Extension Study of Iron Chelation Therapy With Deferasirox in β-thalassemia and Rare Chronic Anemia Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00303329
• Collaborator: (none)
• Enrollment: 184
• Locations: 28
• Arm: 1
• Duration (Months): 55
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A 1-year randomized Phase II core trial was conducted to investigate the efficacy of deferasirox in regularly transfused patients with β-thalassemia and other rare chronic anemia 2 years of age and older. Patients who successfully completed the main trial may continue in the extension trial to receive chelation therapy with deferasirox for up to 3 years. Extension was prolonged to 4 years.

The objective of this study is to assess the long-term safety and efficacy of deferasirox in these patient groups.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Hemosiderosis	Drug: Deferasirox	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 184 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Extension Study of Iron Chelation Therapy With Deferasirox in β-thalassemia and Other Patients With Rare Chronic Anemia and Transfusional Iron Overload
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox Deferasirox daily oral dose between 5-40 mg/kg/day	Drug: Deferasirox; Deferasirox available as 125 mg, 250 mg or 500 mg tablets; Other Names: ICL670

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths [Core study Baseline to the end of the study (up to 60 months)]

   Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.

Secondary Outcome Measures

1. The Change in Liver Iron Content (LIC) as Assessed by Liver Biopsy at Baseline to the End of the Study [Core study Baseline to end of extension study (up to 60 months)]

   Liver iron concentration was monitored at the start of the core study, the end of the core study, and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant.

2. The Absolute Change in Liver Iron Content (LIC) as Assessed by Superconducting Quantum Interference Device (SQUID) From Baseline to End of Study [Core study Baseline to end of extension study (up to 60 months)]

   Liver iron concentration was monitored at the end of the core study and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant. Pediatric participants or participants with a medical contraindication to liver biopsy were allowed the use of SQUID in the extension study.

3. The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study [Core study Baseline to end of extension study (up to 60 months)]

   Serum ferritin was monitored monthly and the dose of deferasirox was increased or decreased in steps of 5 to 10 mg/kg/day up to a maximum of 40 mg/kg/day if appropriate, every 3 months. If serum ferritin fell to 500 ng/mL or lower on two consecutive study visits, an interruption of treatment until serum ferritin was more than 500 ng/mL was considered.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients completed the planned 12-month core study

• Female patients who have reached menarche and who are sexually active must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation

• Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with the national legislation

Exclusion Criteria:

• Pregnant or breast feeding patients

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital and Research center at Oakland	Oakland	California	United States	94609-1809
2	Stanford Hospital	Stanford	California	United States	94305
3	Childres's Hospital Boston	Boston	Massachusetts	United States	02115
4	New York Presbyterian Hospital	New York	New York	United States	10021
5	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-4399
6	Novartis Investigative Site	Brugge		Belgium
7	Novartis Investigative Site	Bruxelles		Belgium
8	Novartis Investigative Site	Gent		Belgium
9	Novartis Investigative Site	La Louvière		Belgium
10	Novartis Investigative Site	Leuven		Belgium
11	Novartis Investigative Site	Montreal		Canada
12	Novartis Investigative Site	Toronto		Canada
13	Novartis Investigative Site	Creteil		France
14	Novartis Investigative Site	Le Kremlin Bicetre		France
15	Novartis Investigative Site	Lille		France
16	Novartis Investigative Site	Troyes		France
17	Novartis Investigative Site	Duesseldorf		Germany
18	Novartis Investigative Site	Hannover		Germany
19	Novartis Investigative Site	Ulm		Germany
20	Novartis Investigative Site	Bologna		Italy
21	Novartis Investigative Site	Brindisi		Italy
22	Novartis Investigative Site	Cagliari		Italy
23	Novartis Investigative Site	Genova		Italy
24	Novartis Investigative Site	Milan		Italy
25	Novartis Investigative Site	Pavia		Italy
26	Novartis Investigative Site	Rome		Italy
27	Novartis Investigative Site	Torino		Italy
28	Novartis Investigative Site	London		United Kingdom

