Trial Outcomes & Findings for Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload (NCT NCT01254227)

Last Updated: 2021-07-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

From Baseline to Month 12

Results posted on

2021-07-26

Participant Flow

The study was conducted at 18 centers in 8 countries.

A total 60 participants were enrolled in the study of which 34 completed the study.

Participant milestones

Participant milestones
Measure	All Participants 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.
Overall Study STARTED	60
Overall Study Completion of 12 Months	39
Overall Study Completion of 24 Months	34
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	26

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants 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.
Overall Study Withdrawal by Subject	6
Overall Study Lost to Follow-up	6
Overall Study Adverse Event	5
Overall Study Abnormal test procedure result	5
Overall Study Administrative problems	2
Overall Study Death	1
Overall Study Protocol deviation	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=60 Participants 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.
Age, Continuous	22.8 years STANDARD_DEVIATION 7.33 • n=99 Participants
Sex: Female, Male Female	32 Participants n=99 Participants
Sex: Female, Male Male	28 Participants n=99 Participants

PRIMARY outcome

Timeframe: From Baseline to Month 12

Population: 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.

Outcome measures

Outcome measures
Measure	All Participants n=60 Participants 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.
Change in Cardiac Iron Content From Baseline to Month 12	1.09 ratio Interval 1.04 to 1.15

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=44 Participants 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.
Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24 Month 6	12.50 percentage of participants Interval 5.86 to 24.7
Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24 Month12	19.23 percentage of participants Interval 10.8 to 31.9
Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24 Month 18	33.33 percentage of participants Interval 19.75 to 50.39
Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24 Month 24	47.22 percentage of participants Interval 31.99 to 62.99

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	All Participants n=60 Participants 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.
Change in Cardiac Iron Content From Baseline to Month 6,18 and 24 Month 6	1.02 ratio Interval 0.98 to 1.07
Change in Cardiac Iron Content From Baseline to Month 6,18 and 24 Month 18	1.17 ratio Interval 1.08 to 1.28
Change in Cardiac Iron Content From Baseline to Month 6,18 and 24 Month 24	1.30 ratio Interval 1.17 to 1.44

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=60 Participants 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.
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24 Baseline	66.5 Percent Ejection Fraction Standard Deviation 5.32
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24 Month 6	0.1 Percent Ejection Fraction Standard Deviation 4.62
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24 Month 12	-0.2 Percent Ejection Fraction Standard Deviation 4.84
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24 Month 18	0.6 Percent Ejection Fraction Standard Deviation 7.04
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24 Month 24	0.9 Percent Ejection Fraction Standard Deviation 5.98

SECONDARY outcome

Timeframe: From the Months 6, 12, 18 and 24

Outcome measures

Outcome measures
Measure	All Participants n=60 Participants 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.
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24 Baseline	67.1 Percent Ejection Fraction Standard Deviation 5.55
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24 Month 6	-1.2 Percent Ejection Fraction Standard Deviation 5.35
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24 Month 12	-1.6 Percent Ejection Fraction Standard Deviation 4.40
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24 Month 18	-2.1 Percent Ejection Fraction Standard Deviation 6.10
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24 Month 24	-1.4 Percent Ejection Fraction Standard Deviation 4.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=60 Participants 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.
Time to Achieve From Baseline (FAS) of at Least 10% at Month 24	722.0 milliseconds/ms Interval 520.0 to NA: It was not estimable.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=60 Participants 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.
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24 Baseline	4.18 mg Fe/g dw Standard Deviation 1.045
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24 Month 6	4.31 mg Fe/g dw Standard Deviation 1.442
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24 Month 12	3.93 mg Fe/g dw Standard Deviation 1.429
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24 Month 18	3.51 mg Fe/g dw Standard Deviation 1.348
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24 Month 24	3.14 mg Fe/g dw Standard Deviation 1.381

