Hydroxyurea and Magnesium Pidolate to Treat People With Hemoglobin Sickle Cell Disease

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00532883
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 44
• Locations: 19
• Arms: 4
• Duration (Months): 31
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause intense pain episodes. Hemoglobin SCD (HbSC) is a form of SCD that is characterized by dense red blood cells. The purpose of this study is to evaluate the safety and effectiveness of hydroxyurea and magnesium pidolate, alone and combined, at reducing red blood cell density and the frequency of pain episodes in people with HbSC.

Condition or Disease	Intervention/Treatment	Phase
Hemoglobin SC Disease	Drug: Hydroxyurea; Drug: Magnesium Pidolate; Other: Placebo Pills and Placebo Liquid	Phase 2

Detailed Description

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." SCD is caused by an abnormal type of hemoglobin, which is a protein inside red blood cells that carries oxygen. HbSC is a form of SCD that is characterized by the presence of dense red blood cells. People with HbSC usually develop less severe SCD symptoms than people with the more common form of the disease. There are limited treatment approaches aimed specifically at modifying the abnormal state of red blood cells. Also, few combination therapy treatments have been studied. The medication hydroxyurea is currently used to prevent sickle cell crises and to decrease the need for blood transfusions. The dietary supplement magnesium has not been widely studied as a treatment for SCD, but it may prevent dehydration, which may decrease the frequency of sickle cell crises. The purpose of this study is to evaluate the safety and effectiveness of hydroxyurea and magnesium pidolate, alone and combined, at reducing red blood cell density and the frequency of sickle cell crises in people with HbSC.

This 1-year study will enroll people with HbSC. Participants will be randomly assigned to one of the following four treatment groups:

• Group 1 participants will receive placebo pills and placebo liquid.

• Group 2 participants will receive hydroxyurea pills and placebo liquid.

• Group 3 participants will receive placebo pills and magnesium pidolate liquid.

• Group 4 participants will receive hydroxyurea pills and magnesium pidolate liquid.

Participants will receive the hydroxyurea or placebo pills once a day and the magnesium pidolate or placebo liquid twice a day for 11 months. Study visits will occur every 2 weeks during the first 2 months of the study, once a month for the following 9 months, and then at Year 1. At each visit, a physical exam and blood collection will occur. Selected visits will also include urine collection and a pregnancy test for female participants. Throughout the study, participants will record their study medication use in a daily diary.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effectiveness of Hydroxyurea and Magnesium Pidolate Alone and in Combination in Hemoglobin SC Disease: A Phase II Trial
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Pills and Placebo Liquid	Other: Placebo Pills and Placebo Liquid; HU/Placebo capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)
Active Comparator: Hydroxyurea Pills and Placebo Liquid	Drug: Hydroxyurea; HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months)
Active Comparator: Placebo Pills and Magnesium Pidolate Liquid	Drug: Magnesium Pidolate; HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)
Active Comparator: Hydroxyurea Pills and Magnesium Pidolate Liquid	Drug: Hydroxyurea; HU capsules (20 mg/kg/day for 11 months) Mg/Placebo liquid (0.6 mEq/kg/day for 11 months); Drug: Magnesium Pidolate; HU/Placebo capsules (20 mg/kg/day for 11 months) Mg liquid (0.6 mEq/kg/day for 11 months)

Outcome Measures

Primary Outcome Measures

1. Distribution of the Density of Hemoglobin SC Red Cells [measured 2 months after initiation of treatment]

   An individuals' percentage of red blood cells with density greater than 41 g/dL as measured by Advia.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of HbSC disease

• Hemoglobin level between 8 and 12.5 g/dL

• At least one vaso-occlusive event (e.g., pain, acute chest syndrome) in the 12 months prior to study entry. An episode of pain is defined as the occurrence of pain in the extremities, back, abdomen, chest, or head that lasts at least 2 hours; requires a visit to a hospital, emergency room, clinic, or provider's office; and is not explained except by SCD. Acute chest syndrome is defined as a new pulmonary infiltrate on a chest x-ray associated with a fever (greater than 38.5° C), tachypnea, wheezing, cough, or chest pain.

