Trial Outcomes & Findings for SCHEDULE - Scandinavian Heart Transplant Everolimus de Novo Study With Early Calcineurin Inhibitor (CNI) Avoidance (NCT NCT01266148)

Last Updated: 2015-06-10

Results Overview

Measured Glomerular Filtration Rate (mGFR) describes the flow rate of filtered fluid through the kidney. GFR is equal to the clearance rate when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys. The rate therefore measured is the quantity of the substance in the urine that originated from a calculable volume of blood. Participants' urine was used for this assessment at week 52 after heart transplant.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

115 participants

Primary outcome timeframe

Week 52

Results posted on

2015-06-10

Participant Flow

115 patients (56 in the everolimus group, 59 in the control group) were randomized and received study treatment.

Group A (control) received treatment with Cyclosporine A (CsA), Mycophenolate mofetil (MMF), and corticosteroids. Group B (everolimus), received: low-dose CsA and everolimus, reduced dose MMF, and corticosteroids. After week 7-11, CsA was discontinued in Group B, while the standard triple-drug immunosuppressive regimen was maintained in Group A.

Participant milestones

Participant milestones
Measure	Everolimus Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Overall Study STARTED	56	59
Overall Study COMPLETED	49	56
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Overall Study Adverse Event	2	0
Overall Study Ongoing rejection	1	0
Overall Study 2 2R rejections	1	0
Overall Study Death	2	3
Overall Study missing mGFR value + AE	1	0

Baseline Characteristics

SCHEDULE - Scandinavian Heart Transplant Everolimus de Novo Study With Early Calcineurin Inhibitor (CNI) Avoidance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus n=56 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=59 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.	Total n=115 Participants Total of all reporting groups
Age, Continuous	51.02 years STANDARD_DEVIATION 12.93 • n=93 Participants	51.47 years STANDARD_DEVIATION 12.36 • n=4 Participants	51.25 years STANDARD_DEVIATION 12.59 • n=27 Participants
Sex: Female, Male Female	17 Participants n=93 Participants	14 Participants n=4 Participants	31 Participants n=27 Participants
Sex: Female, Male Male	39 Participants n=93 Participants	45 Participants n=4 Participants	84 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 52

Population: The intent to treat population includes the full analysis set patients with available data and without any major protocol deviations or criteria causing exclusion and for which data was available for analysis. Patients were analyzed according to the treatment to which they were randomized.

Outcome measures

Outcome measures
Measure	Everolimus n=51 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=56 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Measured Glomerular Filtration Rate (mGFR), 12 Months After Heart Transplantation	79.8 mGFR ml/min Standard Deviation 17.7	61.5 mGFR ml/min Standard Deviation 19.6

SECONDARY outcome

Timeframe: Baseline and week 52

The progression of chronic allograft vasculopathy (CAV) was assessed by intravascular ultrasound (IVUS) examinations and measured Maximal Intimal Thickness (MIT)(in mm). A major coronary epicardial artery (preferentially the left-anterior descending coronary artery) was imaged, and the MIT parameters were recorded at baseline and at week 52.

Outcome measures

Outcome measures
Measure	Everolimus n=46 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=48 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Progression of Chronic Allograft Vasculopathy (CAV) Based on Maximal Intimal Thickness (MIT) From Baseline to Week 52 Week 52	0.55 mm Standard Deviation 0.24	0.65 mm Standard Deviation 0.25
Progression of Chronic Allograft Vasculopathy (CAV) Based on Maximal Intimal Thickness (MIT) From Baseline to Week 52 Baseline (Week 7)	0.52 mm Standard Deviation 0.22	0.56 mm Standard Deviation 0.24

SECONDARY outcome

Timeframe: Baseline and week 52

the progression of chronic allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) examinations, measured the incidence of CAV (in percent of patients) at baseline and at week 52. Incidence of CAV represents percent of patients having a MIT (maximal intima thickness) \> 0.5 mm.