Adverse Events

All Participants

Serious events: 17 serious events

Other events: 52 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=60 participants at risk 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.
Blood and lymphatic system disorders Anaemia	1.7% 1/60 • 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 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.
Congenital, familial and genetic disorders Dermoid cyst	1.7% 1/60 • 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 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.
Gastrointestinal disorders Abdominal pain	3.3% 2/60 • 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 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.
Gastrointestinal disorders Irritable bowel syndrome	1.7% 1/60 • 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 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.
Gastrointestinal disorders Pancreatitis acute	1.7% 1/60 • 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 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.
Gastrointestinal disorders Reflux gastritis	1.7% 1/60 • 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 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.
Gastrointestinal disorders Vomiting	1.7% 1/60 • 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 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.
General disorders Asthenia	1.7% 1/60 • 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 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.
General disorders Pyrexia	1.7% 1/60 • 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 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.
Hepatobiliary disorders Biliary colic	1.7% 1/60 • 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 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.
Hepatobiliary disorders Cholecystitis	1.7% 1/60 • 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 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.
Infections and infestations Abscess neck	1.7% 1/60 • 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 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.
Infections and infestations Bronchitis	1.7% 1/60 • 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 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.
Infections and infestations Febrile infection	1.7% 1/60 • 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 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.
Infections and infestations Infection	1.7% 1/60 • 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 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.
Infections and infestations Pharyngitis	1.7% 1/60 • 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 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.
Injury, poisoning and procedural complications Chest injury	1.7% 1/60 • 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 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.
Injury, poisoning and procedural complications Spinal column injury	1.7% 1/60 • 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 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.
Metabolism and nutrition disorders Calcium deficiency	1.7% 1/60 • 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 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.
Metabolism and nutrition disorders Hyperglycaemia	1.7% 1/60 • 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 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.
Metabolism and nutrition disorders Hypocalcaemia	1.7% 1/60 • 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 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.
Metabolism and nutrition disorders Hypoglycaemia	1.7% 1/60 • 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 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.
Metabolism and nutrition disorders Hypophosphataemia	1.7% 1/60 • 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 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.
Metabolism and nutrition disorders Type 1 diabetes mellitus	1.7% 1/60 • 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 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.
Musculoskeletal and connective tissue disorders Costochondritis	1.7% 1/60 • 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 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.
Musculoskeletal and connective tissue disorders Myalgia	1.7% 1/60 • 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 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian germ cell teratoma benign	1.7% 1/60 • 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 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.
Nervous system disorders Altered state of consciousness	1.7% 1/60 • 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 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.
Nervous system disorders Ischaemic stroke	1.7% 1/60 • 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 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.
Nervous system disorders VIIth nerve paralysis	1.7% 1/60 • 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 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.
Reproductive system and breast disorders Fallopian tube cyst	1.7% 1/60 • 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 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.
Reproductive system and breast disorders Ovarian cyst	1.7% 1/60 • 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 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.
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	1.7% 1/60 • 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 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.

Other adverse events

Other adverse events
Measure	All Participants n=60 participants at risk 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.
Blood and lymphatic system disorders Thrombocytosis	3.3% 2/60 • 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 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.
Cardiac disorders Atrioventricular block first degree	5.0% 3/60 • 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 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.
Cardiac disorders Palpitations	3.3% 2/60 • 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 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.
Cardiac disorders Sinus tachycardia	3.3% 2/60 • 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 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.
Cardiac disorders Tachycardia	3.3% 2/60 • 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 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.
Ear and labyrinth disorders Conductive deafness	3.3% 2/60 • 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 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.
Ear and labyrinth disorders Deafness bilateral	3.3% 2/60 • 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 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.
Ear and labyrinth disorders Deafness neurosensory	5.0% 3/60 • 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 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.
Ear and labyrinth disorders Eustachian tube dysfunction	3.3% 2/60 • 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 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.
Eye disorders Conjunctivitis	3.3% 2/60 • 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 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.
Gastrointestinal disorders Abdominal discomfort	3.3% 2/60 • 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 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.
Gastrointestinal disorders Abdominal distension	3.3% 2/60 • 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 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.
Gastrointestinal disorders Abdominal pain	13.3% 8/60 • 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 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.
Gastrointestinal disorders Abdominal pain upper	6.7% 4/60 • 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 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.
Gastrointestinal disorders Diarrhoea	13.3% 8/60 • 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 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.
Gastrointestinal disorders Dyspepsia	3.3% 2/60 • 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 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.
Gastrointestinal disorders Enteritis	5.0% 3/60 • 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 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.
Gastrointestinal disorders Nausea	13.3% 8/60 • 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 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.
Gastrointestinal disorders Toothache	11.7% 7/60 • 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 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.
Gastrointestinal disorders Vomiting	5.0% 3/60 • 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 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.
General disorders Asthenia	6.7% 4/60 • 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 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.
General disorders Influenza like illness	3.3% 2/60 • 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 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.
General disorders Oedema peripheral	3.3% 2/60 • 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 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.
General disorders Pyrexia	23.3% 14/60 • 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 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.
Infections and infestations Acute tonsillitis	3.3% 2/60 • 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 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.
Infections and infestations Gastroenteritis	6.7% 4/60 • 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 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.
Infections and infestations Influenza	13.3% 8/60 • 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 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.
Infections and infestations Nasopharyngitis	15.0% 9/60 • 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 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.
Infections and infestations Pharyngitis	3.3% 2/60 • 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 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.
Infections and infestations Sinusitis	5.0% 3/60 • 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 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.
Infections and infestations Tonsillitis	6.7% 4/60 • 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 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.
Infections and infestations Tooth abscess	8.3% 5/60 • 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 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.
Infections and infestations Upper respiratory tract infection	16.7% 10/60 • 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 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.
Injury, poisoning and procedural complications Allergic transfusion reaction	3.3% 2/60 • 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 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.
Injury, poisoning and procedural complications Traumatic arthritis	3.3% 2/60 • 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 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.
Investigations Blood creatinine increased	8.3% 5/60 • 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 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.
Investigations Cardiac murmur	3.3% 2/60 • 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 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.
Investigations Electrocardiogram QT prolonged	3.3% 2/60 • 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 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.
Investigations Electrocardiogram T wave amplitude decreased	5.0% 3/60 • 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 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.
Investigations Electrocardiogram T wave inversion	6.7% 4/60 • 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 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.
Investigations Urine protein/creatinine ratio increased	10.0% 6/60 • 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 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.
Metabolism and nutrition disorders Hypocalcaemia	5.0% 3/60 • 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 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.
Metabolism and nutrition disorders Type 1 diabetes mellitus	3.3% 2/60 • 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 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.
Musculoskeletal and connective tissue disorders Arthralgia	13.3% 8/60 • 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 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.
Musculoskeletal and connective tissue disorders Back pain	20.0% 12/60 • 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 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.
Musculoskeletal and connective tissue disorders Bone pain	3.3% 2/60 • 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 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.
Musculoskeletal and connective tissue disorders Muscle spasms	3.3% 2/60 • 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 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.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.3% 2/60 • 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 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.3% 2/60 • 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 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.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 4/60 • 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 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.
Nervous system disorders Headache	15.0% 9/60 • 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 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.
Nervous system disorders Paraesthesia	3.3% 2/60 • 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 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.
Renal and urinary disorders Haematuria	3.3% 2/60 • 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 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.
Renal and urinary disorders Proteinuria	10.0% 6/60 • 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 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.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 5/60 • 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 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.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.3% 2/60 • 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 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 6/60 • 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 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.
Respiratory, thoracic and mediastinal disorders Productive cough	3.3% 2/60 • 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 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.
Skin and subcutaneous tissue disorders Pruritus	3.3% 2/60 • 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 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.
Skin and subcutaneous tissue disorders Rash	3.3% 2/60 • 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 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.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place