• Regular compliance with comprehensive care

• In a steady disease state and not experiencing an acute complication of SCD (i.e., no hospitalization, pain event, or episode of acute chest syndrome within the 1 month prior to study entry)

Exclusion Criteria:

• Previous transfusion with remaining hemoglobin A greater than 10%

• Previous treatment with hydroxyurea within the last 3 months

• Previous treatment with magnesium within the 3 months prior to study entry (including vitamins containing magnesium)

• Poor compliance with previous treatment regimens

• Liver dysfunction (SGPT greater than twice the upper limit of normal) within the 1 month prior to study entry

• Kidney dysfunction (creatinine greater than or equal to 1.0 mg/dL for participants less than 18 years of age; greater than or equal to 1.2 mg/dL for participants 18 years of age or older) within the 1 month prior to study entry

• Pregnant

• Ten or more hospital admissions for pain in the 12 months prior to study entry

• Daily use of narcotics

• Treatment with any investigational drug in the 3 months prior to study entry

• Less than 3% red blood cells with density greater than 41 g/dL (as measured by the ADVIA 120 system)

• Positive HIV test

• Other long-term illness or disorder other than SCD that could adversely affect performance in the study (e.g., tuberculosis)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Children's Hospital and Research Center	Oakland	California	United States	94609-1809
3	University of California Davis	Sacramento	California	United States	95817
4	University of Colorado	Aurora	Colorado	United States	80045
5	University of Miami	Miami	Florida	United States	33136
6	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30342-1600
7	University of Louisville	Louisville	Kentucky	United States	40202
8	Johns Hopkins University	Baltimore	Maryland	United States	21205
9	Boston Medical Center	Boston	Massachusetts	United States	02118
10	Children's Hospital Boston	Boston	Massachusetts	United States	02118
11	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
12	Montefiore Medical Center	Bronx	New York	United States	10463
13	Duke University Medical Center	Durham	North Carolina	United States	27710
14	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
15	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
16	Saint Christopher's Hospital	Philadelphia	Pennsylvania	United States	19134-1095
17	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19444
18	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
19	Children's Medical Center	Dallas	Texas	United States	75235

Sponsors and Collaborators

• St. Jude Children's Research Hospital
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Winfred C. Wang, MD, St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00532883
• Other Study ID Numbers: CHAMPS-St. Jude; U54HL070587
• First Posted: Sep 21, 2007
• Last Update Posted: Jan 18, 2013
• Last Verified: Jan 1, 2010

• Keywords provided by St. Jude Children's Research Hospital: Sickle Cell Disease; Vaso-occlusive Event; Painful Crises; Acute Chest Syndrome
• Additional relevant MeSH terms: Hemoglobin SC Disease; Hydroxyurea

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from October 2006 through June 2008 at 10 sites across the United States. Subjects were recruited from sickle cell specific clinics.
Pre-assignment Detail	Subjects were screened to ensure specific laboratory measurement levels after enrollment but prior to randomization.

Arm/Group Title	Hydroxyurea/Magnesium	Hydroxyurea/Mg Placebo	HU Placebo/Magnesium	HU Placebo/Mg Placebo
Arm/Group Description	Hydroxyurea (20 mg/kg/day) combined with liquid magnesium pidolate (0.6 mEq/kg/day).	Hydroxyurea (20 mg/kg/day) combined with liquid Mg placebo.	HU placebo combined with liquid magnesium pidolate (0.6 mEq/kg/day).	Placebo for both hydroxyurea (20 mg/kg/day) and liquid magnesium pidolate (0.6 mEq/kg/day).
Period Title: Overall Study
STARTED	11	12	10	11
COMPLETED	5	5	6	6
NOT COMPLETED	6	7	4	5

Baseline Characteristics

Arm/Group Title	Hydroxyurea/Magnesium	Hydroxyurea/Mg Placebo	HU Placebo/Magnesium	HU Placebo/Mg Placebo	Total
Arm/Group Description	Hydroxyurea (20 mg/kg/day) combined with liquid magnesium pidolate (0.6 mEq/kg/day).	Hydroxyurea (20 mg/kg/day) combined with liquid Mg placebo.	HU placebo combined with liquid magnesium pidolate (0.6 mEq/kg/day).	Placebo for both hydroxyurea (20 mg/kg/day) and liquid magnesium pidolate (0.6 mEq/kg/day).	Total of all reporting groups
Overall Participants	11	12	10	11	44
Age (Count of Participants)
<=18 years	10 90.9%	9 75%	9 90%	9 81.8%	37 84.1%
Between 18 and 65 years	1 9.1%	3 25%	1 10%	2 18.2%	7 15.9%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.5 (4.41)	16.8 (12.6)	14.8 (8.45)	17.3 (12.41)	16.7 (9.81)
Sex: Female, Male (Count of Participants)
Female	4 36.4%	8 66.7%	3 30%	4 36.4%	19 43.2%
Male	7 63.6%	4 33.3%	7 70%	7 63.6%	25 56.8%
Region of Enrollment (participants) [Number]
United States	11 100%	12 100%	10 100%	11 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Distribution of the Density of Hemoglobin SC Red Cells
Description	An individuals' percentage of red blood cells with density greater than 41 g/dL as measured by Advia.
Time Frame	measured 2 months after initiation of treatment

Outcome Measure Data

Analysis Population Description

ITT: All randomized subjects who receive any clinical trial material. Subjects in the ITT population will be classified according to the treatment group to which they were randomized, regardless of what study drug they received.

Arm/Group Title	Hydroxyurea/Magnesium	Hydroxyurea/Mg Placebo	HU Placebo/Magnesium	HU Placebo/Mg Placebo
Arm/Group Description	Hydroxyurea (20 mg/kg/day) combined with liquid magnesium pidolate (0.6 mEq/kg/day).	Hydroxyurea (20 mg/kg/day) combined with liquid Mg placebo.	HU placebo combined with liquid magnesium pidolate (0.6 mEq/kg/day).	Placebo for both hydroxyurea (20 mg/kg/day) and liquid magnesium pidolate (0.6 mEq/kg/day).
Measure Participants	11	12	10	11
Mean (Standard Deviation) [percent of cells]	12.09 (5.075)	11.16 (7.296)	10.49 (4.572)	12.79 (3.739)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hydroxyurea/Magnesium, Hydroxyurea/Mg Placebo, HU Placebo/Magnesium, HU Placebo/Mg Placebo
	Comments	F-test from a longitudinal mixed model (controlling for baseline measurement)testing the hypothesis of no difference in mean percent dense cells between the four treatment groups at Visit 6. The study was originally powered to detect a difference of 20%, but it was stopped early.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments	This is a global test comparing all four treatment arms.
	Method	Mixed Models Analysis
	Comments

Adverse Events

Arm/Group Title	Hydroxyurea/Magnesium Pidolate		Hydroxyurea/Placebo		Placebo/Magnesium Pidolate		Placebo/Placebo
Arm/Group Description	20 mg/kg/day		0.6 mEq/kg/day		20 mg/kg/day HU + 0.6 mEq/kg/day Mg
All Cause Mortality
	Hydroxyurea/Magnesium Pidolate		Hydroxyurea/Placebo		Placebo/Magnesium Pidolate		Placebo/Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Hydroxyurea/Magnesium Pidolate		Hydroxyurea/Placebo		Placebo/Magnesium Pidolate		Placebo/Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		2/12 (16.7%)		3/10 (30%)		2/11 (18.2%)
Blood and lymphatic system disorders
Acute chest syndrome	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Anaemia	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis	3/11 (27.3%)	5	1/12 (8.3%)	3	3/10 (30%)	4	2/11 (18.2%)	3
General disorders
Pyrexia	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Infections and infestations
Cellulitis	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Pharyngitis streptococcal	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pneumonia	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Surgical and medical procedures
Skin graft	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Hydroxyurea/Magnesium Pidolate		Hydroxyurea/Placebo		Placebo/Magnesium Pidolate		Placebo/Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)		10/12 (83.3%)		9/10 (90%)		10/11 (90.9%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Neutropenia	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	1/11 (9.1%)	1
Splenomegaly	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis	6/11 (54.5%)	39	6/12 (50%)	18	4/10 (40%)	7	8/11 (72.7%)	32
Ear and labyrinth disorders
Ear pain	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	1/11 (9.1%)	1
Eye disorders
Conjunctivitis	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Eye pruritus	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Ocular hyperaemia	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Ocular icterus	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/11 (18.2%)	5	1/12 (8.3%)	2	0/10 (0%)	0	2/11 (18.2%)	3
Constipation	0/11 (0%)	0	1/12 (8.3%)	1	2/10 (20%)	2	1/11 (9.1%)	1
Diarrhoea	2/11 (18.2%)	2	2/12 (16.7%)	2	1/10 (10%)	2	2/11 (18.2%)	3
Dyspepsia	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Mouth ulceration	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Nausea	1/11 (9.1%)	1	2/12 (16.7%)	2	0/10 (0%)	0	0/11 (0%)	0
Oral soft tissue disorder	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Vomiting	1/11 (9.1%)	3	1/12 (8.3%)	2	3/10 (30%)	4	3/11 (27.3%)	4
General disorders
Influenza like illness	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Infusion site erythema	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Injection site pain	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Pain	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pyrexia	2/11 (18.2%)	3	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Immune system disorders
Hypersensitivity	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Multiple allergies	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Seasonal allergy	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Infections and infestations
Abscess	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Cellulitis	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Furuncle	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Infection	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Myringitis bullous	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Nasopharyngitis	1/11 (9.1%)	1	1/12 (8.3%)	1	1/10 (10%)	1	2/11 (18.2%)	2
Osteomyelitis	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Otitis media	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Sinusitis	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Upper respiratory tract infection	0/11 (0%)	0	1/12 (8.3%)	1	1/10 (10%)	2	2/11 (18.2%)	4
Urinary tract infection	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Viral infection	0/11 (0%)	0	1/12 (8.3%)	1	1/10 (10%)	1	0/11 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Head injury	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Joint injury	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Limb injury	2/11 (18.2%)	2	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Post procedural swelling	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Scratch	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Skin laceration	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2
Investigations
Arterial bruit	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Spleen palpable	0/11 (0%)	0	2/12 (16.7%)	3	0/10 (0%)	0	0/11 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Dehydration	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1
Back pain	2/11 (18.2%)	2	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Joint swelling	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Muscle spasms	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Musculoskeletal chest pain	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Osteonecrosis	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pain in jaw	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Nervous system disorders
Dysgeusia	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Headache	3/11 (27.3%)	10	5/12 (41.7%)	6	1/10 (10%)	1	3/11 (27.3%)	4
Migraine	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Psychiatric disorders
Anxiety	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Depression	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Reproductive system and breast disorders
Breast swelling	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Dysmenorrhoea	0/11 (0%)	0	2/12 (16.7%)	3	0/10 (0%)	0	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Cough	1/11 (9.1%)	1	0/12 (0%)	0	1/10 (10%)	1	2/11 (18.2%)	5
Dyspnoea exertional	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Epistaxis	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Nasal congestion	0/11 (0%)	0	0/12 (0%)	0	2/10 (20%)	2	1/11 (9.1%)	1
Pharyngolaryngeal pain	1/11 (9.1%)	1	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Rhinitis allergic	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Rhinorrhoea	1/11 (9.1%)	1	0/12 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1
Sneezing	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Dermatitis contact	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Nail disorder	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Pigmentation disorder	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Rash	2/11 (18.2%)	2	0/12 (0%)	0	2/10 (20%)	2	0/11 (0%)	0
Rash macular	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Rash papular	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Skin hyperpigmentation	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0	0/11 (0%)	0
Skin lesion	0/11 (0%)	0	1/12 (8.3%)	1	1/10 (10%)	1	1/11 (9.1%)	1
Swelling face	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1	0/11 (0%)	0

Limitations/Caveats

This study was stopped early due to slow enrollment. It should therefore be viewed as a pilot study.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.