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00303329
• Other Study ID Numbers: CICL670A0108E1
• First Posted: Mar 16, 2006
• Last Update Posted: May 9, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: β-thalassemia; rare chronic anemia; iron overload; deferasirox; chronic anemias; transfusional hemosiderosis
• Additional relevant MeSH terms: Anemia; Thalassemia; beta-Thalassemia; Hemochromatosis; Hemosiderosis; Deferasirox

Study Results

Participant Flow

Arm/Group Title	β-thalassemia Patients	Rare Anemias Patients
Arm/Group Description	Deferasirox (5-40 mg/kg/day)	Deferasirox (5-40 mg/kg/day)
Period Title: Overall Study
STARTED	85	99
COMPLETED	50	37
NOT COMPLETED	35	62

Baseline Characteristics

Arm/Group Title	β-thalassemia Patients	Rare Anemias Patients	Total
Arm/Group Description	Deferasirox (5-40 mg/kg/day)	Deferasirox (5-40 mg/kg/day)	Total of all reporting groups
Overall Participants	85	99	184
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.7 (10.03)	43.7 (26.13)	35.0 (22.4)
Age, Customized (participants) [Number]
<6 years	2 2.4%	9 9.1%	11 6%
Between 6 and 11 years	5 5.9%	6 6.1%	11 6%
Between 12 and 15 years	8 9.4%	5 5.1%	13 7.1%
Between 16 and 49 years	69 81.2%	30 30.3%	99 53.8%
Between 50 and 64 years	1 1.2%	19 19.2%	20 10.9%
>=65 years	0 0%	30 30.3%	30 16.3%
Sex: Female, Male (Count of Participants)
Female	43 50.6%	48 48.5%	91 49.5%
Male	42 49.4%	51 51.5%	93 50.5%
Region of Enrollment (participants) [Number]
United States	15 17.6%	21 21.2%	36 19.6%
France	9 10.6%	11 11.1%	20 10.9%
Canada	12 14.1%	6 6.1%	18 9.8%
Belgium	4 4.7%	12 12.1%	16 8.7%
Germany	2 2.4%	23 23.2%	25 13.6%
United Kingdom	12 14.1%	0 0%	12 6.5%
Italy	31 36.5%	26 26.3%	57 31%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths
Description	Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Time Frame	Core study Baseline to the end of the study (up to 60 months)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised all participants who received at least one dose of deferasirox during either the core or extension studies.

Arm/Group Title	β-thalassemia Patients	Rare Anemias Patients
Arm/Group Description	Deferasirox (5-40 mg/kg/day)	Deferasirox (5-40 mg/kg/day)
Measure Participants	85	99
Adverse Events	85 100%	99 100%
Serious Adverse Events	36 42.4%	50 50.5%
Deaths	2 2.4%	12 12.1%

2. Secondary Outcome

Title	The Change in Liver Iron Content (LIC) as Assessed by Liver Biopsy at Baseline to the End of the Study
Description	Liver iron concentration was monitored at the start of the core study, the end of the core study, and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant.
Time Frame	Core study Baseline to end of extension study (up to 60 months)

Outcome Measure Data

Analysis Population Description

The full analysis Set (FAS) comprised all participants who received at least one dose of deferasirox during either the core or extension studies.

Arm/Group Title	β-thalassemia Patients	Rare Anemias Patients
Arm/Group Description	Deferasirox (5-40 mg/kg/day)	Deferasirox (5-40 mg/kg/day)
Measure Participants	55	42
Mean (Standard Deviation) [mg Fe/g dw]	-5.17 (11.659)	-5.10 (7.756)

3. Secondary Outcome

Title	The Absolute Change in Liver Iron Content (LIC) as Assessed by Superconducting Quantum Interference Device (SQUID) From Baseline to End of Study
Description	Liver iron concentration was monitored at the end of the core study and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant. Pediatric participants or participants with a medical contraindication to liver biopsy were allowed the use of SQUID in the extension study.
Time Frame	Core study Baseline to end of extension study (up to 60 months)

Outcome Measure Data

Analysis Population Description

The FAS comprised all participants who received at least one dose of deferasirox during either the core or extension studies.

