Trial Outcomes & Findings for Efficacy of Everolimus in Combination With Tacrolimus in Liver Transplant Recipients (NCT NCT01551212)

NCT ID: NCT01551212

Last Updated: 2019-05-10

Results Overview

The estmated GFR was calculated using MDRD-4 formula (Modification of Diet in Renal Disease Study Group).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

339 participants

Primary outcome timeframe

month 12

Results posted on

2019-05-10

Participant Flow

In total, 642 patients were screened for study eligibility at 15 study centers in Germany. 339 patients were randomized out of which 333 received study treatment and were included in the analyses.

Patients were screened for eligibility prior to liver transplantation (LTx). The study treatment started after a run-in period that ended on the day of randomization, scheduled at Day 7-21 post-LTx. Patients may have been initiated on an optional induction therapy, MMF, TAC at investigators' discretion.

Participant milestones

Participant milestones
Measure	Everolimus/Tacrolimus Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus Tacrolimus (C0-h: 6-10 ng/ml)
Overall Study STARTED	171	168
Overall Study Full Anylsis Set (FAS)	169	164
Overall Study Safety Set	169	164
Overall Study Per Protocol Set (PP)	110	101
Overall Study COMPLETED	166	148
Overall Study NOT COMPLETED	5	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus/Tacrolimus Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus Tacrolimus (C0-h: 6-10 ng/ml)
Overall Study Graft loss/Retransplantation	0	1
Overall Study Administrative problems	1	2
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	0	7
Overall Study Death	2	4
Overall Study Never Received Study Treatment	2	4

Baseline Characteristics

Full Analysis Set (FAS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus/Tacrolimus n=169 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 Participants Tacrolimus (C0-h: 6-10 ng/ml)	Total n=333 Participants Total of all reporting groups
Age, Continuous	53.68 Years STANDARD_DEVIATION 9.38 • n=93 Participants • Full Analysis Set (FAS)	53.46 Years STANDARD_DEVIATION 9.64 • n=4 Participants • Full Analysis Set (FAS)	53.57 Years STANDARD_DEVIATION 9.49 • n=27 Participants • Full Analysis Set (FAS)
Sex: Female, Male Female	36 Participants n=93 Participants	43 Participants n=4 Participants	79 Participants n=27 Participants
Sex: Female, Male Male	133 Participants n=93 Participants	121 Participants n=4 Participants	254 Participants n=27 Participants
Race/Ethnicity, Customized Caucasian	168 Participants n=93 Participants • Full Analysis Set (FAS)	157 Participants n=4 Participants • Full Analysis Set (FAS)	325 Participants n=27 Participants • Full Analysis Set (FAS)
Race/Ethnicity, Customized Black	1 Participants n=93 Participants • Full Analysis Set (FAS)	1 Participants n=4 Participants • Full Analysis Set (FAS)	2 Participants n=27 Participants • Full Analysis Set (FAS)
Race/Ethnicity, Customized Asian	0 Participants n=93 Participants • Full Analysis Set (FAS)	3 Participants n=4 Participants • Full Analysis Set (FAS)	3 Participants n=27 Participants • Full Analysis Set (FAS)
Race/Ethnicity, Customized Other	0 Participants n=93 Participants • Full Analysis Set (FAS)	3 Participants n=4 Participants • Full Analysis Set (FAS)	3 Participants n=27 Participants • Full Analysis Set (FAS)

PRIMARY outcome

Timeframe: month 12

Population: FAS (Full Analysis Set - All Randomized AND Treated Patients) with LOCF (last observation carried forward)

The estmated GFR was calculated using MDRD-4 formula (Modification of Diet in Renal Disease Study Group).

Outcome measures

Outcome measures
Measure	Everolimus/Tacrolimus n=169 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 Participants Tacrolimus (C0-h: 6-10 ng/ml)
Estimated Glomerular Filtration Rate (GFR)	73.46 mL/min Standard Deviation 25.57	71.95 mL/min Standard Deviation 27.17

SECONDARY outcome

Timeframe: month 12

Population: Per Protocol Set (PP)

This was a sensitivity analysis for the primary outcome measure based on the per-protocol set of patients.

Outcome measures

Outcome measures
Measure	Everolimus/Tacrolimus n=110 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=101 Participants Tacrolimus (C0-h: 6-10 ng/ml)
Estimated GFR - PP Set	74.83 mL/min Standard Deviation 25.19	70.65 mL/min Standard Deviation 24.91

SECONDARY outcome

Timeframe: 12 months

Population: FAS

Percentage of Participants with Treated Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death at Month 12

Outcome measures

Outcome measures
Measure	Everolimus/Tacrolimus n=169 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 Participants Tacrolimus (C0-h: 6-10 ng/ml)
Percentage of Participants With Treated Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death	9.5 Percent of Patients	7.9 Percent of Patients

SECONDARY outcome

Timeframe: 12 months

Population: Safety Set

Number of Participants with HCV (hepatitis C virus) assessed as treatment emergent adverse events of special interest

Outcome measures

Outcome measures
Measure	Everolimus/Tacrolimus n=169 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 Participants Tacrolimus (C0-h: 6-10 ng/ml)
Number of Participants With HCV	6 Participants	12 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Safety Set

Incidence of hepatitis C virus (HCV) related fibrosis assessed as treatment emergent adverse events of special interest

Outcome measures

Outcome measures
Measure	Everolimus/Tacrolimus n=169 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 Participants Tacrolimus (C0-h: 6-10 ng/ml)
Incidence of HCV Related Fibrosis	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Safety Set

Incidence of de novo Hepatocellular Carcinoma (HCC) malignancies assessed as treatment emergent adverse events of special interest

Outcome measures

Outcome measures
Measure	Everolimus/Tacrolimus n=169 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 Participants Tacrolimus (C0-h: 6-10 ng/ml)
Incidence of de Novo HCC Malignancies	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Safety Set

Incidence and severity of cytomegalovirus (CMV) viral infections assessed as treatment emergent adverse events of special interest.

Outcome measures

Outcome measures
Measure	Everolimus/Tacrolimus n=169 Participants Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 Participants Tacrolimus (C0-h: 6-10 ng/ml)
Incidence and Severity of CMV Viral Infections. No CMV viral infection	136 Participants	129 Participants
Incidence and Severity of CMV Viral Infections. Asymptomatic	0 Participants	5 Participants
Incidence and Severity of CMV Viral Infections. Mild	16 Participants	20 Participants
Incidence and Severity of CMV Viral Infections. Moderate	13 Participants	9 Participants
Incidence and Severity of CMV Viral Infections. Severe	4 Participants	1 Participants

Adverse Events

Everolimus/Tacrolimus

Serious events: 111 serious events

Other events: 164 other events

Deaths: 3 deaths

Tacrolimus

Serious events: 101 serious events

Other events: 153 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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 the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Everolimus/Tacrolimus n=169 participants at risk Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 participants at risk Tacrolimus (C0-h: 6-10 ng/ml)
Blood and lymphatic system disorders ANAEMIA	2.4% 4/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders BONE MARROW TOXICITY	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders EVANS SYNDROME	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders HYPOCHROMIC ANAEMIA	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders IRON DEFICIENCY ANAEMIA	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders LYMPHOCYTOSIS	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders PANCYTOPENIA	1.8% 3/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders ACUTE MYOCARDIAL INFARCTION	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders ATRIAL FIBRILLATION	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders CARDIOGENIC SHOCK	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders CORONARY ARTERY DISEASE	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders MITRAL VALVE INCOMPETENCE	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders PERICARDIAL EFFUSION	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders SUPRAVENTRICULAR TACHYCARDIA	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	1.8% 3/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders TACHYCARDIA	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders VENTRICULAR EXTRASYSTOLES	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Cardiac disorders VENTRICULAR TACHYCARDIA	1.2% 2/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Ear and labyrinth disorders VERTIGO	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Endocrine disorders GOITRE	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Endocrine disorders TOXIC NODULAR GOITRE	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Eye disorders MYDRIASIS	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ABDOMINAL HERNIA	1.8% 3/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ABDOMINAL PAIN	1.2% 2/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	1.2% 2/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ABDOMINAL PAIN UPPER	1.2% 2/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders APHTHOUS ULCER	1.2% 2/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ASCITES	3.0% 5/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	3.0% 5/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders COLITIS	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders DENTAL CARIES	1.2% 2/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders DIARRHOEA	3.0% 5/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	2.4% 4/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders DUODENAL ULCER	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ENTEROCOLITIS	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders FAECES DISCOLOURED	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders GASTRIC ULCER HAEMORRHAGE	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders GASTRITIS	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders GASTROINTESTINAL ANGIODYSPLASIA HAEMORRHAGIC	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders GASTROINTESTINAL HAEMORRHAGE	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders GASTROINTESTINAL INFLAMMATION	0.00% 0/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders GASTROINTESTINAL NECROSIS	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.61% 1/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders IMPAIRED GASTRIC EMPTYING	0.59% 1/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months

Other adverse events
Measure	Everolimus/Tacrolimus n=169 participants at risk Tacrolimus minimization arm. Everolimus (C0-h: 3-8 ng/mL) + tacrolimus (C0-h: \< 5 ng/mL)	Tacrolimus n=164 participants at risk Tacrolimus (C0-h: 6-10 ng/ml)
Blood and lymphatic system disorders ANAEMIA	13.0% 22/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	12.2% 20/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders LEUKOPENIA	26.6% 45/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	7.3% 12/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Blood and lymphatic system disorders THROMBOCYTOPENIA	14.8% 25/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	2.4% 4/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ABDOMINAL PAIN	13.6% 23/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	10.4% 17/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ABDOMINAL PAIN UPPER	8.9% 15/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	6.7% 11/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders APHTHOUS ULCER	6.5% 11/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	0.00% 0/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders ASCITES	11.8% 20/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	7.9% 13/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders CONSTIPATION	7.7% 13/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	6.1% 10/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders DIARRHOEA	25.4% 43/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	23.8% 39/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders NAUSEA	13.0% 22/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	7.9% 13/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Gastrointestinal disorders VOMITING	9.5% 16/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	7.3% 12/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
General disorders IMPAIRED HEALING	14.2% 24/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	6.1% 10/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
General disorders OEDEMA PERIPHERAL	22.5% 38/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	9.1% 15/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
General disorders PYREXIA	11.8% 20/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	5.5% 9/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Hepatobiliary disorders CHOLANGITIS	5.3% 9/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	1.2% 2/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Hepatobiliary disorders HEPATIC CYST	5.9% 10/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	1.8% 3/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Hepatobiliary disorders HEPATIC STEATOSIS	7.1% 12/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	4.9% 8/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Infections and infestations CYTOMEGALOVIRUS INFECTION	14.2% 24/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	17.1% 28/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Infections and infestations URINARY TRACT INFECTION	17.8% 30/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	14.6% 24/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	24.3% 41/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	17.7% 29/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Injury, poisoning and procedural complications INCISIONAL HERNIA	20.7% 35/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	6.1% 10/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Injury, poisoning and procedural complications PROCEDURAL PAIN	3.0% 5/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	5.5% 9/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Investigations BLOOD CREATININE INCREASED	12.4% 21/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	12.8% 21/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Investigations BODY TEMPERATURE INCREASED	3.6% 6/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	5.5% 9/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Investigations C-REACTIVE PROTEIN INCREASED	10.7% 18/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	5.5% 9/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Investigations GAMMA-GLUTAMYLTRANSFERASE INCREASED	5.9% 10/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	7.3% 12/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Investigations HEPATIC ENZYME INCREASED	5.3% 9/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	7.9% 13/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Investigations TRANSAMINASES INCREASED	5.3% 9/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	4.9% 8/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders DIABETES MELLITUS	6.5% 11/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	4.9% 8/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders HYPERCHOLESTEROLAEMIA	17.8% 30/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	5.5% 9/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders HYPERKALAEMIA	7.7% 13/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	10.4% 17/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders HYPERLIPIDAEMIA	8.9% 15/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	1.2% 2/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders HYPERTRIGLYCERIDAEMIA	10.7% 18/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	4.9% 8/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders HYPERURICAEMIA	5.9% 10/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	4.9% 8/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders HYPOKALAEMIA	6.5% 11/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	4.9% 8/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders IRON DEFICIENCY	6.5% 11/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	3.0% 5/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Metabolism and nutrition disorders VITAMIN D DEFICIENCY	6.5% 11/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	6.1% 10/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Musculoskeletal and connective tissue disorders ARTHRALGIA	5.3% 9/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	4.9% 8/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Musculoskeletal and connective tissue disorders BACK PAIN	10.1% 17/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	7.3% 12/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	4.1% 7/169 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months	5.5% 9/164 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 12 months