Trial Outcomes & Findings for A Study Investigating the Renal Tolerability, Efficacy, and Safety of a CNI-free Versus a Standard Regimen in de Novo Heart Transplant (HTx) Recipients (NCT NCT00862979)

Last Updated: 2018-08-07

Results Overview

Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18 cGFR (in mL/min/1.73 m2) = 186.3\*(C-1.154)\*(A-0.203)\*G\*R where C = the serum concentration of creatinine (mg/dL), A = age (years), G = 0.742 when gender is female, otherwise G = 1, R = 1.21 when race is black, otherwise R = 1.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

162 participants

Primary outcome timeframe

Month 18

Results posted on

2018-08-07

Participant Flow

232 patients were screened, of these , 193 patients were included in safety set which included 31 non-randomized and 162 randomized. Of these, 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable and included in the Full Analysis Set FAS.

Participant milestones

Participant milestones
Measure	CNI-regimen CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Overall Study STARTED	84	78
Overall Study Full Analysis Set (FAS)	74	71
Overall Study COMPLETED	76	71
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	CNI-regimen CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Overall Study Adverse Event	6	3
Overall Study Protocol Violation	0	1
Overall Study Patient withdrew consent	2	1
Overall Study Administrative problems	0	1
Overall Study Death	0	1

Baseline Characteristics

Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CNI-regimen n=74 Participants CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=71 Participants CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids	Total n=145 Participants Total of all reporting groups
Age, Continuous	52.7 years STANDARD_DEVIATION 9.7 • n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	50.3 years STANDARD_DEVIATION 9.8 • n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	51.5 years STANDARD_DEVIATION 9.8 • n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Sex: Female, Male Female	9 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	12 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	21 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Sex: Female, Male Male	65 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	59 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	124 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Race (NIH/OMB) Asian	0 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Race (NIH/OMB) White	74 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	71 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	145 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Race (NIH/OMB) More than one race	0 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=107 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable	0 Participants n=206 Participants • Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable

PRIMARY outcome

Timeframe: Month 18

Population: Full Analysis Set-Last observation carried forward (FAS-LOCF)- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable but for this analysis only participants that had values at Month 18 were analyzed

Outcome measures

Outcome measures
Measure	CNI-regimen n=69 Participants CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=65 Participants CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 18	54.2 mL/min Standard Deviation 17.9	66.9 mL/min Standard Deviation 23.0

SECONDARY outcome

Timeframe: Month 6 to Month 9; Month 9 to Month 18

Population: Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable

Treatment failure was defined as composite endpoint of biopsy proven acute rejection of ISHLT 1990 grade ≥ 3A resp. ISHLT 2004 grade ≥ 2R, acute rejection episodes associated with hemodynamic compromise, graft loss / re-transplant, death, loss to follow up (at least one condition must be present). If participant had an occurrence in each period it was counted for each period.

Outcome measures

Outcome measures
Measure	CNI-regimen n=74 Participants CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=74 Participants CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 18 Month 6 to Month 9 Treatment failure - all reasons	1 Occurences	4 Occurences
Occurrence of Treatment Failures From Month 6 to 9 and Month 9 to 18 Month 9 to Month 18 Treatment failure-all reasons	3 Occurences	15 Occurences

SECONDARY outcome

Timeframe: Month 6 to Month 18

Population: Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable

Major cardiac events (MACE) was defined as one of the following: any death, myocardial infarction, coronary artery bypass grafting

Outcome measures

Outcome measures
Measure	CNI-regimen n=74 Participants CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=71 Participants CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Occurrence of Major Cardiac Events (MACE) From Month 6 to 18 Myocardial infarction	1 Occurences	0 Occurences
Occurrence of Major Cardiac Events (MACE) From Month 6 to 18 Death	0 Occurences	1 Occurences

SECONDARY outcome

Timeframe: Month 12 and 18

Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 12 and 18. For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl)

Outcome measures

Outcome measures
Measure	CNI-regimen n=74 Participants CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=71 Participants CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18 Month 12	54.2 mL/min Standard Deviation 19.7	69.8 mL/min Standard Deviation 23.4
Calculated Glomerular Filtration Rate (cGFR) According to Cockcroft-Gault at Month 12 and 18 Month 18	54.2 mL/min Standard Deviation 17.9	66.9 mL/min Standard Deviation 23.00