Outcome measures

Outcome measures
Measure	Everolimus n=46 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=48 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Progression of Chronic Allograft Vasculopathy (CAV) Based on Incidence of Chronic Allograft Vasculopathy (CAV) From Baseline to Week 52 No CAV at baseline (week 7)	43.5 Percentage of patients	47.9 Percentage of patients
Progression of Chronic Allograft Vasculopathy (CAV) Based on Incidence of Chronic Allograft Vasculopathy (CAV) From Baseline to Week 52 CAV at baseline (week 7)	56.5 Percentage of patients	52.1 Percentage of patients
Progression of Chronic Allograft Vasculopathy (CAV) Based on Incidence of Chronic Allograft Vasculopathy (CAV) From Baseline to Week 52 No CAV at week 52	50 Percentage of patients	35.4 Percentage of patients
Progression of Chronic Allograft Vasculopathy (CAV) Based on Incidence of Chronic Allograft Vasculopathy (CAV) From Baseline to Week 52 CAV at week 52	50 Percentage of patients	64.6 Percentage of patients

SECONDARY outcome

Timeframe: Day 1, weeks 7 to 11(baseline) and of week 52

Change in calculated glomerular filtration rate from pre-transplantation to week 52 was calculated according to the Modification of Diet in Renal Disease (MDRD) method. Measurements were taken prior to transplant (day 1), between weeks 7 to 11 and end week 52.

Outcome measures

Outcome measures
Measure	Everolimus n=46 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=53 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Change in Calculated Glomerular Filtration Rate From Pre-transplantation to Week 52 Day 1 (n= 43, 47)	-13.0 mGFR mL/min Standard Deviation 28.2	-12.6 mGFR mL/min Standard Deviation 32.6
Change in Calculated Glomerular Filtration Rate From Pre-transplantation to Week 52 Weeks 7 to 11 (n= 46, 49)	7.4 mGFR mL/min Standard Deviation 32.6	-6.8 mGFR mL/min Standard Deviation 26.2
Change in Calculated Glomerular Filtration Rate From Pre-transplantation to Week 52 Week 52 (n= 42, 53)	27.8 mGFR mL/min Standard Deviation 49.9	-8.0 mGFR mL/min Standard Deviation 28.3

SECONDARY outcome

Timeframe: Day 1, weeks 7 to 11 and of week 52

Calculated Glomerular Filtration Rate from pre-transplantation to week 52 was calculated according to the Modification of Diet in Renal Disease (MDRD) method. Measurements were taken prior to transplant (day 1), between weeks 7 to 11 and end of week 52.

Outcome measures

Outcome measures
Measure	Everolimus n=50 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=55 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Calculated Glomerular Filtration Rate From Pre-Transplantation to Week 52 Day 1 (n= 46, 48)	65.4 mGFR mL/min Standard Deviation 33.8	66.1 mGFR mL/min Standard Deviation 28.7
Calculated Glomerular Filtration Rate From Pre-Transplantation to Week 52 Weeks 7 to 11 (n=50, 51)	84.9 mGFR mL/min Standard Deviation 40.5	69.6 mGFR mL/min Standard Deviation 19.9
Calculated Glomerular Filtration Rate From Pre-Transplantation to Week 52 Week 52 (n= 45, 55)	104.5 mGFR mL/min Standard Deviation 54.0	69.3 mGFR mL/min Standard Deviation 20.4

SECONDARY outcome

Timeframe: 52 weeks

Number of all rejections were recorded through the duration of the study with the intent to identify rejections leading to hemodynamic compromise.

Outcome measures

Outcome measures
Measure	Everolimus n=52 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=56 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Number of Rejections Leading to Hemodynamic Compromise Total rejection	185 rejections	128 rejections
Number of Rejections Leading to Hemodynamic Compromise Treated rejection	43 rejections	17 rejections
Number of Rejections Leading to Hemodynamic Compromise Rejections with hemodynamic compromise	0 rejections	0 rejections

SECONDARY outcome

Timeframe: 52 weeks

Treatment failure was defined as the number of participants who died or lost their graft at any timepoint througout the duration of the study.

Outcome measures

Outcome measures
Measure	Everolimus n=56 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=59 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Occurrence of Treatment Failures up to 12 Months After Transplant Treatment failure (death)	2 participants	3 participants
Occurrence of Treatment Failures up to 12 Months After Transplant Graff loss	0 participants	0 participants
Occurrence of Treatment Failures up to 12 Months After Transplant Total treatment failures (graft loss + death	2 participants	3 participants

SECONDARY outcome

Timeframe: 52 weeks

Population: The safety sert include all randomized participants who received at least one dose of study medication and were able to provide urine samples at week 52.

Proteinuria is measured as the ratio of albumin/creatinine mg/mmol. Measurements were taken from participants urine samples.

Outcome measures

Outcome measures
Measure	Everolimus n=52 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=56 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Average Level of Protenuria at Week 52	7.2 mg/mmol Standard Deviation 12.8	1.2 mg/mmol Standard Deviation 1.4

SECONDARY outcome

Timeframe: 52 weeks

Population: The safety sert include all randomized participants who received at least one dose of study medication and had blood samples taken at week 52.

Total Cholesterol, LDL-Chol, HDL-Chol and TG at week 52. Measurements were taken via participants blood samples.

Outcome measures

Outcome measures
Measure	Everolimus n=53 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=56 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Lipid Profile at 12 Months HDL-C	1.6 mmol/L Standard Deviation 0.5	1.6 mmol/L Standard Deviation 0.5
Lipid Profile at 12 Months Total cholesterol	5.3 mmol/L Standard Deviation 1.1	5.1 mmol/L Standard Deviation 1.0
Lipid Profile at 12 Months LDL-C	2.9 mmol/L Standard Deviation 1.0	2.8 mmol/L Standard Deviation 0.8

SECONDARY outcome

Timeframe: Pre transplant and 52 weeks

Change in Quality of Life was assessed via the SF-36 (Minnesota Living with Heart Failure questionnaire (\[MLHF)\]) before transplant surgery and at week 52 of treatment. The SF-36 is a validated, self-administered questionnaire. The questionnaire, which includes 36 questions measures 8 dimensions of health: physical function, role-physical, bodily pain, general health, vitality, social function, role-emotional, and mental health. Scores can be summarized in 2 summary components assessing physical and mental health. Items in each dimension are coded, aggregated, summed, and transformed into a scale ranging from 0 (worse health) to 100 (best health).

Outcome measures

Outcome measures
Measure	Everolimus n=41 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=45 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Change in Quality of Life Assessed by SF-36 (Minnesota Living With Heart Failure Questionnaire ([MLHF)]) From Pre-transplant to Week 52 of Treatment Physical Health pre- transplant	30.8 Units on a scale Standard Deviation 11.1	32.9 Units on a scale Standard Deviation 8.0
Change in Quality of Life Assessed by SF-36 (Minnesota Living With Heart Failure Questionnaire ([MLHF)]) From Pre-transplant to Week 52 of Treatment Physical Health at week 52	48.8 Units on a scale Standard Deviation 9.6	48.8 Units on a scale Standard Deviation 8.3
Change in Quality of Life Assessed by SF-36 (Minnesota Living With Heart Failure Questionnaire ([MLHF)]) From Pre-transplant to Week 52 of Treatment Mental Health pre- transplant	46.2 Units on a scale Standard Deviation 11.8	38.7 Units on a scale Standard Deviation 12.4
Change in Quality of Life Assessed by SF-36 (Minnesota Living With Heart Failure Questionnaire ([MLHF)]) From Pre-transplant to Week 52 of Treatment Mental Health at week 52	51.5 Units on a scale Standard Deviation 12.2	53.9 Units on a scale Standard Deviation 7.2

SECONDARY outcome

Timeframe: Pre transplant and 52 weeks

Change in Quality of Life was assessed via the EQ-5D questionnaire which consists of: EQ-5D-5L descriptive system and EQ Visual Analogue scale (EQ VAS). The EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). The patient indicates his/her health state by checking the most appropriate statement. This decision results in a 1-digit number expressing the level selected for that dimension. The digits for 5 dimensions are combined in a 5-digit number describing the respondent's health state. The possible score is 1 to 5 where a lower number indicates improvement. The EQ VAS records the patient's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. The score is 0 to 100 where a higher score represents improvement.

