A Safety Study of VIMOVO in Adolescents With Juvenile Idiopathic Arthritis (JIA)

• Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01544114
• Collaborator: (none)
• Enrollment: 46
• Locations: 17
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A 6-month study of the safety of VIMOVO in adolescents aged 12 to 16 years with JIA.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis (JIA)	Drug: VIMOVO 250/20; Drug: VIMOVO 375/20; Drug: VIMOVO 500/20	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 6-month, Multicenter, Open-label, Safety Study of VIMOVO (250 mg/20 mg, 375 mg/20 mg, and 500 mg/20 mg Naproxen/Esomeprazole) in Adolescents Aged 12 to 16 Years, Inclusive, With Juvenile Idiopathic Arthritis (JIA)
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: VIMOVO Three VIMOVO strengths will be used in this study: 250 mg naproxen/20 mg esomeprazole magnesium (VIMOVO 250/20), 375 mg naproxen/20 mg esomeprazole magnesium (VIMOVO 375/20), and 500 mg naproxen/20 mg esomeprazole magnesium (VIMOVO 500/20). The VIMOVO strength allocated to each participant will be determined by the participant's weight at baseline and based on investigator's discretion. The target dose of the naproxen component will be within the range of 10-20 mg/kg/day divided twice daily (BID) with a maximum daily dose of 1000 mg.

Drug: VIMOVO 250/20; 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months; Other Names: naproxen/esomeprazole ; Drug: VIMOVO 375/20; 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months; Other Names: naproxen/esomeprazole ; Drug: VIMOVO 500/20; 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months; Other Names: naproxen/esomeprazole

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug [SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.]

   An AE is defined as the development of an undesirable medical condition or the deterioration of a preexisting medical condition, whether or not considered causally related to treatment. An SAE is defined as an AE occurring during any study phase (ie, run-in, treatment, washout, follow-up), that fulfils one or more of the following criteria: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. AEs were considered treatment-emergent if they occurred after the first dose of study drug. Events were categorized as mild, moderate, and severe; participants were represented only with the maximum reported intensity.

Secondary Outcome Measures

1. Pharmacokinetics (PK) of Esomeprazole: Area Under the Concentration-Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-t]) [pre-dose, and up to 3 hours post-dose]

2. PK of Esomeprazole: Oral Plasma Clearance (CL/F) [pre-dose, and up to 3 hours post-dose]

3. PK of Esomeprazole: Absorption Rate Constant (Ka) [pre-dose, and up to 3 hours post-dose]

4. PK of Esomeprazole: Oral Volume of Distribution (V/F) [pre-dose, and up to 3 hours post-dose]

5. PK of Naproxen: Trough Plasma Concentrations [Month 1 and Month 3: pre-dose, and up to 3 hours post-dose]

   Trough concentration was defined as lowest plasma concentration from pre-dose to 3 hours post-dose, for each individual participant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Parent or legal guardian is able to provide written informed consent and patient is able to provide written assent if appropriate.

• Male and female adolescents aged 12 to 16 years at the time of enrollment.

• Diagnosed with JIA, including all the International League of Associations for Rheumatology JIA subtypes: oligoarthritis, polyarthritis (both rheumatoid factor [RF]+ and RF-), psoriatic arthritis, enthesitis-related arthritis, undifferentiated arthritis, and systemic arthritis.

• Based upon investigator judgment, it is determined appropriate for the patient to undergo 6 months of continuous treatment with VIMOVO.

• Body weight > 31 kg (68.2 lbs) and within the 5th to 95th percentile of body mass index for age.

Exclusion Criteria:

• In systemic JIA patients, presence of systemic features (ie, fever, rheumatoid rash, serositis, lymphadenopathy, macrophage activation syndrome) within 6 months prior to start of study drug.

• Currently taking (ie, within 4 weeks prior to start of drug) naproxen > 20 mg/kg/day or > 1000 mg total daily dose.

• Hemoglobin ≤ 8.5 g/dL.

• Individuals who have cardiovascular or cerebrovascular disease, based on history or risk factors.

• Any significant hepatic, renal, pulmonary, ophthalmologic, neurologic, or any other medical conditions indicated by medical/surgical history, physical, or laboratory examination that might put the patient at greater risk during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Little Rock	Arkansas	United States	72202
2	Research Site	San Francisco	California	United States	94143
3	Research Site	Aurora	Colorado	United States	80045
4	Research Site	Washington, D.C.	District of Columbia	United States	20010
5	Research Site	West Palm Beach	Florida	United States	33407
6	Research Site	Augusta	Georgia	United States	30912
7	Research Site	Chicago	Illinois	United States	60637
8	Research Site	Omaha	Nebraska	United States	68114
9	Research Site	Brooklyn	New York	United States	11203
10	Research Site	New Hyde Park	New York	United States	11040
11	Research Site	New York	New York	United States	10021
12	Research Site	Cincinnati	Ohio	United States	45229
13	Research Site	Cleveland	Ohio	United States	44195
14	Research Site	Toledo	Ohio	United States	43623
15	Research Site	Philadelphia	Pennsylvania	United States	19134
16	Research Site	Memphis	Tennessee	United States	38119
17	Research Site	Fairfax	Virginia	United States	22030

Sponsors and Collaborators

• Horizon Pharma Ireland, Ltd., Dublin Ireland

Investigators

• Study Director: Julie Ball, MS, Horizon Pharma Ireland, Ltd., Dublin Ireland

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
• ClinicalTrials.gov Identifier: NCT01544114
• Other Study ID Numbers: D1120C00037
• First Posted: Mar 5, 2012
• Last Update Posted: Oct 4, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Naproxen; Esomeprazole

Study Results

Participant Flow

Pre-assignment Detail	A total of 51 participants signed informed consent; 5 participants were not assigned to treatment (eligibility criteria not fulfilled).

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Period Title: Overall Study
STARTED	4	20	22
COMPLETED	3	16	17
NOT COMPLETED	1	4	5

Baseline Characteristics

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg	Total
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	Total of all reporting groups
Overall Participants	4	20	22	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.8 (0.96)	13.6 (1.47)	13.8 (1.33)	13.6 (1.37)
Age, Customized (Count of Participants)
12 years old	2 50%	7 35%	4 18.2%	13 28.3%
13 years old	1 25%	4 20%	7 31.8%	12 26.1%
14 years old	1 25%	2 10%	2 9.1%	5 10.9%
15 years old	0 0%	5 25%	7 31.8%	12 26.1%
16 years old	0 0%	2 10%	2 9.1%	4 8.7%
Sex: Female, Male (Count of Participants)
Female	3 75%	15 75%	15 68.2%	33 71.7%
Male	1 25%	5 25%	7 31.8%	13 28.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug
Description	An AE is defined as the development of an undesirable medical condition or the deterioration of a preexisting medical condition, whether or not considered causally related to treatment. An SAE is defined as an AE occurring during any study phase (ie, run-in, treatment, washout, follow-up), that fulfils one or more of the following criteria: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. AEs were considered treatment-emergent if they occurred after the first dose of study drug. Events were categorized as mild, moderate, and severe; participants were represented only with the maximum reported intensity.
Time Frame	SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.

Outcome Measure Data

Analysis Population Description

Safety analysis set: all participants who received at least 1 dose of study drug; participants were categorized according to the treatment medication they actually took.

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg	Total
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Measure Participants	4	20	22	46
Any TEAE	4 100%	16 80%	17 77.3%	37 80.4%
Mild TEAE	1 25%	9 45%	8 36.4%	18 39.1%
Moderate TEAE	3 75%	6 30%	9 40.9%	18 39.1%
Severe TEAE	0 0%	1 5%	0 0%	1 2.2%
Any related TEAE	1 25%	6 30%	4 18.2%	11 23.9%
Any SAE	0 0%	1 5%	0 0%	1 2.2%
Any related SAE	0 0%	1 5%	0 0%	1 2.2%
Any TEAE leading to death	0 0%	0 0%	0 0%	0 0%
Any TEAE leading to DC of study drug	1 25%	1 5%	2 9.1%	4 8.7%
Any related TEAE leading to DC of study drug	1 25%	1 5%	1 4.5%	3 6.5%

2. Secondary Outcome

Title	Pharmacokinetics (PK) of Esomeprazole: Area Under the Concentration-Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-t])
Time Frame	pre-dose, and up to 3 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Analysis Set: all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK blood sample result and no protocol deviations that would have an impact on any PK assessment; participants were categorized according to the treatment medication they actually took.