Arm/Group Title	β-thalassemia Patients	Rare Anemias Patients
Arm/Group Description	Deferasirox (5-40 mg/kg/day)	Deferasirox (5-40 mg/kg/day)
Measure Participants	15	33
Mean (Standard Deviation) [mg Fe/g dw]	0.19 (8.577)	-2.04 (4.521)

4. Secondary Outcome

Title	The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study
Description	Serum ferritin was monitored monthly and the dose of deferasirox was increased or decreased in steps of 5 to 10 mg/kg/day up to a maximum of 40 mg/kg/day if appropriate, every 3 months. If serum ferritin fell to 500 ng/mL or lower on two consecutive study visits, an interruption of treatment until serum ferritin was more than 500 ng/mL was considered.
Time Frame	Core study Baseline to end of extension study (up to 60 months)

Outcome Measure Data

Analysis Population Description

The FAS comprised all participants who received at least one dose of deferasirox during either the core or extension studies.

Arm/Group Title	β-thalassemia Patients	Rare Anemias Patients
Arm/Group Description	Deferasirox (5-40 mg/kg/day)	Deferasirox (5-40 mg/kg/day)
Measure Participants	85	96
Baseline	4320.6 (2881.08)	3268.8 (2082.60)
End of Study	3708.2 (3018.10)	2896.0 (2597.22)
Absolute Change	-612.4 (2520.87)	-382.2 (2325.41)

Adverse Events

Arm/Group Title	Beta-thalassemia		Rare Anemias
Arm/Group Description	Deferasirox (5-40 mg/kg/day)		Deferasirox (5-40 mg/kg/day)
All Cause Mortality
	Beta-thalassemia		Rare Anemias
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Beta-thalassemia		Rare Anemias
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/85 (42.4%)		50/99 (50.5%)
Blood and lymphatic system disorders
Anaemia	0/85 (0%)		5/99 (5.1%)
Disseminated intravascular coagulation	0/85 (0%)		1/99 (1%)
Extramedullary haemopoiesis	1/85 (1.2%)		0/99 (0%)
Febrile neutropenia	0/85 (0%)		2/99 (2%)
Haemolysis	0/85 (0%)		1/99 (1%)
Lymphadenopathy	2/85 (2.4%)		0/99 (0%)
Neutropenia	0/85 (0%)		2/99 (2%)
Pancytopenia	0/85 (0%)		1/99 (1%)
Thrombocytopenia	0/85 (0%)		1/99 (1%)
Cardiac disorders
Angina pectoris	0/85 (0%)		1/99 (1%)
Arrhythmia	1/85 (1.2%)		1/99 (1%)
Atrial fibrillation	3/85 (3.5%)		1/99 (1%)
Cardiac arrest	0/85 (0%)		1/99 (1%)
Cardiac disorder	0/85 (0%)		1/99 (1%)
Cardiac failure	1/85 (1.2%)		0/99 (0%)
Cardiac failure congestive	2/85 (2.4%)		0/99 (0%)
Cardio-respiratory arrest	0/85 (0%)		1/99 (1%)
Cardiogenic shock	0/85 (0%)		1/99 (1%)
Cardiomyopathy	0/85 (0%)		1/99 (1%)
Left ventricular failure	1/85 (1.2%)		0/99 (0%)
Mitral valve incompetence	0/85 (0%)		1/99 (1%)
Palpitations	1/85 (1.2%)		0/99 (0%)
Tachyarrhythmia	1/85 (1.2%)		0/99 (0%)
Ventricular fibrillation	0/85 (0%)		1/99 (1%)
Ventricular tachyarrhythmia	1/85 (1.2%)		0/99 (0%)
Ear and labyrinth disorders
Sudden hearing loss	0/85 (0%)		1/99 (1%)
Tympanic membrane perforation	0/85 (0%)		1/99 (1%)
Endocrine disorders
Primary hypogonadism	0/85 (0%)		1/99 (1%)
Eye disorders
Cataract	0/85 (0%)		2/99 (2%)
Gastrointestinal disorders
Abdominal pain	3/85 (3.5%)		4/99 (4%)
Constipation	0/85 (0%)		2/99 (2%)
Gastrointestinal haemorrhage	0/85 (0%)		2/99 (2%)
Ileus	0/85 (0%)		1/99 (1%)
Melaena	1/85 (1.2%)		1/99 (1%)
Nausea	2/85 (2.4%)		0/99 (0%)
Varices oesophageal	0/85 (0%)		1/99 (1%)
Vomiting	3/85 (3.5%)		1/99 (1%)
General disorders
Catheter related complication	0/85 (0%)		1/99 (1%)
Chest pain	2/85 (2.4%)		1/99 (1%)
Chills	0/85 (0%)		2/99 (2%)
Drug withdrawal syndrome	1/85 (1.2%)		0/99 (0%)
General physical health deterioration	0/85 (0%)		1/99 (1%)
Hyperpyrexia	1/85 (1.2%)		0/99 (0%)
Malaise	0/85 (0%)		1/99 (1%)
Oedema	1/85 (1.2%)		0/99 (0%)
Pyrexia	3/85 (3.5%)		12/99 (12.1%)
Hepatobiliary disorders
Bile duct stone	1/85 (1.2%)		0/99 (0%)
Cholelithiasis	1/85 (1.2%)		0/99 (0%)
Cholelithiasis obstructive	1/85 (1.2%)		0/99 (0%)
Gallbladder disorder	1/85 (1.2%)		0/99 (0%)
Hepatic failure	1/85 (1.2%)		0/99 (0%)
Hepatic haemorrhage	0/85 (0%)		1/99 (1%)
Hepatitis	0/85 (0%)		2/99 (2%)
Infections and infestations
Abdominal infection	0/85 (0%)		1/99 (1%)
Anal abscess	0/85 (0%)		1/99 (1%)
Arthritis infective	0/85 (0%)		1/99 (1%)
Bacteraemia	0/85 (0%)		1/99 (1%)
Bacterial sepsis	0/85 (0%)		2/99 (2%)
Bronchiolitis	0/85 (0%)		1/99 (1%)
Bronchitis	0/85 (0%)		1/99 (1%)
Bronchopulmonary aspergillosis	0/85 (0%)		1/99 (1%)
Catheter related infection	0/85 (0%)		1/99 (1%)
Erysipelas	0/85 (0%)		1/99 (1%)
Gastroenteritis	2/85 (2.4%)		1/99 (1%)
Gastroenteritis yersinia	0/85 (0%)		1/99 (1%)
Haematoma infection	0/85 (0%)		1/99 (1%)
Hepatitis A	0/85 (0%)		1/99 (1%)
Infection	0/85 (0%)		1/99 (1%)
Influenza	1/85 (1.2%)		1/99 (1%)
Klebsiella infection	0/85 (0%)		1/99 (1%)
Klebsiella sepsis	0/85 (0%)		1/99 (1%)
Lobar pneumonia	0/85 (0%)		1/99 (1%)
Lower respiratory tract infection	0/85 (0%)		2/99 (2%)
Lung infection	0/85 (0%)		2/99 (2%)
Meningitis viral	0/85 (0%)		1/99 (1%)
Neutropenic sepsis	0/85 (0%)		1/99 (1%)
Orchitis	1/85 (1.2%)		0/99 (0%)
Peridiverticular abscess	0/85 (0%)		1/99 (1%)
Pharyngitis	0/85 (0%)		1/99 (1%)
Pharyngitis streptococcal	1/85 (1.2%)		0/99 (0%)
Pneumonia	0/85 (0%)		5/99 (5.1%)
Pseudomonal sepsis	0/85 (0%)		1/99 (1%)
Pyelonephritis	0/85 (0%)		1/99 (1%)
Sepsis	0/85 (0%)		5/99 (5.1%)
Septic shock	0/85 (0%)		3/99 (3%)
Staphylococcal sepsis	0/85 (0%)		1/99 (1%)
Subcutaneous abscess	0/85 (0%)		1/99 (1%)
Upper respiratory tract infection	0/85 (0%)		1/99 (1%)
Urosepsis	0/85 (0%)		1/99 (1%)
Viral infection	1/85 (1.2%)		1/99 (1%)
Injury, poisoning and procedural complications
Clavicle fracture	1/85 (1.2%)		0/99 (0%)
Contusion	1/85 (1.2%)		0/99 (0%)
Device failure	0/85 (0%)		1/99 (1%)
Facial bones fracture	0/85 (0%)		1/99 (1%)
Fall	1/85 (1.2%)		0/99 (0%)
Fibula fracture	0/85 (0%)		1/99 (1%)
Forearm fracture	1/85 (1.2%)		0/99 (0%)
Head injury	1/85 (1.2%)		0/99 (0%)
Hepatic haematoma	0/85 (0%)		1/99 (1%)
Radius fracture	1/85 (1.2%)		0/99 (0%)
Rib fracture	0/85 (0%)		1/99 (1%)
Road traffic accident	0/85 (0%)		1/99 (1%)
Skin laceration	0/85 (0%)		1/99 (1%)
Spinal fracture	1/85 (1.2%)		1/99 (1%)
Splenic rupture	1/85 (1.2%)		0/99 (0%)
Subdural haematoma	0/85 (0%)		1/99 (1%)
Tibia fracture	0/85 (0%)		1/99 (1%)
Transfusion reaction	0/85 (0%)		1/99 (1%)
Investigations
Blood phosphorus increased	0/85 (0%)		1/99 (1%)
Electrocardiogram abnormal	0/85 (0%)		1/99 (1%)
Neutrophil count decreased	0/85 (0%)		1/99 (1%)
Transaminases increased	1/85 (1.2%)		2/99 (2%)
Metabolism and nutrition disorders
Anorexia	0/85 (0%)		2/99 (2%)
Dehydration	0/85 (0%)		1/99 (1%)
Hyperglycaemia	1/85 (1.2%)		0/99 (0%)
Hypocalcaemia	1/85 (1.2%)		0/99 (0%)
Hypoglycaemia	0/85 (0%)		1/99 (1%)
Hypoglycaemic seizure	0/85 (0%)		1/99 (1%)
Hypokalaemia	0/85 (0%)		1/99 (1%)
Hypophosphataemia	0/85 (0%)		1/99 (1%)
Type 1 diabetes mellitus	1/85 (1.2%)		0/99 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/85 (1.2%)		0/99 (0%)
Back pain	1/85 (1.2%)		1/99 (1%)
Bone cyst	1/85 (1.2%)		0/99 (0%)
Knee deformity	2/85 (2.4%)		0/99 (0%)
Musculoskeletal chest pain	1/85 (1.2%)		0/99 (0%)
Musculoskeletal pain	0/85 (0%)		1/99 (1%)
Myalgia	1/85 (1.2%)		0/99 (0%)
Osteoarthritis	0/85 (0%)		1/99 (1%)
Pain in extremity	1/85 (1.2%)		0/99 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia	0/85 (0%)		2/99 (2%)
Myelodysplastic syndrome	0/85 (0%)		1/99 (1%)
Nervous system disorders
Cerebral haemorrhage	0/85 (0%)		2/99 (2%)
Coma	0/85 (0%)		1/99 (1%)
Dementia	0/85 (0%)		1/99 (1%)
Dizziness	1/85 (1.2%)		0/99 (0%)
Encephalitis	0/85 (0%)		1/99 (1%)
Headache	1/85 (1.2%)		0/99 (0%)
Hypokinesia	1/85 (1.2%)		0/99 (0%)
Loss of consciousness	0/85 (0%)		1/99 (1%)
Migraine	0/85 (0%)		1/99 (1%)
Psychomotor hyperactivity	0/85 (0%)		1/99 (1%)
Sciatica	1/85 (1.2%)		0/99 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/85 (1.2%)		0/99 (0%)
Psychiatric disorders
Adjustment disorder	0/85 (0%)		1/99 (1%)
Anxiety	2/85 (2.4%)		0/99 (0%)
Delirium	1/85 (1.2%)		0/99 (0%)
Depression	1/85 (1.2%)		3/99 (3%)
Illusion	1/85 (1.2%)		0/99 (0%)
Mental disorder	0/85 (0%)		1/99 (1%)
Suicidal ideation	0/85 (0%)		1/99 (1%)
Suicide attempt	0/85 (0%)		1/99 (1%)
Renal and urinary disorders
Anuria	1/85 (1.2%)		0/99 (0%)
Calculus bladder	1/85 (1.2%)		0/99 (0%)
Calculus ureteric	0/85 (0%)		1/99 (1%)
Nephrolithiasis	0/85 (0%)		1/99 (1%)
Renal colic	1/85 (1.2%)		0/99 (0%)
Renal mass	1/85 (1.2%)		0/99 (0%)
Urethral haemorrhage	0/85 (0%)		1/99 (1%)
Reproductive system and breast disorders
Testicular disorder	0/85 (0%)		1/99 (1%)
Testicular torsion	0/85 (0%)		1/99 (1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/85 (0%)		1/99 (1%)
Dyspnoea	0/85 (0%)		2/99 (2%)
Epistaxis	1/85 (1.2%)		0/99 (0%)
Hypoxia	0/85 (0%)		1/99 (1%)
Nasal congestion	1/85 (1.2%)		0/99 (0%)
Pharyngeal haemorrhage	0/85 (0%)		1/99 (1%)
Pleurisy	0/85 (0%)		1/99 (1%)
Pneumonitis	0/85 (0%)		1/99 (1%)
Pulmonary haemorrhage	0/85 (0%)		1/99 (1%)
Respiratory failure	0/85 (0%)		1/99 (1%)
Tonsillar hypertrophy	1/85 (1.2%)		0/99 (0%)
Skin and subcutaneous tissue disorders
Rash	1/85 (1.2%)		0/99 (0%)
Stasis dermatitis	0/85 (0%)		1/99 (1%)
Surgical and medical procedures
Toe amputation	0/85 (0%)		1/99 (1%)
Vascular disorders
Hypotension	1/85 (1.2%)		1/99 (1%)
Hypovolaemic shock	0/85 (0%)		1/99 (1%)
Poor venous access	0/85 (0%)		1/99 (1%)
Other (Not Including Serious) Adverse Events
	Beta-thalassemia		Rare Anemias
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/85 (98.8%)		96/99 (97%)
Blood and lymphatic system disorders
Lymphadenopathy	5/85 (5.9%)		1/99 (1%)
Cardiac disorders
Palpitations	12/85 (14.1%)		8/99 (8.1%)
Tachycardia	12/85 (14.1%)		6/99 (6.1%)
Ear and labyrinth disorders
Ear pain	10/85 (11.8%)		6/99 (6.1%)
Tinnitus	6/85 (7.1%)		0/99 (0%)
Vertigo	6/85 (7.1%)		6/99 (6.1%)
Eye disorders
Vision blurred	5/85 (5.9%)		1/99 (1%)
Gastrointestinal disorders
Abdominal discomfort	7/85 (8.2%)		3/99 (3%)
Abdominal distension	10/85 (11.8%)		5/99 (5.1%)
Abdominal pain	32/85 (37.6%)		31/99 (31.3%)
Abdominal pain upper	30/85 (35.3%)		13/99 (13.1%)
Constipation	23/85 (27.1%)		14/99 (14.1%)
Diarrhoea	40/85 (47.1%)		50/99 (50.5%)
Dyspepsia	9/85 (10.6%)		7/99 (7.1%)
Gastritis	1/85 (1.2%)		7/99 (7.1%)
Gingival bleeding	1/85 (1.2%)		5/99 (5.1%)
Nausea	36/85 (42.4%)		34/99 (34.3%)
Toothache	12/85 (14.1%)		3/99 (3%)
Vomiting	23/85 (27.1%)		36/99 (36.4%)
General disorders
Asthenia	14/85 (16.5%)		19/99 (19.2%)
