HYPERION: Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01254227
• Collaborator: (none)
• Enrollment: 60
• Locations: 15
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of deferasirox in combination with deferoxamine followed be deferasirox monotherapy in patients with severe iron overload due to chronic blood transfusions.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Iron Overload	Drug: Deferasirox and Deferoxamine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Patients With Severe Cardiac Iron Overload Due to Chronic Blood Transfusion (HYPERION)
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox Deferoxamine combination followed by Deferasirox monotherapy	Drug: Deferasirox and Deferoxamine

Outcome Measures

Primary Outcome Measures

1. Change in Cardiac Iron Content From Baseline to Month 12 [From Baseline to Month 12]

   Cardiac T2* is the most sensitive and reproducible test in detecting myocardial iron load. A cardiac T2* value of <10 ms is defined as severe cardiac iron overload. Participants who do not have baseline T2* or do not have any post-baseline T2* are excluded from the analysis.

Secondary Outcome Measures

1. Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24 [From the Months 6, 12, 18 and 24]

   The number of evaluable participants at each visit were used as the denominator for the calculation of proportion at each visit.

2. Change in Cardiac Iron Content From Baseline to Month 6,18 and 24 [From Baseline to Months 6, 18 and 24]

   The change in cardiac iron content was calculated as ratio of Cardiac T2* at different time points; the efficacy endpoint analyses were performed on the Full Analysis Set (FAS).

3. Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24 [From the Months 6, 12, 18 and 24]

   Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.

4. Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24 [From the Months 6, 12, 18 and 24]

   Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.

5. Time to Achieve From Baseline (FAS) of at Least 10% at Month 24 [At 24 months]

   Time from date of start of study treatment to date when first achieving T2* ≥ 10 ms (but at least 10% relative increase from baseline) was summarized using the reverse Kaplan-Meier estimates (1 - Kaplan-Meier estimates) for the FAS.

6. Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24 [From the Baseline, Month 6, 12, 18 and Month 24]

   Cardiac iron concentration (mg Fe/g dw) was quantified using the formula (cardiac iron concentration (mg Fe/g dw) = 45 * T2* (ms) ^ (-1.22) and analyzed over time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with β-thalassemia major or Diamond-Blackfan anemia (DBA) or congenital sideroblastic anemia on chronic transfusion therapy

• Myocardial T2* value that is ≥ 5 and < 10 ms

• Left ventricular ejection fraction (LVEF) ≥ 56% as determined by Magnetic resonance imaging (MRI)

• Liver Iron Concentration (LIC) ≥ 7 mg Fe /g dw as determined by R2 MRI.

• Lifetime history of at least 50 units of red blood cell transfusions, and must be receiving at least ≥ 8 units/yr of red blood cell transfusions

• Serum ferritin ≥ 1000 ng/mL

Exclusion Criteria:

• Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias)

• Patients unable to undergo study assessments including MRI

• Patients with serum creatinine greater than Upper limit of normal ULN)range or with significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥1.0 mg/mg in a non-first void urine sample at baseline.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2C4
2	Novartis Investigative Site	Cairo		Egypt
3	Novartis Investigative Site	Athens	GR	Greece	GR-115 27
4	Novartis Investigative Site	Patra - RIO	GR	Greece	265 04
5	Novartis Investigative Site	Cagliari	CA	Italy	09121
6	Novartis Investigative Site	Genova	GE	Italy	16128
7	Novartis Investigative Site	Napoli		Italy	80138
8	Novartis Investigative Site	Taipei		Taiwan	10002
9	Novartis Investigative Site	Bangkok		Thailand	10330
10	Novartis Investigative Site	Bangkok		Thailand	10700
11	Novartis Investigative Site	Adana		Turkey	01330
12	Novartis Investigative Site	Antalya		Turkey	07070
13	Novartis Investigative Site	Istanbul		Turkey	34093
14	Novartis Investigative Site	Izmir		Turkey	35040
15	Novartis Investigative Site	London		United Kingdom	NW1 2BU

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• link to the results

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01254227
• Other Study ID Numbers: CICL670A2214; 2010-021062-29
• First Posted: Dec 6, 2010
• Last Update Posted: Jul 26, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Novartis Pharmaceuticals: Cardiac iron overload,; deferasirox,; deferoxamine
• Additional relevant MeSH terms: Iron Overload; Deferasirox; Deferoxamine

Study Results

Participant Flow

Recruitment Details	The study was conducted at 18 centers in 8 countries.
Pre-assignment Detail	A total 60 participants were enrolled in the study of which 34 completed the study.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 Milligrams per Kilogram per day (mg/kg/day) every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Period Title: Overall Study
STARTED	60
Completion of 12 Months	39
Completion of 24 Months	34
COMPLETED	34
NOT COMPLETED	26