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg	Total
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Measure Participants	4	16	20	40
Geometric Mean (Geometric Coefficient of Variation) [hr*µmol/L]	2.2 (92)	1.3 (170)	1.2 (150)	1.3 (150)

3. Secondary Outcome

Title	PK of Esomeprazole: Oral Plasma Clearance (CL/F)
Time Frame	pre-dose, and up to 3 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Analysis Set: all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK blood sample result and no protocol deviations that would have an impact on any PK assessment; participants were categorized according to the treatment medication they actually took.

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg	Total
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Measure Participants	4	16	20	40
Geometric Mean (Geometric Coefficient of Variation) [L/h]	27 (92)	44 (170)	47 (150)	43 (150)

4. Secondary Outcome

Title	PK of Esomeprazole: Absorption Rate Constant (Ka)
Time Frame	pre-dose, and up to 3 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Analysis Set: all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK blood sample result and no protocol deviations that would have an impact on any PK assessment; participants were categorized according to the treatment medication they actually took.

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg	Total
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Measure Participants	4	16	20	40
Geometric Mean (Geometric Coefficient of Variation) [h^-1]	2.8 (140)	2.6 (83)	4.1 (70)	3.3 (84)

5. Secondary Outcome

Title	PK of Esomeprazole: Oral Volume of Distribution (V/F)
Time Frame	pre-dose, and up to 3 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Analysis Set: all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK blood sample result and no protocol deviations that would have an impact on any PK assessment; participants were categorized according to the treatment medication they actually took.

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg	Total
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Measure Participants	4	16	20	40
Geometric Mean (Geometric Coefficient of Variation) [L]	28 (240)	61 (120)	57 (130)	55 (130)

6. Secondary Outcome

Title	PK of Naproxen: Trough Plasma Concentrations
Description	Trough concentration was defined as lowest plasma concentration from pre-dose to 3 hours post-dose, for each individual participant.
Time Frame	Month 1 and Month 3: pre-dose, and up to 3 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Analysis Set: all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK blood sample result and no protocol deviations that would have an impact on any PK assessment; participants were categorized according to the treatment medication they actually took.

Arm/Group Title	VIMOVO 250 mg/20 mg	VIMOVO 375 mg/20 mg	VIMOVO 500 mg/20 mg
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months	500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
Measure Participants	4	17	20
Month 1	63.09 (40.1)	19.29 (1334.9)	40.71 (277.3)
Month 3	63.16 (67.3)	33.91 (476.0)	40.69 (325.4)

Adverse Events

Time Frame	SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days.
Arm/Group Title	VIMOVO 250 mg/20 mg		VIMOVO 375 mg/20 mg		VIMOVO 500 mg/20 mg		Total
Arm/Group Description	250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months		375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months		500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months		250 mg naproxen/20 mg esomeprazole magnesium, 375 mg naproxen/20 mg esomeprazole magnesium, or 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months
All Cause Mortality
	VIMOVO 250 mg/20 mg		VIMOVO 375 mg/20 mg		VIMOVO 500 mg/20 mg		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	VIMOVO 250 mg/20 mg		VIMOVO 375 mg/20 mg		VIMOVO 500 mg/20 mg		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Hepatobiliary disorders
Hepatitis Acute	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	VIMOVO 250 mg/20 mg		VIMOVO 375 mg/20 mg		VIMOVO 500 mg/20 mg		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		16/20 (80%)		17/22 (77.3%)		37/46 (80.4%)
Blood and lymphatic system disorders
Eosinophilia	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Increased Tendency to Bruise	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Ear and labyrinth disorders
Deafness	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Ear Pain	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Tinnitus	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Endocrine disorders
Hyperthyroidism	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Eye disorders
Dry Eye	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Uveitis	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Gastrointestinal disorders
Abdominal Pain Upper	0/4 (0%)		3/20 (15%)		2/22 (9.1%)		5/46 (10.9%)
Diarrhoea	0/4 (0%)		2/20 (10%)		2/22 (9.1%)		4/46 (8.7%)
Nausea	0/4 (0%)		3/20 (15%)		1/22 (4.5%)		4/46 (8.7%)
Abdominal Discomfort	0/4 (0%)		2/20 (10%)		0/22 (0%)		2/46 (4.3%)
Dyspepsia	0/4 (0%)		0/20 (0%)		2/22 (9.1%)		2/46 (4.3%)
Vomiting	0/4 (0%)		1/20 (5%)		1/22 (4.5%)		2/46 (4.3%)
Abdominal Distension	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Abdominal Pain	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Abdominal Pain Lower	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Flatulence	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Gastritis	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Mouth Ulceration	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Toothache	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
General disorders
Fatigue	0/4 (0%)		0/20 (0%)		2/22 (9.1%)		2/46 (4.3%)
Thirst	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Immune system disorders
Hypersensitivity	0/4 (0%)		1/20 (5%)		1/22 (4.5%)		2/46 (4.3%)
Infections and infestations
Upper Respiratory Tract Infection	1/4 (25%)		2/20 (10%)		6/22 (27.3%)		9/46 (19.6%)
Sinusitis	0/4 (0%)		1/20 (5%)		4/22 (18.2%)		5/46 (10.9%)
Gastroenteritis Viral	0/4 (0%)		0/20 (0%)		2/22 (9.1%)		2/46 (4.3%)
Tooth Infection	0/4 (0%)		1/20 (5%)		1/22 (4.5%)		2/46 (4.3%)
Bacterial Vaginosis	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Fungal Infection	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Helicobacter Infection	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Influenza	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Localized Infection	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Nasopharyngitis	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Otitis Media	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Trichomoniasis	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Urinary Tract Infection	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Injury, poisoning and procedural complications
Ligament Sprain	0/4 (0%)		0/20 (0%)		3/22 (13.6%)		3/46 (6.5%)
Contusion	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Eye Injury	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Limb Injury	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Investigations
Liver Function Test Abnormal	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Weight Decreased	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Metabolism and nutrition disorders
Decreased Appetite	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Dehydration	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Ketoacidosis	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Musculoskeletal and connective tissue disorders
Back Pain	1/4 (25%)		1/20 (5%)		0/22 (0%)		2/46 (4.3%)
Pain in Extremity	0/4 (0%)		1/20 (5%)		1/22 (4.5%)		2/46 (4.3%)
Arthralgia	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Juvenile Idiopathic Arthritis	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Tendon Pain	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma	1/4 (25%)		1/20 (5%)		0/22 (0%)		2/46 (4.3%)
Nervous system disorders
Headache	1/4 (25%)		1/20 (5%)		2/22 (9.1%)		4/46 (8.7%)
Arachnoid Cyst	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Dizziness	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Hypoaesthesia	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Renal and urinary disorders
Pollakiuria	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Reproductive system and breast disorders
Breast Mass	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Menstruation Irregular	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Ovarian Cyst	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Cough	0/4 (0%)		1/20 (5%)		1/22 (4.5%)		2/46 (4.3%)
Skin and subcutaneous tissue disorders
Acne	0/4 (0%)		0/20 (0%)		1/22 (4.5%)		1/46 (2.2%)
Dermatitis Contact	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)
Ingrowing Nail	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Rash	0/4 (0%)		1/20 (5%)		0/22 (0%)		1/46 (2.2%)
Urticaria	1/4 (25%)		0/20 (0%)		0/22 (0%)		1/46 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .