right and left biceps muscles or two alternative upper arm muscle groups.

• Parent that is willing to provide consent and comply with study procedures.

Exclusion Criteria:

• Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids).

• Previous or current treatment with any other experimental treatments within 12 weeks or participation in any other clinical trial within 6 months.

• Major surgery within 3 months prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study activities.

• Presence of other clinically significant illness.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neuromuscular Research Center of Arizona	Phoenix	Arizona	United States	85028
2	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
3	University of California, Davis Medical Center	Sacramento	California	United States	95817
4	Stanford University Medical Center	Stanford	California	United States	94305
5	University of Florida, Shands Hospital	Gainesville	Florida	United States	32610
6	Rare Disease Research Center	Atlanta	Georgia	United States	30318
7	Children's Hospital of Atlanta	Atlanta	Georgia	United States	30324
8	University of Iowa Children's Hospital	Iowa City	Iowa	United States	52242
9	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
10	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
11	Shriners Hospital for Children	Portland	Oregon	United States	97239
12	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
13	Seattle Children's Hospital	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Sarepta Therapeutics, Inc.

Investigators

• Study Director: Medical Director, Sarepta Therapeutics, Inc.

Study Documents (Full-Text)

• Statistical Analysis Plan - Feb 11, 2019
• Study Protocol - Jun 8, 2017

More Information

Publications

None provided.

• Responsible Party: Sarepta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02420379
• Other Study ID Numbers: 4658-203
• First Posted: Apr 17, 2015
• Last Update Posted: Jan 25, 2021
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sarepta Therapeutics, Inc.: DMD; Duchenne muscular dystrophy; eteplirsen; Dystrophin; exon 51
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

Participant Flow

Recruitment Details	The study was conducted at 13 sites in the United States.
Pre-assignment Detail	A total of 33 participants were enrolled in the study treatment.

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
Period Title: Overall Study
STARTED	26	7
COMPLETED	25	3
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)	Total
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.	Total of all reporting groups
Overall Participants	26	7	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.0 (0.82)	5.0 (1.00)	5.0 (0.85)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	26 100%	7 100%	33 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 19.2%	0 0%	5 15.2%
Not Hispanic or Latino	21 80.8%	7 100%	28 84.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 7.7%	1 14.3%	3 9.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 3.8%	0 0%	1 3%
White	22 84.6%	6 85.7%	28 84.8%
More than one race	1 3.8%	0 0%	1 3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%	7 100%	33 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Description	Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment emergent adverse events were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug [up to 100 weeks]) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Time Frame	Baseline up to 100 weeks

Outcome Measure Data

Analysis Population Description

Full set included all participants who were enrolled in the eteplirsen group and received at least 1 dose of eteplirsen as well as all participants who were enrolled in the untreated group and had at least 1 assessment post-enrollment assessment.

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
Measure Participants	26	7
Participants with TEAEs	26 100%	5 71.4%
Participants with Serious TEAEs	4 15.4%	0 0%
Participants with TEAEs leading to discontinuation	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs
Description	Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Time Frame	Baseline up to 100 weeks

Outcome Measure Data

Analysis Population Description

Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
Measure Participants	26	7
SC: Blood creatine phosphokinase increased	1 3.8%	0 0%
Hematology: Anaemia	1 3.8%	0 0%
Hematology: Iron deficiency Anaemia	1 3.8%	0 0%
Urinalysis: chromaturia	3 11.5%	0 0%
Urinalysis: pollakiuria	1 3.8%	0 0%
Coagulation: Thrombocytopenia	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
Description	Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Time Frame	Baseline up to 100 weeks

Outcome Measure Data

Analysis Population Description

Full set included all participants who were enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
Measure Participants	26	7
Pyrexia	11 42.3%	1 14.3%
Pulse pressure increased	1 3.8%	0 0%
Tachycardia	1 3.8%	0 0%

4. Primary Outcome

Title	Number of Participants With at Least One Abnormal Physical Examination Finding
Description	Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.
Time Frame	Baseline up to 100 weeks

Outcome Measure Data

Analysis Population Description

Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment postenrollment assessment.

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
Measure Participants	26	7
Count of Participants [Participants]	23 88.5%	4 57.1%

5. Primary Outcome

Title	Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs
Description	Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.
Time Frame	Baseline up to 96 weeks

Outcome Measure Data

Analysis Population Description

Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at 1 assessment post-enrollment assessment.

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
Measure Participants	26	7
Count of Participants [Participants]	1 3.8%	0 0%

6. Primary Outcome

Title	Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs
Description	Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.
Time Frame	Baseline up to 96 weeks

Outcome Measure Data

Analysis Population Description

Full set included all participants who are enrolled in the eteplirsen group and receive at least 1 dose of eteplirsen as well as all participants who are enrolled in the untreated group who have at least 1 assessment post-enrollment assessment.

Arm/Group Title	Eteplirsen 30 mg/kg	Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.	Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
Measure Participants	26	7
Count of Participants [Participants]	1 3.8%	0 0%

7. Secondary Outcome

Title	Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96
Description	Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 48 and 96 was reported. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.
Time Frame	Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description

Muscle Biopsy Set included all participants who received at least 1 dose of eteplirsen and who had data from both baseline (pre-treatment) and Week 48 or 96 (on-treatment) muscle biopsy samples. Data for this outcome was not planned to be collected and analyzed for control group (untreated) (non-exon 51 amenable participants). Here, number of participants analyzed signifies participants who were evaluable at specific time point.

Arm/Group Title	Eteplirsen 30 mg/kg
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.
Measure Participants	25
Change at Week 48	0.102 (0.0896)
Change at Week 96	0.321 (0.4863)

8. Secondary Outcome

Title	Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96
Description	Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry at Week 48 and 96 was reported.
Time Frame	Baseline, Week 48 and 96

Outcome Measure Data

Analysis Population Description

Muscle Biopsy Set included all participants who received at least 1 dose of eteplirsen and who had data from both baseline (pre-treatment) and Week 48 or 96 (on-treatment) muscle biopsy samples. Data for this outcome was not planned to be collected and analyzed for control group (untreated) (non-exon 51 amenable participants). Here, number of participants analyzed signifies participants who were evaluable at specific time point.

Arm/Group Title	Eteplirsen 30 mg/kg
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.
Measure Participants	25
Change at Week 48	0.004 (0.0096)
Change at Week 96	0.015 (0.0175)