Chest pain	19/85 (22.4%)		9/99 (9.1%)
Fatigue	17/85 (20%)		18/99 (18.2%)
Influenza like illness	9/85 (10.6%)		4/99 (4%)
Malaise	5/85 (5.9%)		4/99 (4%)
Oedema	2/85 (2.4%)		8/99 (8.1%)
Oedema peripheral	7/85 (8.2%)		12/99 (12.1%)
Pyrexia	39/85 (45.9%)		36/99 (36.4%)
Hepatobiliary disorders
Hepatomegaly	4/85 (4.7%)		5/99 (5.1%)
Immune system disorders
Seasonal allergy	8/85 (9.4%)		6/99 (6.1%)
Infections and infestations
Bronchitis	9/85 (10.6%)		20/99 (20.2%)
Ear infection	7/85 (8.2%)		3/99 (3%)
Gastroenteritis	14/85 (16.5%)		17/99 (17.2%)
Influenza	14/85 (16.5%)		15/99 (15.2%)
Nasopharyngitis	33/85 (38.8%)		26/99 (26.3%)
Oral herpes	3/85 (3.5%)		8/99 (8.1%)
Otitis media	3/85 (3.5%)		6/99 (6.1%)
Pharyngitis	26/85 (30.6%)		4/99 (4%)
Rhinitis	21/85 (24.7%)		12/99 (12.1%)
Sinusitis	3/85 (3.5%)		6/99 (6.1%)
Tonsillitis	9/85 (10.6%)		8/99 (8.1%)
Tooth abscess	7/85 (8.2%)		1/99 (1%)
Tooth infection	7/85 (8.2%)		2/99 (2%)
Upper respiratory tract infection	23/85 (27.1%)		16/99 (16.2%)
Urinary tract infection	10/85 (11.8%)		10/99 (10.1%)
Viral infection	5/85 (5.9%)		2/99 (2%)
Viral upper respiratory tract infection	10/85 (11.8%)		1/99 (1%)
Injury, poisoning and procedural complications
Fall	5/85 (5.9%)		3/99 (3%)
Procedural pain	14/85 (16.5%)		3/99 (3%)
Transfusion reaction	13/85 (15.3%)		13/99 (13.1%)
Investigations
Blood creatinine increased	16/85 (18.8%)		19/99 (19.2%)
Cardiac murmur	5/85 (5.9%)		5/99 (5.1%)
Transaminases increased	3/85 (3.5%)		5/99 (5.1%)
Weight decreased	2/85 (2.4%)		5/99 (5.1%)
Metabolism and nutrition disorders
Anorexia	7/85 (8.2%)		7/99 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	18/85 (21.2%)		12/99 (12.1%)
Back pain	32/85 (37.6%)		20/99 (20.2%)
Bone pain	8/85 (9.4%)		10/99 (10.1%)
Muscle spasms	10/85 (11.8%)		9/99 (9.1%)
Musculoskeletal pain	9/85 (10.6%)		2/99 (2%)
Neck pain	8/85 (9.4%)		2/99 (2%)
Pain in extremity	17/85 (20%)		9/99 (9.1%)
Nervous system disorders
Dizziness	5/85 (5.9%)		8/99 (8.1%)
Headache	45/85 (52.9%)		34/99 (34.3%)
Paraesthesia	5/85 (5.9%)		1/99 (1%)
Psychiatric disorders
Anxiety	6/85 (7.1%)		4/99 (4%)
Depression	11/85 (12.9%)		8/99 (8.1%)
Insomnia	8/85 (9.4%)		7/99 (7.1%)
Renal and urinary disorders
Dysuria	7/85 (8.2%)		3/99 (3%)
Proteinuria	5/85 (5.9%)		3/99 (3%)
Renal failure	0/85 (0%)		6/99 (6.1%)
Reproductive system and breast disorders
Dysmenorrhoea	6/85 (7.1%)		2/99 (2%)
Respiratory, thoracic and mediastinal disorders
Cough	36/85 (42.4%)		34/99 (34.3%)
Dyspnoea	10/85 (11.8%)		12/99 (12.1%)
Epistaxis	2/85 (2.4%)		10/99 (10.1%)
Nasal congestion	9/85 (10.6%)		3/99 (3%)
Oropharyngeal pain	30/85 (35.3%)		15/99 (15.2%)
Productive cough	11/85 (12.9%)		1/99 (1%)
Rhinorrhoea	6/85 (7.1%)		3/99 (3%)
Skin and subcutaneous tissue disorders
Erythema	5/85 (5.9%)		3/99 (3%)
Pruritus	7/85 (8.2%)		9/99 (9.1%)
Rash	14/85 (16.5%)		13/99 (13.1%)
Rash pruritic	7/85 (8.2%)		1/99 (1%)
Vascular disorders
Haematoma	1/85 (1.2%)		5/99 (5.1%)
Hypertension	1/85 (1.2%)		7/99 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.