Outcome measures

Outcome measures
Measure	Everolimus n=45 Participants Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.	Control n=49 Participants Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study.
Change in Quality of Life - Euro Quality of Life 5D (EQ-5D) EQ-5D-5L pre- transplant (n=45,49)	0.5750 Units on a scale Standard Deviation 0.3387	0.5069 Units on a scale Standard Deviation 0.3209
Change in Quality of Life - Euro Quality of Life 5D (EQ-5D) EQ-5D-5L at week 52 (n=41,44)	0.8329 Units on a scale Standard Deviation 0.2638	0.8367 Units on a scale Standard Deviation 0.2234
Change in Quality of Life - Euro Quality of Life 5D (EQ-5D) EQ VAS pre- transplant (n=41,48)	46.0 Units on a scale Standard Deviation 24.3	38.9 Units on a scale Standard Deviation 20.8
Change in Quality of Life - Euro Quality of Life 5D (EQ-5D) EQ VAS at week 52 (n=41,42)	80.0 Units on a scale Standard Deviation 15.0	79.4 Units on a scale Standard Deviation 11.5

Adverse Events

Controls

Serious events: 27 serious events

Other events: 53 other events

Deaths: 0 deaths

Everolimus

Serious events: 27 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Controls n=59 participants at risk Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study	Everolimus n=56 participants at risk Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Blood and lymphatic system disorders Neutropenia	1.7% 1/59	0.00% 0/56
Cardiac disorders Arrhythmia	1.7% 1/59	1.8% 1/56
Cardiac disorders Atrial fibrillation	0.00% 0/59	1.8% 1/56
Cardiac disorders Atrioventricular block complete	1.7% 1/59	0.00% 0/56
Cardiac disorders Cardiac arrest	1.7% 1/59	0.00% 0/56
Cardiac disorders Cardiac disorder	1.7% 1/59	5.4% 3/56
Cardiac disorders Palpitations	1.7% 1/59	0.00% 0/56
Gastrointestinal disorders Abdominal hernia	0.00% 0/59	1.8% 1/56
Gastrointestinal disorders Constipation	1.7% 1/59	0.00% 0/56
Gastrointestinal disorders Diarrhoea	5.1% 3/59	0.00% 0/56
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/59	1.8% 1/56
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/59	1.8% 1/56
Gastrointestinal disorders Large intestine perforation	0.00% 0/59	1.8% 1/56
Gastrointestinal disorders Megacolon	0.00% 0/59	1.8% 1/56
Gastrointestinal disorders Melaena	0.00% 0/59	1.8% 1/56
General disorders Device malfunction	1.7% 1/59	0.00% 0/56
General disorders Impaired healing	0.00% 0/59	1.8% 1/56
General disorders Multi-organ failure	3.4% 2/59	1.8% 1/56
General disorders Pyrexia	5.1% 3/59	0.00% 0/56
Infections and infestations Bronchitis	1.7% 1/59	1.8% 1/56
Infections and infestations Cytomegalovirus infection	5.1% 3/59	0.00% 0/56
Infections and infestations Gastroenteritis	1.7% 1/59	0.00% 0/56
Infections and infestations Gastroenteritis norovirus	0.00% 0/59	1.8% 1/56
Infections and infestations Haemophilus infection	0.00% 0/59	1.8% 1/56
Infections and infestations Infection	5.1% 3/59	1.8% 1/56
Infections and infestations Nasopharyngitis	1.7% 1/59	0.00% 0/56
Infections and infestations Osteomyelitis	1.7% 1/59	0.00% 0/56
Infections and infestations Pneumonia	1.7% 1/59	8.9% 5/56
Infections and infestations Sepsis	1.7% 1/59	0.00% 0/56
Infections and infestations Urinary tract infection	1.7% 1/59	1.8% 1/56
Infections and infestations Wound infection	0.00% 0/59	1.8% 1/56
Injury, poisoning and procedural complications Graft complication	0.00% 0/59	1.8% 1/56
Injury, poisoning and procedural complications Hip fracture	0.00% 0/59	1.8% 1/56
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/59	1.8% 1/56
Injury, poisoning and procedural complications Rib fracture	1.7% 1/59	0.00% 0/56
Metabolism and nutrition disorders Dehydration	1.7% 1/59	0.00% 0/56
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/59	1.8% 1/56
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/59	1.8% 1/56
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/59	1.8% 1/56
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.00% 0/59	1.8% 1/56
Nervous system disorders Brain stem syndrome	1.7% 1/59	0.00% 0/56
Nervous system disorders Cerebral haemorrhage	1.7% 1/59	0.00% 0/56
Nervous system disorders Cerebrovascular accident	1.7% 1/59	0.00% 0/56
Nervous system disorders Epilepsy	3.4% 2/59	0.00% 0/56
Nervous system disorders Headache	0.00% 0/59	1.8% 1/56
Nervous system disorders Presyncope	0.00% 0/59	1.8% 1/56
Nervous system disorders Syncope	1.7% 1/59	0.00% 0/56
Psychiatric disorders Confusional state	1.7% 1/59	0.00% 0/56
Psychiatric disorders Depression	0.00% 0/59	3.6% 2/56
Psychiatric disorders Psychotic disorder	1.7% 1/59	0.00% 0/56
Renal and urinary disorders Renal failure	0.00% 0/59	1.8% 1/56
Renal and urinary disorders Renal failure acute	1.7% 1/59	0.00% 0/56
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/59	1.8% 1/56
Respiratory, thoracic and mediastinal disorders Chylothorax	1.7% 1/59	0.00% 0/56
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 1/59	3.6% 2/56
Respiratory, thoracic and mediastinal disorders Pleural haemorrhage	0.00% 0/59	1.8% 1/56
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.7% 1/59	1.8% 1/56
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.4% 2/59	0.00% 0/56
Surgical and medical procedures Pericardial drainage	0.00% 0/59	1.8% 1/56
Surgical and medical procedures Suture removal	1.7% 1/59	0.00% 0/56
Vascular disorders Air embolism	1.7% 1/59	0.00% 0/56
Vascular disorders Femoral artery occlusion	0.00% 0/59	1.8% 1/56