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Overall Participants	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.8 (7.33)
Sex: Female, Male (Count of Participants)
Female	32 53.3%
Male	28 46.7%

Outcome Measures

1. Primary Outcome

Title	Change in Cardiac Iron Content From Baseline to Month 12
Description	Cardiac T2* is the most sensitive and reproducible test in detecting myocardial iron load. A cardiac T2* value of <10 ms is defined as severe cardiac iron overload. Participants who do not have baseline T2* or do not have any post-baseline T2* are excluded from the analysis.
Time Frame	From Baseline to Month 12

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Measure Participants	60
Geometric Mean (95% Confidence Interval) [ratio]	1.09

2. Secondary Outcome

Title	Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24
Description	The number of evaluable participants at each visit were used as the denominator for the calculation of proportion at each visit.
Time Frame	From the Months 6, 12, 18 and 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint. Here, "Number of participants analyzed" included all participants who were evaluable for the specified timepoints.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Measure Participants	44
Month 6	12.50 20.8%
Month12	19.23 32.1%
Month 18	33.33 55.6%
Month 24	47.22 78.7%

3. Secondary Outcome

Title	Change in Cardiac Iron Content From Baseline to Month 6,18 and 24
Description	The change in cardiac iron content was calculated as ratio of Cardiac T2* at different time points; the efficacy endpoint analyses were performed on the Full Analysis Set (FAS).
Time Frame	From Baseline to Months 6, 18 and 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint. Here, "Number of participants analyzed" included all participants who were evaluable for the specified timepoints.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Measure Participants	60
Month 6	1.02
Month 18	1.17
Month 24	1.30

4. Secondary Outcome

Title	Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24
Description	Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Time Frame	From the Months 6, 12, 18 and 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Measure Participants	60
Baseline	66.5 (5.32)
Month 6	0.1 (4.62)
Month 12	-0.2 (4.84)
Month 18	0.6 (7.04)
Month 24	0.9 (5.98)

5. Secondary Outcome

Title	Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24
Description	Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Time Frame	From the Months 6, 12, 18 and 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Measure Participants	60
Baseline	67.1 (5.55)
Month 6	-1.2 (5.35)
Month 12	-1.6 (4.40)
Month 18	-2.1 (6.10)
Month 24	-1.4 (4.25)

6. Secondary Outcome

Title	Time to Achieve From Baseline (FAS) of at Least 10% at Month 24
Description	Time from date of start of study treatment to date when first achieving T2* ≥ 10 ms (but at least 10% relative increase from baseline) was summarized using the reverse Kaplan-Meier estimates (1 - Kaplan-Meier estimates) for the FAS.
Time Frame	At 24 months

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Measure Participants	60
Median (95% Confidence Interval) [milliseconds/ms]	722.0

7. Secondary Outcome

Title	Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24
Description	Cardiac iron concentration (mg Fe/g dw) was quantified using the formula (cardiac iron concentration (mg Fe/g dw) = 45 * T2* (ms) ^ (-1.22) and analyzed over time.
Time Frame	From the Baseline, Month 6, 12, 18 and Month 24

Outcome Measure Data

Analysis Population Description

The Full Analysis Set includes all participants to whom study treatment had assigned. Participants were considered evaluable for the efficacy endpoint if they had received at least one dose of study treatment and had baseline and a post baseline assessment prior to or on the time of the assessment of the corresponding efficacy endpoint.

Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
Measure Participants	60
Baseline	4.18 (1.045)
Month 6	4.31 (1.442)
Month 12	3.93 (1.429)
Month 18	3.51 (1.348)
Month 24	3.14 (1.381)