SECONDARY outcome

Timeframe: Month 6, 8, 9, 10 12 and 18

Population: Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable

Serum Creatinine is an indicator of renal function measured in the blood

Outcome measures

Outcome measures
Measure	CNI-regimen n=74 Participants CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=71 Participants CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Serum Creatinine at Month 6, 8, 9, 10 12 and 18 Month 12	1.53 μmol/L Standard Deviation 0.52	1.22 μmol/L Standard Deviation 0.33
Serum Creatinine at Month 6, 8, 9, 10 12 and 18 Month 6	1.53 μmol/L Standard Deviation 0.49	1.49 μmol/L Standard Deviation 0.51
Serum Creatinine at Month 6, 8, 9, 10 12 and 18 Month 8	1.44 μmol/L Standard Deviation 0.41	1.27 μmol/L Standard Deviation 0.35
Serum Creatinine at Month 6, 8, 9, 10 12 and 18 Month 9	1.58 μmol/L Standard Deviation 0.75	1.24 μmol/L Standard Deviation 0.32
Serum Creatinine at Month 6, 8, 9, 10 12 and 18 Month 10	1.53 μmol/L Standard Deviation 0.53	1.20 μmol/L Standard Deviation 0.30
Serum Creatinine at Month 6, 8, 9, 10 12 and 18 Month 18	1.50 μmol/L Standard Deviation 0.50	1.27 μmol/L Standard Deviation 0.44

SECONDARY outcome

Timeframe: Between Month 6 and Month 18

Population: Full Analysis Set FAS- 145 patients were treated with study medication and had at least 1 post-baseline assessment of the primary outcome variable

Reciprocal Creatinine Slope is an indication of renal function over time with a higher slope value indicating an improvement in renal function.

Outcome measures

Outcome measures
Measure	CNI-regimen n=74 Participants CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=71 Participants CNI-free regimen: everolimus (EVR) with MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and corticosteroids
Reciprocal Creatinine Slope Between Month 6 and Month 18	0.045 1/(μmol/L)/(hour) Standard Deviation 0.364	0.403 1/(μmol/L)/(hour) Standard Deviation 1.863

Adverse Events

CNI-regimen

Serious events: 40 serious events

Other events: 74 other events

Deaths: 0 deaths

CNI-free-regimen

Serious events: 29 serious events

Other events: 65 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 8627788300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	CNI-regimen n=84 participants at risk CNI-regimen: cyclosporine A (CyA) or tacrolimus (TAC) with everolimus (EVR) with corticosteroids	CNI-free-regimen n=78 participants at risk CNI-free regimen: MPA (either MMF or enteric coated mycophenolate sodium (EC-MPS)) and everolimus and corticosteroids; On month 6 to 9 only: Cyclosporin A or tacrolimus
Blood and lymphatic system disorders ANAEMIA	7.1% 6/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	9.0% 7/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Blood and lymphatic system disorders LEUKOPENIA	11.9% 10/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	12.8% 10/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Cardiac disorders SINUS TACHYCARDIA	3.6% 3/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Cardiac disorders TACHYCARDIA	9.5% 8/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	9.0% 7/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Endocrine disorders HYPERTHYROIDISM	7.1% 6/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	5.1% 4/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Gastrointestinal disorders APHTHOUS ULCER	4.8% 4/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Gastrointestinal disorders DIARRHOEA	13.1% 11/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Gastrointestinal disorders NAUSEA	11.9% 10/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	7.7% 6/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Gastrointestinal disorders VOMITING	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	2.6% 2/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
General disorders FATIGUE	3.6% 3/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	5.1% 4/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
General disorders OEDEMA	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	2.6% 2/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
General disorders OEDEMA PERIPHERAL	20.2% 17/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	25.6% 20/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
General disorders PYREXIA	9.5% 8/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Infections and infestations BRONCHITIS	9.5% 8/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	3.8% 3/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Infections and infestations CYTOMEGALOVIRUS INFECTION	13.1% 11/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	5.1% 4/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Infections and infestations NASOPHARYNGITIS	27.4% 23/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	15.4% 12/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Infections and infestations ORAL HERPES	2.4% 2/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Infections and infestations RESPIRATORY TRACT INFECTION	1.2% 1/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	5.1% 4/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Investigations BLOOD CREATININE INCREASED	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	1.3% 1/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Investigations C-REACTIVE PROTEIN INCREASED	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	3.8% 3/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Metabolism and nutrition disorders HYPERCHOLESTEROLAEMIA	8.3% 7/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	3.8% 3/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Metabolism and nutrition disorders HYPERLIPIDAEMIA	10.7% 9/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Metabolism and nutrition disorders HYPERTRIGLYCERIDAEMIA	9.5% 8/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	7.7% 6/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Metabolism and nutrition disorders HYPERURICAEMIA	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	2.6% 2/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Metabolism and nutrition disorders HYPOKALAEMIA	8.3% 7/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	16.7% 13/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	8.3% 7/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	1.3% 1/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders MYALGIA	7.1% 6/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	1.3% 1/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders OSTEOPOROSIS	2.4% 2/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	1.3% 1/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Nervous system disorders HEADACHE	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	9.0% 7/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Respiratory, thoracic and mediastinal disorders COUGH	4.8% 4/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	9.5% 8/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	6.4% 5/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Skin and subcutaneous tissue disorders ACNE	3.6% 3/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	7.7% 6/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Skin and subcutaneous tissue disorders RASH	6.0% 5/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	2.6% 2/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Vascular disorders HYPERTENSION	10.7% 9/84 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.	3.8% 3/78 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.