Adverse Events

Time Frame	Baseline up to 100 weeks
Arm/Group Title	Eteplirsen 30 mg/kg		Control Group (Untreated) (Non-exon 51 Amenable Participants)
Arm/Group Description	Participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusions, once weekly, for 96 weeks.		Participants with DMD not amenable to exon 51 skipping were observed for 96 weeks.
All Cause Mortality
	Eteplirsen 30 mg/kg		Control Group (Untreated) (Non-exon 51 Amenable Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/7 (0%)
Serious Adverse Events
	Eteplirsen 30 mg/kg		Control Group (Untreated) (Non-exon 51 Amenable Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/26 (15.4%)		0/7 (0%)
Infections and infestations
Coxsackie viral infection	1/26 (3.8%)		0/7 (0%)
Influenza	1/26 (3.8%)		0/7 (0%)
Rhinovirus infection	1/26 (3.8%)		0/7 (0%)
Injury, poisoning and procedural complications
Foreign body	1/26 (3.8%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/26 (3.8%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Eteplirsen 30 mg/kg		Control Group (Untreated) (Non-exon 51 Amenable Participants)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		5/7 (71.4%)
Ear and labyrinth disorders
Ear pain	7/26 (26.9%)		0/7 (0%)
Gastrointestinal disorders
Vomiting	11/26 (42.3%)		2/7 (28.6%)
Diarrhoea	7/26 (26.9%)		1/7 (14.3%)
Abdominal pain	5/26 (19.2%)		0/7 (0%)
Abdominal pain upper	5/26 (19.2%)		0/7 (0%)
Constipation	3/26 (11.5%)		1/7 (14.3%)
Nausea	2/26 (7.7%)		1/7 (14.3%)
Dental caries	2/26 (7.7%)		0/7 (0%)
General disorders
Pyrexia	11/26 (42.3%)		1/7 (14.3%)
Catheter site pain	3/26 (11.5%)		0/7 (0%)
Catheter site bruise	2/26 (7.7%)		0/7 (0%)
Immune system disorders
Hypersensitivity	0/26 (0%)		1/7 (14.3%)
Infections and infestations
Nasopharyngitis	16/26 (61.5%)		2/7 (28.6%)
Upper respiratory tract infection	11/26 (42.3%)		1/7 (14.3%)
Ear infection	8/26 (30.8%)		1/7 (14.3%)
Influenza	5/26 (19.2%)		0/7 (0%)
Otitis media	2/26 (7.7%)		1/7 (14.3%)
Pharyngitis streptococcal	3/26 (11.5%)		0/7 (0%)
Rhinitis	3/26 (11.5%)		0/7 (0%)
Conjunctivitis	2/26 (7.7%)		0/7 (0%)
Gastroenteritis viral	2/26 (7.7%)		0/7 (0%)
Staphylococcal infection	2/26 (7.7%)		0/7 (0%)
Impetigo	0/26 (0%)		1/7 (14.3%)
Injury, poisoning and procedural complications
Fall	9/26 (34.6%)		0/7 (0%)
Contusion	5/26 (19.2%)		0/7 (0%)
Procedural pain	4/26 (15.4%)		0/7 (0%)
Skin abrasion	4/26 (15.4%)		0/7 (0%)
Scratch	3/26 (11.5%)		0/7 (0%)
Head injury	2/26 (7.7%)		0/7 (0%)
Sunburn	2/26 (7.7%)		0/7 (0%)
Ligament sprain	0/26 (0%)		1/7 (14.3%)
Investigations
Cardiac murmur	4/26 (15.4%)		0/7 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/26 (7.7%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	8/26 (30.8%)		0/7 (0%)
Arthralgia	6/26 (23.1%)		0/7 (0%)
Back pain	4/26 (15.4%)		0/7 (0%)
Muscle spasms	4/26 (15.4%)		0/7 (0%)
Muscular weakness	4/26 (15.4%)		0/7 (0%)
Musculoskeletal pain	2/26 (7.7%)		0/7 (0%)
Scoliosis	0/26 (0%)		1/7 (14.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	2/26 (7.7%)		0/7 (0%)
Nervous system disorders
Headache	10/26 (38.5%)		0/7 (0%)
Migraine	2/26 (7.7%)		0/7 (0%)
Psychiatric disorders
Aggression	2/26 (7.7%)		0/7 (0%)
Renal and urinary disorders
Chromaturia	3/26 (11.5%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	23/26 (88.5%)		3/7 (42.9%)
Rhinorrhoea	13/26 (50%)		0/7 (0%)
Nasal congestion	10/26 (38.5%)		0/7 (0%)
Epistaxis	5/26 (19.2%)		0/7 (0%)
Oropharyngeal pain	4/26 (15.4%)		0/7 (0%)
Productive cough	2/26 (7.7%)		0/7 (0%)
Upper respiratory tract congestion	2/26 (7.7%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Rash	13/26 (50%)		0/7 (0%)
Dermatitis contact	3/26 (11.5%)		0/7 (0%)
Keloid scar	2/26 (7.7%)		0/7 (0%)
Rash pruritic	2/26 (7.7%)		0/7 (0%)
Surgical and medical procedures
Adenoidectomy	0/26 (0%)		1/7 (14.3%)
Myringotomy	0/26 (0%)		1/7 (14.3%)
Orchidopexy	0/26 (0%)		1/7 (14.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The most restrictive relevant agreement provides that the PI can only publish the study results with the approval of Sponsor.