Adverse Events

Time Frame	All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit, up to 24 months with 28 days of Follow up
Adverse Event Reporting Description	The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Arm/Group Title	All Participants
Arm/Group Description	Participants received an initial combined dose of Deferasirox (DFX) 20 mg/kg/day every day and Deferoxamine (DFO) 40 mg/kg/day (DFO: 5 days/week for at least 8 hours/day). Deferasirox was increased to 30 mg/kg/day every day at Month 1 Further dose increases upto 40 mg/kg/day every day at Month 6 visit. Participants could be switched from the Deferasirox - Deferoxamine (DFX - DFO) combination to Deferasirox monotherapy at the highest tolerable dose (30-40 mg/kg/day) at any time point after 6 months.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	1/60 (1.7%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	17/60 (28.3%)
Blood and lymphatic system disorders
Anaemia	1/60 (1.7%)
Congenital, familial and genetic disorders
Dermoid cyst	1/60 (1.7%)
Gastrointestinal disorders
Abdominal pain	2/60 (3.3%)
Irritable bowel syndrome	1/60 (1.7%)
Pancreatitis acute	1/60 (1.7%)
Reflux gastritis	1/60 (1.7%)
Vomiting	1/60 (1.7%)
General disorders
Asthenia	1/60 (1.7%)
Pyrexia	1/60 (1.7%)
Hepatobiliary disorders
Biliary colic	1/60 (1.7%)
Cholecystitis	1/60 (1.7%)
Infections and infestations
Abscess neck	1/60 (1.7%)
Bronchitis	1/60 (1.7%)
Febrile infection	1/60 (1.7%)
Infection	1/60 (1.7%)
Pharyngitis	1/60 (1.7%)
Injury, poisoning and procedural complications
Chest injury	1/60 (1.7%)
Spinal column injury	1/60 (1.7%)
Metabolism and nutrition disorders
Calcium deficiency	1/60 (1.7%)
Hyperglycaemia	1/60 (1.7%)
Hypocalcaemia	1/60 (1.7%)
Hypoglycaemia	1/60 (1.7%)
Hypophosphataemia	1/60 (1.7%)
Type 1 diabetes mellitus	1/60 (1.7%)
Musculoskeletal and connective tissue disorders
Costochondritis	1/60 (1.7%)
Myalgia	1/60 (1.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian germ cell teratoma benign	1/60 (1.7%)
Nervous system disorders
Altered state of consciousness	1/60 (1.7%)
Ischaemic stroke	1/60 (1.7%)
VIIth nerve paralysis	1/60 (1.7%)
Reproductive system and breast disorders
Fallopian tube cyst	1/60 (1.7%)
Ovarian cyst	1/60 (1.7%)
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms	1/60 (1.7%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	52/60 (86.7%)
Blood and lymphatic system disorders
Thrombocytosis	2/60 (3.3%)
Cardiac disorders
Atrioventricular block first degree	3/60 (5%)
Palpitations	2/60 (3.3%)
Sinus tachycardia	2/60 (3.3%)
Tachycardia	2/60 (3.3%)
Ear and labyrinth disorders
Conductive deafness	2/60 (3.3%)
Deafness bilateral	2/60 (3.3%)
Deafness neurosensory	3/60 (5%)
Eustachian tube dysfunction	2/60 (3.3%)
Eye disorders
Conjunctivitis	2/60 (3.3%)
Gastrointestinal disorders
Abdominal discomfort	2/60 (3.3%)
Abdominal distension	2/60 (3.3%)
Abdominal pain	8/60 (13.3%)
Abdominal pain upper	4/60 (6.7%)
Diarrhoea	8/60 (13.3%)
Dyspepsia	2/60 (3.3%)
Enteritis	3/60 (5%)
Nausea	8/60 (13.3%)
Toothache	7/60 (11.7%)
Vomiting	3/60 (5%)
General disorders
Asthenia	4/60 (6.7%)
Influenza like illness	2/60 (3.3%)
Oedema peripheral	2/60 (3.3%)
Pyrexia	14/60 (23.3%)
Infections and infestations
Acute tonsillitis	2/60 (3.3%)
Gastroenteritis	4/60 (6.7%)
Influenza	8/60 (13.3%)
Nasopharyngitis	9/60 (15%)
Pharyngitis	2/60 (3.3%)
Sinusitis	3/60 (5%)
Tonsillitis	4/60 (6.7%)
Tooth abscess	5/60 (8.3%)
Upper respiratory tract infection	10/60 (16.7%)
Injury, poisoning and procedural complications
Allergic transfusion reaction	2/60 (3.3%)
Traumatic arthritis	2/60 (3.3%)
Investigations
Blood creatinine increased	5/60 (8.3%)
Cardiac murmur	2/60 (3.3%)
Electrocardiogram QT prolonged	2/60 (3.3%)
Electrocardiogram T wave amplitude decreased	3/60 (5%)
Electrocardiogram T wave inversion	4/60 (6.7%)
Urine protein/creatinine ratio increased	6/60 (10%)
Metabolism and nutrition disorders
Hypocalcaemia	3/60 (5%)
Type 1 diabetes mellitus	2/60 (3.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/60 (13.3%)
Back pain	12/60 (20%)
Bone pain	2/60 (3.3%)
Muscle spasms	2/60 (3.3%)
Musculoskeletal chest pain	2/60 (3.3%)
Musculoskeletal pain	2/60 (3.3%)
Pain in extremity	4/60 (6.7%)
Nervous system disorders
Headache	9/60 (15%)
Paraesthesia	2/60 (3.3%)
Renal and urinary disorders
Haematuria	2/60 (3.3%)
Proteinuria	6/60 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	5/60 (8.3%)
Dysphonia	2/60 (3.3%)
Oropharyngeal pain	6/60 (10%)
Productive cough	2/60 (3.3%)
Skin and subcutaneous tissue disorders
Pruritus	2/60 (3.3%)
Rash	2/60 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.