Other adverse events

Other adverse events
Measure	Controls n=59 participants at risk Participants received an immunosuppressive regimen consisting of CsA, MMF and CS throughout the study	Everolimus n=56 participants at risk Participants started immunosuppressive regimen consisting of low dose CsA, everolimus, MMF and CS. After week 11, the participants regimen consisted of everolimus, MMF and CS.
Blood and lymphatic system disorders Anaemia	8.5% 5/59	14.3% 8/56
Blood and lymphatic system disorders Leukopenia	22.0% 13/59	19.6% 11/56
Blood and lymphatic system disorders Thrombocytopenia	5.1% 3/59	3.6% 2/56
Cardiac disorders Arrhythmia	15.3% 9/59	10.7% 6/56
Cardiac disorders Cardiac disorder	1.7% 1/59	12.5% 7/56
Cardiac disorders Pericardial effusion	3.4% 2/59	7.1% 4/56
Gastrointestinal disorders Diarrhoea	3.4% 2/59	17.9% 10/56
General disorders Oedema	1.7% 1/59	7.1% 4/56
General disorders Oedema peripheral	16.9% 10/59	21.4% 12/56
General disorders Pyrexia	1.7% 1/59	5.4% 3/56
Infections and infestations Candidiasis	0.00% 0/59	5.4% 3/56
Infections and infestations Cytomegalovirus infection	25.4% 15/59	5.4% 3/56
Infections and infestations Herpes simplex	5.1% 3/59	1.8% 1/56
Infections and infestations Infection	15.3% 9/59	17.9% 10/56
Infections and infestations Nasopharyngitis	11.9% 7/59	16.1% 9/56
Infections and infestations Pneumonia	1.7% 1/59	7.1% 4/56
Infections and infestations Urinary tract infection	1.7% 1/59	8.9% 5/56
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/59	7.1% 4/56
Metabolism and nutrition disorders Gout	5.1% 3/59	3.6% 2/56
Metabolism and nutrition disorders Hypercholesterolaemia	3.4% 2/59	5.4% 3/56
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.8% 4/59	8.9% 5/56
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/59	5.4% 3/56
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 3/59	5.4% 3/56
Nervous system disorders Headache	1.7% 1/59	5.4% 3/56
Nervous system disorders Tremor	13.6% 8/59	5.4% 3/56
Renal and urinary disorders Nephropathy toxic	5.1% 3/59	3.6% 2/56
Renal and urinary disorders Renal failure	5.1% 3/59	3.6% 2/56
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.9% 7/59	19.6% 11/56
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.1% 3/59	0.00% 0/56
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.7% 1/59	5.4% 3/56
Skin and subcutaneous tissue disorders Acne	1.7% 1/59	10.7% 6/56
Skin and subcutaneous tissue disorders Hirsutism	6.8% 4/59	0.00% 0/56
Skin and subcutaneous tissue disorders Rash	8.5% 5/59	8.9% 5/56
Vascular disorders Hypertension	33.9% 20/59	17.9% 10/56

Additional Information

Study director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER