Study of Recombinant Human N-acetylgalactosamine 4-sulfatase (rhASB) in Patients With MPS VI

• Sponsor: BioMarin Pharmaceutical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00067470
• Collaborator: (none)
• Enrollment: 39
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 6.5

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the ability of rhASB versus placebo to enhance endurance in patients with Mucopolysaccharidosis VI (MPS VI), as evidenced by an increase in the number of meters walked in the 12 minute walk test at Week 24 compared with baseline.

Condition or Disease	Intervention/Treatment	Phase
Mucopolysaccharidosis VI	Drug: Placebo; Drug: N-acetylgalactosamine 4-sulfatase	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Study Start Date: Sep 1, 2003
• Study Completion Date: Mar 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo
Active Comparator: rhASB	Drug: N-acetylgalactosamine 4-sulfatase; Other Names: rhASB

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in 12-minute Walk Test at 24 Weeks [baseline and 24 weeks]

   Number of meters walked in 12 minutes at week 24 minus number of meters walked in 12 minutes at baseline

Secondary Outcome Measures

1. Change From Baseline in 3-minute Stair Climb at 24 Weeks [baseline and 24 weeks]

   Number of stairs climbed per minute in 3 minutes at 24 weeks minus number of stairs climbed per minute in 3 minutes at baseline

2. Change From Baseline in Urinary GAG (uGAG) at 24 Weeks [baseline and 24 weeks]

   Glycosaminoglycan (GAG) level measured in urine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Patient consent

• Patient must be seven years of age or older

• Patient must have documented biochemical or genetic proof of MPS VI

• The patient must be able to walk independently at least 5 meters and no more than 270 meters in the first 6 minutes, or no more then 400 meters total in 12 minutes, in the screening 12-minute walk test

• If female of childbearing potential, patient must have a negative pregnancy test

Exclusion Criteria

• Patient is under consideration for or has undergone a successful bone marrow transplant (BMT)

• Patient refuses or is unable to complete all screening evaluations

• Pregnant or lactating patient

• Patient has received an investigational drug within 30 days prior to study enrollment

• Patient has been previously treated with rhASB

• Patient has a medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly confound study results or decrease study compliance

• The patient has clinically significant spinal cord compression

• The patient has known hypersensitivity to rhASB or to components of the active or placebo test solutions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BioMarin Pharmaceutical Inc.	Novato	California	United States	94949

Sponsors and Collaborators

• BioMarin Pharmaceutical

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00067470
• Other Study ID Numbers: ASB-03-05
• First Posted: Aug 25, 2003
• Last Update Posted: Dec 24, 2009
• Last Verified: Dec 1, 2009

• Additional relevant MeSH terms: Mucopolysaccharidoses; Mucopolysaccharidosis VI

Study Results

Participant Flow

Recruitment Details	Study Locations:Oakland, CA, USA Mainz, Germany Manchester, England Porto Alegre, Brazil Lyon, France Porto, Portugal Study Duration: 24 weeks First enrollment: 21 July 2003 Last Dose Given: 1 April 2004 Last Assessment: 8 April 2004

Arm/Group Title	rhASB	Placebo
Arm/Group Description	Intravenous (IV) recombinant human arylsulfatase(rhASB) at 1.0 mg/kg	Intravenous (IV) placebo solution at a volume equivalent to that needed for a 1.0 mg/kg dose of rhASB
Period Title: Overall Study
STARTED	19	20
COMPLETED	19	19
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	rhASB	Placebo	Total
Arm/Group Description	Intravenous (IV) recombinant human arylsulfatase(rhASB) at 1.0 mg/kg	Intravenous (IV) placebo solution at a volume equivalent to that needed for a 1.0 mg/kg dose of rhASB	Total of all reporting groups
Overall Participants	19	20	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.7 (6.47)	10.7 (4.35)	12.2 (5.62)
Sex: Female, Male (Count of Participants)
Female	12 63.2%	14 70%	26 66.7%
Male	7 36.8%	6 30%	13 33.3%
Race/Ethnicity, Customized (participants) [Number]
White, non-Hispanic	15 78.9%	9 45%	24 61.5%
Hispanic	1 5.3%	3 15%	4 10.3%
Black	1 5.3%	2 10%	3 7.7%
Asian	1 5.3%	1 5%	2 5.1%
Indigenous	1 5.3%	1 5%	2 5.1%
Other	0 0%	4 20%	4 10.3%
Region of Enrollment (participants) [Number]
United States	2 10.5%	4 20%	6 15.4%
Germany	4 21.1%	4 20%	8 20.5%
United Kingdom	3 15.8%	3 15%	6 15.4%
Brazil	4 21.1%	4 20%	8 20.5%
France	2 10.5%	3 15%	5 12.8%
Portugal	4 21.1%	2 10%	6 15.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in 12-minute Walk Test at 24 Weeks
Description	Number of meters walked in 12 minutes at week 24 minus number of meters walked in 12 minutes at baseline
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

The efficacy analysis included all subjects except one from the placebo group who withdrew from the study prior to the week 24 assessment.

Arm/Group Title	rhASB	Placebo
Arm/Group Description	Intravenous (IV) recombinant human arylsulfatase(rhASB) at 1.0 mg/kg	Intravenous (IV) placebo solution at a volume equivalent to that needed for a 1.0 mg/kg dose of rhASB
Measure Participants	19	19
Mean (Standard Deviation) [meters]	109 (154)	26 (122)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhASB, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	92
	Confidence Interval	() 95%; 11 to 172
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 40
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in 3-minute Stair Climb at 24 Weeks
Description	Number of stairs climbed per minute in 3 minutes at 24 weeks minus number of stairs climbed per minute in 3 minutes at baseline
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

The efficacy analysis included all subjects except one from the placbo group who withdrew from the study prior to the week 24 assessment.

Arm/Group Title	rhASB	Placebo
Arm/Group Description	Intravenous (IV) recombinant human arylsulfatase(rhASB) at 1.0 mg/kg	Intravenous (IV) placebo solution at a volume equivalent to that needed for a 1.0 mg/kg dose of rhASB
Measure Participants	19	19
Mean (Standard Deviation) [stairs/min]	7.4 (9.9)	2.7 (6.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	rhASB, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	Regression, Linear
	Comments	The raw data were adjusted for the observed differences in baseline between the groups and fitted to a longitudinal repeated measures linear model.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.7
	Confidence Interval	() 95%; -0.1 to 11.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Urinary GAG (uGAG) at 24 Weeks
Description	Glycosaminoglycan (GAG) level measured in urine
Time Frame	baseline and 24 weeks

Outcome Measure Data

Analysis Population Description

Baseline uGAG level was measured for 19 rhASB-treated subjects and 20 placebo-treated subjects. However, uGAG levels at 24 weeks were measured for 19 rhASB-treated subjects and 19 placebo-treated subjects, because 1 placebo-treated subject withdrew from the study before week 24.

Arm/Group Title	rhASB	Placebo
Arm/Group Description	Intravenous (IV) recombinant human arylsulfatase(rhASB) at 1.0 mg/kg	Intravenous (IV) placebo solution at a volume equivalent to that needed for a 1.0 mg/kg dose of rhASB
Measure Participants	19	19
Baseline Urinary GAG Level	346 (128)	330 (114)
24-week Urinary GAG Level	85 (35)	317 (80)

Adverse Events

Arm/Group Title	rhASB		Placebo
Arm/Group Description	Intravenous (IV) recombinant human arylsulfatase(rhASB) at 1.0 mg/kg		Intravenous (IV) placebo solution at a volume equivalent to that needed for a 1.0 mg/kg dose of rhASB
All Cause Mortality
	rhASB		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	rhASB		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)		4/20 (20%)
Cardiac disorders
Obstructive airways disorder	0/19 (0%)	0	1/20 (5%)	1
Eye disorders
Viral infection	1/19 (5.3%)	1	0/20 (0%)	0
Gastrointestinal disorders
Abdominal Strangulated Hernia	0/19 (0%)	0	2/20 (10%)	2
Cardiac failure congestive	0/19 (0%)	0	1/20 (5%)	1
Abdominal pain	0/19 (0%)	0	1/20 (5%)	1
Infections and infestations
Apnoea	1/19 (5.3%)	1	0/20 (0%)	0
Convulsion	1/19 (5.3%)	1	1/20 (5%)	1
Pneumonia	0/19 (0%)	0	3/20 (15%)	3
Nervous system disorders
Corneal lesion	1/19 (5.3%)	1	0/20 (0%)	0
Intracranial pressure increased	0/19 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Headache	0/19 (0%)	0	1/20 (5%)	1
Ileus	0/19 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	rhASB		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/19 (100%)		20/20 (100%)
Blood and lymphatic system disorders
Anaemia	1/19 (5.3%)	1	3/20 (15%)	3
Iron deficiency anaemia	0/19 (0%)	0	1/20 (5%)	1
Splenomegaly	0/19 (0%)	0	2/20 (10%)	2
Cardiac disorders
Cardiac disorder	1/19 (5.3%)	1	0/20 (0%)	0
Cardiac failure	0/19 (0%)	0	1/20 (5%)	1
Cardiac valve disease	0/19 (0%)	0	2/20 (10%)	2
Cardiomegaly	0/19 (0%)	0	1/20 (5%)	1
Conduction disorder	1/19 (5.3%)	1	0/20 (0%)	0
Mitral valve stenosis	0/19 (0%)	0	1/20 (5%)	1
Tachycardia	1/19 (5.3%)	1	0/20 (0%)	0
Ventricular hypertrophy	0/19 (0%)	0	1/20 (5%)	1
Ear and labyrinth disorders
Cerumen impaction	1/19 (5.3%)	1	1/20 (5%)	1
Ear pain	8/19 (42.1%)	8	4/20 (20%)	4
Hearing impaired	2/19 (10.5%)	2	1/20 (5%)	1
Hypoacusis	1/19 (5.3%)	1	1/20 (5%)	1
Otorrhoea	2/19 (10.5%)	2	0/20 (0%)	0
Tympanic membrane hyperaemia	1/19 (5.3%)	1	1/20 (5%)	1
Eye disorders
Conjunctivitis	4/19 (21.1%)	4	0/20 (0%)	0
Corneal opacity	2/19 (10.5%)	2	0/20 (0%)	0
Eye discharge	0/19 (0%)	0	1/20 (5%)	1
Eye irritation	1/19 (5.3%)	1	1/20 (5%)	1
Eye pain	1/19 (5.3%)	1	1/20 (5%)	1
Eye pruritus	1/19 (5.3%)	1	0/20 (0%)	0
Eyelid oedema	0/19 (0%)	0	1/20 (5%)	1
Glaucoma	1/19 (5.3%)	1	1/20 (5%)	1
Keratoconjunctivitis sicca	0/19 (0%)	0	2/20 (10%)	2
Lacrimation increased	1/19 (5.3%)	1	0/20 (0%)	0
Visual acuity reduced	1/19 (5.3%)	1	2/20 (10%)	2
Gastrointestinal disorders
Abdominal distension	1/19 (5.3%)	1	2/20 (10%)	2
Abdominal pain	8/19 (42.1%)	8	6/20 (30%)	6
Abdominal pain lower	1/19 (5.3%)	1	0/20 (0%)	0
Abdominal pain upper	2/19 (10.5%)	2	0/20 (0%)	0
Abdominal strangulated hernia	0/19 (0%)	0	1/20 (5%)	1
Constipation	1/19 (5.3%)	1	2/20 (10%)	2
Diarrhea	3/19 (15.8%)	3	6/20 (30%)	6
Dysphagia	1/19 (5.3%)	1	0/20 (0%)	0
Flatulence	0/19 (0%)	0	1/20 (5%)	1
Gingivitis	0/19 (0%)	0	1/20 (5%)	1
Intestinal spasm	1/19 (5.3%)	1	0/20 (0%)	0
Nausea	4/19 (21.1%)	4	5/20 (25%)	5
Small intestinal obstruction	0/19 (0%)	0	1/20 (5%)	1
Tongue oedema	0/19 (0%)	0	1/20 (5%)	1
Tooth Disorder	0/19 (0%)	0	2/20 (10%)	2
Tooth discoloration	1/19 (5.3%)	1	0/20 (0%)	0
Umbilical hernia	2/19 (10.5%)	2	0/20 (0%)	0
Vomiting	6/19 (31.6%)	6	7/20 (35%)	7
General disorders
Anasarca	1/19 (5.3%)	1	0/20 (0%)	0
Application site erythema	1/19 (5.3%)	1	0/20 (0%)	0
Asthenia	0/19 (0%)	0	1/20 (5%)	1
Bloody discharge	0/19 (0%)	0	1/20 (5%)	1
Chest pain	3/19 (15.8%)	3	1/20 (5%)	1
Fatigue	2/19 (10.5%)	2	3/20 (15%)	3
Gait abnormal	0/19 (0%)	0	1/20 (5%)	1
Granuloma	0/19 (0%)	0	1/20 (5%)	1
Hernia pain	2/19 (10.5%)	2	3/20 (15%)	3
Hyperthermia	0/19 (0%)	0	1/20 (5%)	1
Influenza like illness	3/19 (15.8%)	3	3/20 (15%)	3
Infusion site pain	1/19 (5.3%)	1	2/20 (10%)	2
Localised oedema	1/19 (5.3%)	1	0/20 (0%)	0
Malaise	2/19 (10.5%)	2	0/20 (0%)	0
Mass	0/19 (0%)	0	1/20 (5%)	1
Oedema	0/19 (0%)	0	2/20 (10%)	2
Oedema peripheral	0/19 (0%)	0	1/20 (5%)	1
Pain	5/19 (26.3%)	5	1/20 (5%)	1
Pyrexia	8/19 (42.1%)	8	8/20 (40%)	8
Rigors	4/19 (21.1%)	4	0/20 (0%)	0
Suprapubic pain	0/19 (0%)	0	1/20 (5%)	1
Thirst	1/19 (5.3%)	1	0/20 (0%)	0
Hepatobiliary disorders
Hepatomegaly	0/19 (0%)	0	3/20 (15%)	3
Hepatosplenomegaly	0/19 (0%)	0	1/20 (5%)	1
Infections and infestations
Abscess oral	1/19 (5.3%)	1	0/20 (0%)	0
Acute tonsillitis	1/19 (5.3%)	1	0/20 (0%)	0
Bronchitis	0/19 (0%)	0	2/20 (10%)	2
Bronchopneumonia	1/19 (5.3%)	1	0/20 (0%)	0
Dental caries	0/19 (0%)	0	1/20 (5%)	1
Ear infection	2/19 (10.5%)	2	2/20 (10%)	2
Folliculitis	0/19 (0%)	0	1/20 (5%)	1
Fungal skin infection	0/19 (0%)	0	1/20 (5%)	1
Furuncle	1/19 (5.3%)	1	2/20 (10%)	2
Gastroenteritis	2/19 (10.5%)	2	0/20 (0%)	0
Hordeolum	1/19 (5.3%)	1	2/20 (10%)	2
Infection	0/19 (0%)	0	1/20 (5%)	1
Lower respiratory tract infection	0/19 (0%)	0	1/20 (5%)	1
Mastoiditis	1/19 (5.3%)	1	0/20 (0%)	0
Nasopharyngitis	1/19 (5.3%)	1	5/20 (25%)	5
Oral Candidiasis	0/19 (0%)	0	1/20 (5%)	1
Otitis externa	1/19 (5.3%)	1	0/20 (0%)	0
Otitis media	5/19 (26.3%)	5	4/20 (20%)	4
Otitis media acute	1/19 (5.3%)	1	0/20 (0%)	0
Pharyngitis	3/19 (15.8%)	3	1/20 (5%)	1
Pneumonia	0/19 (0%)	0	4/20 (20%)	4
Respiratory tract infection viral	1/19 (5.3%)	1	0/20 (0%)	0
Sinusitis	0/19 (0%)	0	4/20 (20%)	4
Tracheitis	0/19 (0%)	0	1/20 (5%)	1
Upper respiratory tract infection	4/19 (21.1%)	4	7/20 (35%)	7
Vaginitis	0/19 (0%)	0	1/20 (5%)	1
Injury, poisoning and procedural complications
Blister	0/19 (0%)	0	1/20 (5%)	1
Post procedural pain	1/19 (5.3%)	1	2/20 (10%)	2
Thermal burn	0/19 (0%)	0	1/20 (5%)	1
Investigations
Blood phosphorus increased	0/19 (0%)	0	1/20 (5%)	1
Blood pressure increased	0/19 (0%)	0	1/20 (5%)	1
Intraocular pressure increased	1/19 (5.3%)	1	0/20 (0%)	0
Oxygen saturation decreased	0/19 (0%)	0	1/20 (5%)	1
Sputum abnormal	1/19 (5.3%)	1	0/20 (0%)	0
Urine output decreased	0/19 (0%)	0	1/20 (5%)	1
Metabolism and nutrition disorders
Hypovolaemia	0/19 (0%)	0	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	8/19 (42.1%)	8	7/20 (35%)	7
Back pain	4/19 (21.1%)	4	4/20 (20%)	4
Hip deformity	0/19 (0%)	0	1/20 (5%)	1
Joint Stiffness	0/19 (0%)	0	1/20 (5%)	1
Muscle cramp	0/19 (0%)	0	1/20 (5%)	1
Myalgia	2/19 (10.5%)	2	1/20 (5%)	1
Neck pain	2/19 (10.5%)	2	3/20 (15%)	3
Pain in extremity	2/19 (10.5%)	2	8/20 (40%)	8
Nervous system disorders
Areflexia	2/19 (10.5%)	2	0/20 (0%)	0
Cervical myelopathy	0/19 (0%)	0	1/20 (5%)	1
Clonus	1/19 (5.3%)	1	0/20 (0%)	0
Convulsion	0/19 (0%)	0	1/20 (5%)	1
Dizziness	1/19 (5.3%)	1	1/20 (5%)	1
Epilepsy	1/19 (5.3%)	1	0/20 (0%)	0
Headache	8/19 (42.1%)	8	12/20 (60%)	12
Loss of consciousness	1/19 (5.3%)	1	0/20 (0%)	0
Migraine	1/19 (5.3%)	1	0/20 (0%)	0
Paraesthesia	1/19 (5.3%)	1	1/20 (5%)	1
Paresis	1/19 (5.3%)	1	2/20 (10%)	2
Sleep apnoea syndrome	1/19 (5.3%)	1	2/20 (10%)	2
Somnolence	0/19 (0%)	0	1/20 (5%)	1
Spinal cord compression	0/19 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Adjustment disorder	0/19 (0%)	0	1/20 (5%)	1
Agitation	0/19 (0%)	0	1/20 (5%)	1
Anxiety	1/19 (5.3%)	1	0/20 (0%)	0
Confusional state	1/19 (5.3%)	1	0/20 (0%)	0
Depression	1/19 (5.3%)	1	1/20 (5%)	1
Tic	0/19 (0%)	0	1/20 (5%)	1
Renal and urinary disorders
Bladder pain	0/19 (0%)	0	1/20 (5%)	1
Dysuria	1/19 (5.3%)	1	0/20 (0%)	0
Proteinuria	1/19 (5.3%)	1	0/20 (0%)	0
Urinary incontinence	1/19 (5.3%)	1	0/20 (0%)	0
Reproductive system and breast disorders
Hydrocele	0/19 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy	2/19 (10.5%)	2	1/20 (5%)	1
Asthma	0/19 (0%)	0	1/20 (5%)	1
Bronchial obstruction	0/19 (0%)	0	1/20 (5%)	1
Bronchospasm	1/19 (5.3%)	1	0/20 (0%)	0
Catarrh	1/19 (5.3%)	1	0/20 (0%)	0
Cough	5/19 (26.3%)	5	6/20 (30%)	6
Dyspnoea	4/19 (21.1%)	4	2/20 (10%)	2
Epistaxis	1/19 (5.3%)	1	0/20 (0%)	0
Hiccups	1/19 (5.3%)	1	0/20 (0%)	0
Nasal congestion	2/19 (10.5%)	2	0/20 (0%)	0
Obstructive airways disorder	1/19 (5.3%)	1	0/20 (0%)	0
Pharyngolaryngeal pain	1/19 (5.3%)	1	1/20 (5%)	1
Pulmonary hypertension	0/19 (0%)	0	1/20 (5%)	1
Respiratory distress	1/19 (5.3%)	1	0/20 (0%)	0
Restrictive pulmonary disease	2/19 (10.5%)	2	3/20 (15%)	3
Rhinitis	0/19 (0%)	0	1/20 (5%)	1
Rhinorrhoea	0/19 (0%)	0	4/20 (20%)	4
Sneezing	1/19 (5.3%)	1	0/20 (0%)	0
Tachypnoea	0/19 (0%)	0	1/20 (5%)	1
Throat irritation	0/19 (0%)	0	1/20 (5%)	1
Tonsillar hypertrophy	2/19 (10.5%)	2	1/20 (5%)	1
Wheezing	2/19 (10.5%)	2	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Acne	1/19 (5.3%)	1	0/20 (0%)	0
Alopecia	3/19 (15.8%)	3	3/20 (15%)	3
Eczema	1/19 (5.3%)	1	0/20 (0%)	0
Erythema	0/19 (0%)	0	1/20 (5%)	1
Exanthem	1/19 (5.3%)	1	0/20 (0%)	0
Face oedema	2/19 (10.5%)	2	0/20 (0%)	0
Nail discolouration	1/19 (5.3%)	1	0/20 (0%)	0
Pruritus	3/19 (15.8%)	3	3/20 (15%)	3
Rash	3/19 (15.8%)	3	2/20 (10%)	2
Skin reaction	0/19 (0%)	0	1/20 (5%)	1
Urticaria	1/19 (5.3%)	1	0/20 (0%)	0
Vascular disorders
Haematoma	1/19 (5.3%)	1	0/20 (0%)	0
Hyperaemia	0/19 (0%)	0	1/20 (5%)	1
Hypertension	2/19 (10.5%)	2	0/20 (0%)	0
Hypotension	1/19 (5.3%)	1	1/20 (5%)	1
Peripheral coldness	0/19 (0%)	0	1/20 (5%)	1
Petechiae	1/19 (5.3%)	1	0/20 (0%)	0
Poor venous access	1/19 (5.3%)	1	3/20 (15%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first publication of the results shall be made by Sponsor in a joint publication. If such a multi-center publication is not submitted within 12 months after conclusion of the study, the PI may publish the results from their site individually, subject however to comply with the other terms of the agreement.