Trial Outcomes & Findings for SOCRATES: Steroid or Cyclosporine Removal After Transplantation Using Everolimus (NCT NCT00371826)

Last Updated: 2013-08-19

Results Overview

The glomerular filtration rate (GFR) was calculated by the Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)\^ 2 + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

126 participants

Primary outcome timeframe

At Month 12

Results posted on

2013-08-19

Participant Flow

Participant milestones

Participant milestones
Measure	Calcineurin Inhibitor (CNI) Withdrawal Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Core Phase (12 Months) STARTED	49	47	30
Core Phase (12 Months) Modified Intent to Treat (mITT)- Add	46	44	20
Core Phase (12 Months) Modified Intent to Treat (mITT)	27	39	6
Core Phase (12 Months) COMPLETED	25	39	6
Core Phase (12 Months) NOT COMPLETED	24	8	24
Extension Phase (24 Months) STARTED	23	39	5
Extension Phase (24 Months) Intention to Treat - Extenstion (ITT-Ex)	23	39	4
Extension Phase (24 Months) Safety Set	22	40	5
Extension Phase (24 Months) COMPLETED	18	29	3
Extension Phase (24 Months) NOT COMPLETED	5	10	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Calcineurin Inhibitor (CNI) Withdrawal Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Core Phase (12 Months) Adverse Event	15	4	9
Core Phase (12 Months) Abnormal test procedure result(s)	1	0	1
Core Phase (12 Months) Unsatisfactory therapeutic effect	6	3	2
Core Phase (12 Months) Protocol Violation	1	0	1
Core Phase (12 Months) Subject withdrew consent	0	0	3
Core Phase (12 Months) Administrative problems	1	0	8
Core Phase (12 Months) Graft Loss	0	1	0
Extension Phase (24 Months) Adverse Event	4	5	0
Extension Phase (24 Months) Abnormal test procedure result(s)	0	1	0
Extension Phase (24 Months) Unsatisfactory therapeutic effect	0	2	0
Extension Phase (24 Months) Subject withdrew consent	1	2	0
Extension Phase (24 Months) Administrative problems	0	0	2

Baseline Characteristics

SOCRATES: Steroid or Cyclosporine Removal After Transplantation Using Everolimus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol	Total n=126 Participants Total of all reporting groups
Age Continuous	48.4 years STANDARD_DEVIATION 10.17 • n=5 Participants	45.8 years STANDARD_DEVIATION 10.83 • n=7 Participants	43.5 years STANDARD_DEVIATION 10.66 • n=5 Participants	46.3 years STANDARD_DEVIATION 10.63 • n=4 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	13 Participants n=7 Participants	6 Participants n=5 Participants	36 Participants n=4 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	34 Participants n=7 Participants	24 Participants n=5 Participants	90 Participants n=4 Participants

PRIMARY outcome

Timeframe: At Month 12

Population: Modified intent-to-treat (mITT)-Add population: All ITT patients who had a calculated GFR value recorded at Month 12 post-randomization including those collected after discontinuation of study medication and retrospectively collected creatinine and urea data

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=46 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=44 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=20 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (12 Months Analysis)	65.2 mL/min per 1.73 m^2 Standard Deviation 15.52	69.3 mL/min per 1.73 m^2 Standard Deviation 15.18	66.9 mL/min per 1.73 m^2 Standard Deviation 16.22

SECONDARY outcome

Timeframe: At Month 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. Missing values were imputed by last observation carried forward (LOCF) using values beyond Month 6

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=36 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (36 Months Analysis) Month 24 (n= 23, 36, 4)	69.5 mL/min per 1.73 m^2 Standard Error 12.60	71.8 mL/min per 1.73 m^2 Standard Error 16.37	67.0 mL/min per 1.73 m^2 Standard Error 14.72
Calculated Glomerular Filtration Rate (cGFR) After Kidney Transplant to Evaluate Kidney Function (36 Months Analysis) Month 36 (n= 19, 35, 3)	71.6 mL/min per 1.73 m^2 Standard Error 17.50	69.1 mL/min per 1.73 m^2 Standard Error 14.77	61.0 mL/min per 1.73 m^2 Standard Error 11.36

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

A biopsy-proven acute rejection is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (12 Months Analysis)	15 Participants	6 Participants	5 Participants

SECONDARY outcome

Timeframe: At Month 12, 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This population includes also all patients who were randomized but were not treated with study medication.

A biopsy-proven acute rejection is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (36 Months Analysis) At Month 12	4 Participants	4 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (36 Months Analysis) At Month 24	5 Participants	5 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Per Treatment Group (36 Months Analysis) At Month 36	6 Participants	8 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

Composite endpoint of treatment failure includes biopsy-proven acute rejection (BPAR), graft loss, death and loss-to-follow-up. A BPAR is defined as a biopsy graded IA, IB, IIA, IIB, or III as per Banff 97 classification. The allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Composite Endpoint of Treatment Failure (12 Months Analysis)	16 Participants	8 Participants	11 Participants

SECONDARY outcome

Timeframe: At Month 12, 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This population includes also all patients who were randomized but were not treated with study medication.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Composite Endpoint of Treatment Failure (36 Months Analysis) At Month 12	4 Participants	4 Participants	0 Participants
Number of Participants With Composite Endpoint of Treatment Failure (36 Months Analysis) At Month 24	6 Participants	6 Participants	0 Participants
Number of Participants With Composite Endpoint of Treatment Failure (36 Months Analysis) At Month 36	7 Participants	10 Participants	0 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication. For this analysis, only patients with available data were included. The analysis included biopsies of Month 12 visit that were done beyond month 12 cut-off date.

A per-protocol biopsy was performed at Baseline and Month 12 and read by an independent blinded pathologist in order to assess chronic allograft nephropathy. Chronic rejection is characterized by a slow progressive decline in renal function and is typically preceded by the histological picture of chronic allograft nephropathy. The presence of biopsy confirmed Grade I, II or III chronic allograft nephropathy by Banff 97 criteria was assessed on all optional biopsies obtained for clinical suspicion of chronic rejection. Data summarized by 3 categories. "Yes" - Patients with histological evidence of CAN ; "No" - Patients with histological evidence of CAN and "Not Done" - Central protocol defined kidney allograft biopsies were not done.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=30 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=40 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=10 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (12 Months Analysis) YES	8 Participants	6 Participants	2 Participants
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (12 Months Analysis) NO	15 Participants	26 Participants	5 Participants
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (12 Months Analysis) Not Done	7 Participants	8 Participants	3 Participants

SECONDARY outcome

Timeframe: At Month 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. Patients with data available at month 36 were included in this analysis.

Chronic rejection is characterized by a slow progressive decline in renal function and is typically preceded by the histological picture of chronic allograft nephropathy. The presence of biopsy confirmed Grade I, II or III chronic allograft nephropathy by Banff 97 criteria was assessed on all optional biopsies obtained for clinical suspicion of chronic rejection. Data summarized by 3 categories. "Yes" - Patients with histological evidence of CAN ; "No" - Patients with histological evidence of CAN and "Not Done" - Central protocol defined kidney allograft biopsies were not done.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=18 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=31 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=3 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (36 Months Analysis) YES	2 Participants	1 Participants	1 Participants
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (36 Months Analysis) NO	8 Participants	16 Participants	1 Participants
Number of Participants With Histological Evidence Chronic Allograft Nephropathy (CAN) (36 Months Analysis) Not Done	8 Participants	14 Participants	1 Participants

SECONDARY outcome

Timeframe: At Month 12

Based on Banff 97 criteria, sub clinical acute rejection can be: GRADE IA - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IB - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IIA - Cases with significant interstitial infiltration and mild to moderate intimal arteritis (v1). GRADE IIB - Cases with moderate to severe intimal arteritis comprising \>25% of the luminal area (v2). GRADE III - Cases with "transmural" arteritis or fibrinoid change and necrosis of medial smooth muscle cells (v3). "Borderline" category is used when no intimal arteritis is present, but there are foci of mild tubulitis (1 to 4 mononuclear cells/tubular cross section).

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=30 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=40 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=10 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) NO	20 Participants	29 Participants	5 Participants
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) Borderline	2 Participants	2 Participants	2 Participants
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) Grade IA	1 Participants	0 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) Grade IB	0 Participants	1 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) Grade IIA	0 Participants	0 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) Grade IIB	0 Participants	0 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) Grade III	0 Participants	0 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (12 Months Analysis) Not Done	7 Participants	8 Participants	3 Participants

SECONDARY outcome

Timeframe: At Month 36

Based on Banff 97 criteria, sub clinical acute rejection can be: GRADE IA - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>4 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IB - Cases with significant interstitial infiltration (\>25% of parenchyma affected) and foci of moderate tubulitis (\>10 mononuclear cells/tubular cross section or group of 10 tubular cells). GRADE IIA - Cases with significant interstitial infiltration and mild to moderate intimal arteritis (v1). GRADE IIB - Cases with moderate to severe intimal arteritis comprising \>25% of the luminal area (v2). GRADE III - Cases with "transmural" arteritis or fibrinoid change and necrosis of medial smooth muscle cells (v3). "Borderline' category is used when no intimal arteritis is present, but there are foci of mild tubulitis (1 to 4 mononuclear cells/tubular cross section).

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=18 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=31 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=3 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: Grade IIA	0 Participants	0 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: Grade IIB	0 Participants	0 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: Grade III	0 Participants	0 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: Not Done	8 Participants	14 Participants	1 Participants
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: NO	9 Participants	15 Participants	2 Participants
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: Borderline	1 Participants	1 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: Grade IA	0 Participants	1 Participants	0 Participants
Number of Participants With Sub Clinical Acute Rejection (36 Months Analysis) Month 36: Grade IB	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication. Patients with 12 month data on serum creatinine were included in this analysis.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=33 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=43 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=11 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Mean Serum Creatinine (12 Months Analysis)	118.9 umol/L Standard Deviation 31.59	161.0 umol/L Standard Deviation 169.22	148.6 umol/L Standard Deviation 76.84

SECONDARY outcome

Timeframe: At Month 12, 18, 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. Patients with data on creatinine serum creatinine were included in this analysis. Last observation carried forward (LOCF) imputation technique was used.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Mean Serum Creatinine (36 Months Analysis) At Month 12 (n= 23, 39, 4)	112.7 umol/L Standard Deviation 33.38	123.0 umol/L Standard Deviation 33.10	146.8 umol/L Standard Deviation 89.36
Mean Serum Creatinine (36 Months Analysis) At Month 18 (n= 22, 36, 4)	113.6 umol/L Standard Deviation 34.56	121.4 umol/L Standard Deviation 35.78	146.3 umol/L Standard Deviation 89.16
Mean Serum Creatinine (36 Months Analysis) At Month 24 (n = 23, 36, 4)	119.9 umol/L Standard Deviation 36.83	123.7 umol/L Standard Deviation 35.20	146.5 umol/L Standard Deviation 78.20
Mean Serum Creatinine (36 Months Analysis) At Month 36 (n= 19, 35, 3)	119.4 umol/L Standard Deviation 47.50	131.8 umol/L Standard Deviation 42.30	176.0 umol/L Standard Deviation 87.28

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication. Patients with 12 month data on creatinine clearance were included in this analysis.

Creatinine clearance were calculated according to the Cockcroft-Gault formula: CrCl (males) = (140-A) × BW/(72 × Cr) CrCl (females) = CrCl (males) × 0.85 where A is age \[years\], BW is body weight \[kg\], and Cr is the serum concentration of creatinine \[mg/dL\]. The Cockcroft-Gault formula estimates creatinine clearance based on serum creatinine level, body weight, and age.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=33 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=43 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=11 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Creatinine Clearance (CrCl) Calculated by the Cockcroft-Gault Formula (12 Months Analysis)	66.1 mL/min Standard Deviation 19.37	67.8 mL/min Standard Deviation 21.85	63.2 mL/min Standard Deviation 21.73

SECONDARY outcome

Timeframe: At Month 12, 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. Patients with data on creatinine clearance were included in this analysis. Last observation carried forward (LOCF) imputation technique was used.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Creatinine Clearance Calculated by the Cockcroft-Gault Formula (36 Months Analysis) At Month 12 (n= 23, 39, 4)	69.8 mL/min Standard Deviation 19.90	71.7 mL/min Standard Deviation 17.68	63.7 mL/min Standard Deviation 10.33
Creatinine Clearance Calculated by the Cockcroft-Gault Formula (36 Months Analysis) At Month 18 (n=22, 36, 4)	69.9 mL/min Standard Deviation 20.16	73.7 mL/min Standard Deviation 19.34	66.2 mL/min Standard Deviation 12.28
Creatinine Clearance Calculated by the Cockcroft-Gault Formula (36 Months Analysis) At Month 24 (n= 23, 36, 4)	65.6 mL/min Standard Deviation 18.83	72.8 mL/min Standard Deviation 20.86	63.7 mL/min Standard Deviation 5.76
Creatinine Clearance Calculated by the Cockcroft-Gault Formula (36 Months Analysis) At Month 36 (n= 23, 39, 4)	66.3 mL/min Standard Deviation 22.30	67.5 mL/min Standard Deviation 16.01	62.7 mL/min Standard Deviation 16.58

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication. Patients with 12 month data on Proteinuria were included in this analysis.

Proteinuria is measured by spot morning urine Albumin/Creatinine Ratio \[ACR\]. When the ACR is more than or equal to 30 mg/mmol then it is known as proteinuria.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=22 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=32 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Mean Urine Albumin/Creatinine Ratio (ACR) as Measurement of Proteinuria (12 Months Analysis)	0.2 mg/mg Standard Deviation 0.27	0.1 mg/mg Standard Deviation 0.12	0.1 mg/mg Standard Deviation 0.02

SECONDARY outcome

Timeframe: At Month 12, 18, 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment in extension period. This also includes all patients who were randomized but were not treated with study medication. Patients with ACR data at particular time point were included for analysis.

Proteinuria is measured by spot morning urine Albumin/Creatinine Ratio \[ACR\]. When the ACR is more than or equal to 30 mg/mmol then it is known as proteinuria.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=18 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=32 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=2 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Mean Urine Albumin/Creatinine Ratio [ACR] as Measurement of Proteinuria (36 Months Analysis) At 12 Month (n = 18, 32, 2)	23.5 mg/mmol Standard Deviation 31.51	8.1 mg/mmol Standard Deviation 13.40	4.8 mg/mmol Standard Deviation 3.80
Mean Urine Albumin/Creatinine Ratio [ACR] as Measurement of Proteinuria (36 Months Analysis) At 18 Month (n= 17, 31, 2)	28.2 mg/mmol Standard Deviation 47.78	8.1 mg/mmol Standard Deviation 12.00	5.3 mg/mmol Standard Deviation 4.12
Mean Urine Albumin/Creatinine Ratio [ACR] as Measurement of Proteinuria (36 Months Analysis) At 24 Month ( n= 16, 29, 1)	30.0 mg/mmol Standard Deviation 51.72	6.6 mg/mmol Standard Deviation 14.69	7.0 mg/mmol Standard Deviation NA One patient data analyzed in this arm, hence no standard deviation available.
Mean Urine Albumin/Creatinine Ratio [ACR] as Measurement of Proteinuria (36 Months Analysis) At 36 Month ( n= 15, 25, 0)	30.6 mg/mmol Standard Deviation 40.18	23.4 mg/mmol Standard Deviation 66.51	NA mg/mmol Standard Deviation NA No patient, hence no data available.

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication. Patients with 12 month data on PTDM were included in this analysis.

The symptoms of post transplant diabetes mellitus (PTDM) and impaired fasting glucose are defined as any of the following conditions: 1. Patients receiving glucose lowering treatment 2. Fasting plasma glucose (FPG) \>= 126 mg/dL on 2 separate occasions 3. Hemoglobin subtype A1c (HbA1c) \> 6.5% 4. Diabetes reported as treatment emergent AE with end date \> Day 15

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=38 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=42 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=25 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis) Any of the above symptoms	19 Participants	10 Participants	8 Participants
Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis) Glucose lowering treatment	10 Participants	9 Participants	5 Participants
Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis) FPG >= 126 mg/dL on 2 separate occasions	6 Participants	0 Participants	5 Participants
Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis) HbA1c > 6.5%	12 Participants	3 Participants	5 Participants
Number of Participants With Post Transplant Diabetes Mellitus (PTDM) and Impaired Fasting Glucose (12 Months Analysis) Diabetes as treatment emergent AE	8 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: At Month 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This also includes patients who were randomized but were not treated with study drug.

The symptoms of new onset diabetes mellitus after transplantation (NODAT) and impaired fasting glucose are defined as any of the following conditions: 1. Patients receiving glucose lowering treatment 2. 2 fasting plasma glucose (FPG) values \>= 126 mg/dL or 2 random plasma glucose (RPG) values \>= 200 mg/dL or FPG value \>= 126 mg/dL and 1 RPG value \>= 200 mg/dL 3. Diabetes reported as treatment emergent AE with end date \> Day 15

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With New Onset Diabetes Mellitus After Transplantation (NODAT) and Impaired Fasting Glucose (36 Months Analysis) Glucose lowering treatment	5 Participants	10 Participants	2 Participants
Number of Participants With New Onset Diabetes Mellitus After Transplantation (NODAT) and Impaired Fasting Glucose (36 Months Analysis) FPG or RPG	3 Participants	2 Participants	1 Participants
Number of Participants With New Onset Diabetes Mellitus After Transplantation (NODAT) and Impaired Fasting Glucose (36 Months Analysis) Diabetes as treatment emergent AE	5 Participants	4 Participants	2 Participants
Number of Participants With New Onset Diabetes Mellitus After Transplantation (NODAT) and Impaired Fasting Glucose (36 Months Analysis) Any of the above symptoms	6 Participants	11 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline, Overall post-baseline up to 12 month

Population: Safety population (SAF): All patients in whom transplantation was performed and who were treated with at least one dose of study medication and had at least one safety/tolerability assessment after randomization. Patients with baseline and overall post baseline up to 12 month assessment for this analysis were included.

Notable abnormal systolic blood pressure is defined as : * Either an increase of \>=30 that results in \>=180 or \>200 (mm/Hg) * OR a decrease of \>=30 that results in \<=90 or \<75 (mm/Hg)from baseline Notable abnormal diastolic blood pressure is defined as : * Either an increase of \>=20 that results in \>=105 or \>115 (mm/Hg) * OR a decrease of \>=20 that results in \<=50 or \<40 (mm/Hg) from baseline

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis) SBP: >=180 mm/Hg or 200 mm/Hg	5 Participants	5 Participants	7 Participants
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis) SBP: < = 90 mm/Hg or < 200 mm/Hg	1 Participants	0 Participants	0 Participants
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis) DBP : >=105 mm/Hg or >115 mm/Hg	3 Participants	6 Participants	5 Participants
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis) DBP: <=50 mm/Hg or <40 mm/Hg	1 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Overall post baseline up to Month 36

Population: Safety population extension (SAF-EX): All patients who entered the extension period, treated with at least one dose of study medication during the extension period and had at least one safety/tolerability assessment after entering the extension period. Patients with baseline and overall post baseline up to month 36 assessment were included.

Notable abnormal systolic blood pressure is defined as : * Either an increase of \>=30 that results in \>=180 or \>200 (mm/Hg) * OR a decrease of \>=30 that results in \<=90 or \<75 (mm/Hg) from baseline Notable abnormal diastolic blood pressure is defined as : * Either an increase of \>=20 that results in \>=105 or \>115 (mm/Hg) * OR a decrease of \>=20 that results in \<=50 or \<40 (mm/Hg) from baseline

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=22 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=40 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=5 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis) SBP: >=180 mm/Hg or 200 mm/Hg	3 Participants	4 Participants	1 Participants
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis) SBP: < = 90 mm/Hg or < 200 mm/Hg	1 Participants	0 Participants	0 Participants
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis) DBP : >=105 mm/Hg or >115 mm/Hg	2 Participants	5 Participants	1 Participants
Number of Participants With Notable Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis) DBP: <=50 mm/Hg or <40 mm/Hg	1 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Erythropoietin Usage (12 Months Analysis)	20 participants	10 participants	8 participants

SECONDARY outcome

Timeframe: Month 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This also includes patients who were randomized but were not treated with study drug.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Erythropoietin Usage (36 Months Analysis)	5 participants	7 participants	2 participants

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication. Only those patients who had completed the QoL assessment for Month 12 were included in this analysis.

SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales. The 8 subscales are: Physical functioning (PF), Role-physical (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Role-emotional (RE) and Mental health (MH). Score for eash sub-scale has been standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=24 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=37 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=5 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) Physical functioning (PF)	78.7 units on a scale Standard Deviation 26.53	76.9 units on a scale Standard Deviation 30.08	82.0 units on a scale Standard Deviation 34.93
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) Role-physical (RP)	72.9 units on a scale Standard Deviation 40.99	78.2 units on a scale Standard Deviation 33.98	100.0 units on a scale Standard Deviation 0.00
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) Bodily pain (BP)	73.6 units on a scale Standard Deviation 30.60	81.5 units on a scale Standard Deviation 19.21	96.8 units on a scale Standard Deviation 7.16
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) General health (GH)	67.1 units on a scale Standard Deviation 22.41	71.2 units on a scale Standard Deviation 15.75	86.8 units on a scale Standard Deviation 12.91
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) Vitality (VT)	62.7 units on a scale Standard Deviation 23.64	72.4 units on a scale Standard Deviation 15.88	85.0 units on a scale Standard Deviation 9.35
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) Social Functioning (SF)	74.5 units on a scale Standard Deviation 30.72	81.1 units on a scale Standard Deviation 21.97	97.5 units on a scale Standard Deviation 5.59
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) Role-emotional (RE)	72.2 units on a scale Standard Deviation 40.13	81.1 units on a scale Standard Deviation 34.73	100.0 units on a scale Standard Deviation 0.00
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (12 Months Analysis) Mental health (MH)	73.3 units on a scale Standard Deviation 21.02	79.1 units on a scale Standard Deviation 14.58	92.8 units on a scale Standard Deviation 7.69

SECONDARY outcome

Timeframe: At Month 24

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This also includes patients who were randomized but were not treated with study drug. Patients with completed SF-36 assessment were included in this analysis.

SF-36 measures impact of disease on overall quality of life (QoL). 36-item survey has 8 subscales. The 8 subscales are : Physical functioning (PF), Role-physical (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Role-emotional (RE) and Mental health (MH). Score for each sub-scale has been standardized with the use of norm-based methods based on assessment of the general U.S. population free of chronic conditions. Scores range from 1-100 with a mean=50 and a standard deviation=10. A higher score indicates less impact on QoL.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=16 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=31 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=2 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) Physical functioning (PF)	84.3 units on a scale Standard Deviation 24.20	87.6 units on a scale Standard Deviation 17.70	90.0 units on a scale Standard Deviation 7.07
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) Role-physical (RP)	75.0 units on a scale Standard Deviation 39.79	77.4 units on a scale Standard Deviation 33.76	100.0 units on a scale Standard Deviation 0.00
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) Bodily pain (BP)	81.6 units on a scale Standard Deviation 20.57	85.0 units on a scale Standard Deviation 21.18	84.0 units on a scale Standard Deviation 0.00
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) General health (GH)	71.6 units on a scale Standard Deviation 24.45	69.8 units on a scale Standard Deviation 16.46	67.0 units on a scale Standard Deviation 0.00
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) Vitality (VT)	70.0 units on a scale Standard Deviation 23.59	72.7 units on a scale Standard Deviation 13.59	60.0 units on a scale Standard Deviation 14.14
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) Social Functioning (SF)	85.9 units on a scale Standard Deviation 20.35	80.6 units on a scale Standard Deviation 23.46	68.8 units on a scale Standard Deviation 26.52
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) Role-emotional (RE)	72.9 units on a scale Standard Deviation 30.35	83.9 units on a scale Standard Deviation 29.65	33.3 units on a scale Standard Deviation 0.00
Mean Short-form 36 Health Survey (SF-36) Score as a Measure of Quality of Life Assessment (36 Months Analysis) Mental health (MH)	77.5 units on a scale Standard Deviation 18.35	77.9 units on a scale Standard Deviation 16.37	62.0 units on a scale Standard Deviation 8.49

SECONDARY outcome

Timeframe: Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

This analysis is reporting number of participants hospitalized for reasons (such as acute rejection, infection, gastrointestinal (GI) events, cardiovascular event, metabolic disorder and Other) other than primary transplantation.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (12 Months Analysis)	34 Participants	31 Participants	13 Participants

SECONDARY outcome

Timeframe: Month 36

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants Hospitalized for Reasons Other Than Primary Transplantation (36 Months Analysis)	16 Participants	30 Participants	1 Participants

SECONDARY outcome

Timeframe: At screening (at day 0 +/- 7 days ), At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

The various employment status reported are: * Employed/self employed full time * Employed part time * Unemployed * Homemaker * Volunteer * Permanently disabled * Non-permanently disable * Retired * Other

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Employed/self employed full time	18 Participants	21 Participants	9 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Employed/self employed full time	6 Participants	14 Participants	2 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Employed part time	9 Participants	7 Participants	4 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Employed part time	3 Participants	5 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Unemployed	10 Participants	8 Participants	10 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Unemployed	6 Participants	1 Participants	6 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Homemaker	3 Participants	5 Participants	5 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12 : Homemaker	2 Participants	5 Participants	2 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Volunteer	1 Participants	0 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Volunteer	1 Participants	0 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Permanently disabled	2 Participants	2 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Permanently disabled	1 Participants	2 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Non-permanently disabled	1 Participants	2 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Non-permanently disabled	1 Participants	0 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Retired	4 Participants	2 Participants	1 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Retired	1 Participants	2 Participants	0 Participants
Number of Participants With Employment Status (12 Months Analysis) Screening visit: Other	1 Participants	0 Participants	1 Participants
Number of Participants With Employment Status (12 Months Analysis) Month 12: Other	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At screening (at day 0 +/- 7 days ), At Month 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This population includes also all patients who were randomized but were not treated with study medication.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Employed/self employed full time	5 Participants	10 Participants	1 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36: Employed/self employed full time	4 Participants	10 Participants	1 Participants
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Employed part time	4 Participants	7 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36: Employed part time	3 Participants	4 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Unemployed	5 Participants	7 Participants	1 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36: Unemployed	3 Participants	6 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Homemaker	3 Participants	3 Participants	1 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36 : Homemaker	3 Participants	3 Participants	1 Participants
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Permanently disabled	0 Participants	1 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36: Permanently disabled	0 Participants	1 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Non-permanently disabled	0 Participants	1 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36: Non-permanently disabled	0 Participants	1 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Retired	0 Participants	2 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36: Retired	0 Participants	2 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Screening visit: Other	1 Participants	0 Participants	0 Participants
Number of Participants With Employment Status (36 Months Analysis) Month 36: Other	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

Patients with any wound healing problem such as infection related to kidney surgery, dehiscence, lymphocele, hernia, seroma, hematoma, ureteral anastomotic complication and other were reported in this analysis.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Wound Problems(12 Months Analysis) Any wound healing problem	16 Participants	15 Participants	9 Participants
Number of Participants With Wound Problems(12 Months Analysis) Infection related to kidney surgery	2 Participants	4 Participants	3 Participants
Number of Participants With Wound Problems(12 Months Analysis) Dehiscence	3 Participants	2 Participants	2 Participants
Number of Participants With Wound Problems(12 Months Analysis) Lymphocele	3 Participants	4 Participants	3 Participants
Number of Participants With Wound Problems(12 Months Analysis) Hernia	3 Participants	2 Participants	1 Participants
Number of Participants With Wound Problems(12 Months Analysis) Seroma	4 Participants	9 Participants	3 Participants
Number of Participants With Wound Problems(12 Months Analysis) Hematoma	4 Participants	0 Participants	2 Participants
Number of Participants With Wound Problems(12 Months Analysis) Ureteral anastomotic complication	2 Participants	1 Participants	1 Participants
Number of Participants With Wound Problems(12 Months Analysis) Other	3 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: At Month 12, 24 and 36

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Any Wound Problems (36 Months Analysis) At Month 24	9 Participants	13 Participants	2 Participants
Number of Participants With Any Wound Problems (36 Months Analysis) At Month 12	6 Participants	11 Participants	2 Participants
Number of Participants With Any Wound Problems (36 Months Analysis) At Month 36	10 Participants	13 Participants	2 Participants

SECONDARY outcome

Timeframe: Overall post baseline up to month 12

Population: Safety population (SAF): All patients in whom transplantation was performed and who were treated with at least one dose of study medication and had at least one safety/tolerability assessment after randomization. Patients with serum lipid assessment anytime post baseline up to 12 month were included in this analysis.

Notable abnormal total cholesterol is defined as : High: \>= 9.1 mmol/L , normal range is 0.00 - 5.17 mmol/L Notable abnormal triglycerides is defined as : High: \>= 8.5 mmol/L, normal range is 0.30 - 2.00 mmol/L

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=48 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis) Total Cholesterol: High (n = 48, 47,30)	6 Participants	0 Participants	3 Participants
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (12 Months Analysis) Triglycerides : High (n= 48, 46, 30)	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Overall Post Baseline up to month 36

Population: Safety population extension (SAF-EX): All patients who entered the extension period, treated with at least one dose of study medication during the extension period and had at least one safety/tolerability assessment after entering the extension period. Patients with serum lipid assessment anytime post baseline up to 36 month were included .

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=22 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=40 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=5 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis) Triglycerides : High	0 Participants	1 Participants	0 Participants
Number of Participants With Notable Abnormalities in Total Cholesterol and Triglycerides as Measurement of Effect of Treatment on Cardiovascular Health (36 Months Analysis) Total Cholesterol: High	6 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Antibody-mediated Rejection Per Treatment Group (12 Months Analysis)	5 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: At Month 12, 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This population includes also all patients who were randomized but were not treated with study medication.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Antibody-mediated Rejection Per Treatment Group (36 Months Analysis) At Month 12	1 Participants	0 Participants	0 Participants
Number of Participants With Antibody-mediated Rejection Per Treatment Group (36 Months Analysis) At Month 24	1 Participants	0 Participants	0 Participants
Number of Participants With Antibody-mediated Rejection Per Treatment Group (36 Months Analysis) At Month 36	1 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

The influence of demographic characteristics and comorbidities on incidence of BPAR were analyzed in the following way: Demographic characteristics were age (\<55 years, ≥55 years), Expanded criteria Donor (ECD) organ (donor age \>60 years or donor non heart-beating and donor age \>50), gender, living vs. deceased donor, Body Mass Index (BMI) classes (underweight \<18.5, normal 18.5 - \<25.0, overweight 25.0 - \<30.0, obesity 30.0 and above), years on dialysis before transplantation (\<1, 1-5, \>5 years). Comorbidities were diabetes, hypertension, cardiovascular diseases/events, nephrosclerosis, glomerulonephritis/glomerular disease, polycystic disease, and Cytomegalovirus status.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Nephrosclerosis: No	15 Participants	6 Participants	4 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Age < 55 years	11 Participants	5 Participants	4 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Age > = 55 years	4 Participants	1 Participants	1 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) ECD Organ	3 Participants	0 Participants	2 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) NO ECD Organ	12 Participants	6 Participants	3 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Male	11 Participants	6 Participants	4 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Female	4 Participants	0 Participants	1 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Living donor	9 Participants	6 Participants	2 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Deceased donor	6 Participants	0 Participants	3 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) BMI < 18.5	0 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) BMI 18.5 - <25	5 Participants	2 Participants	3 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) BMI 25 - <30	8 Participants	3 Participants	1 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) BMI >= 30	2 Participants	0 Participants	1 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Years on dialysis before transplantation: None	1 Participants	0 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) < 1 Year on dialysis before transplantation	3 Participants	3 Participants	1 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) 1 - 5 Years on dialysis before transplantation	8 Participants	1 Participants	2 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) > 5 Years on dialysis before transplantation	3 Participants	2 Participants	2 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Diabetes mellitus: No	10 Participants	4 Participants	4 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Diabetes mellitus: Yes	5 Participants	2 Participants	1 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Hypertension: No	2 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Hypertension: Yes	13 Participants	5 Participants	5 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Cardiovascular disease : No	4 Participants	3 Participants	2 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Cardiovascular disease: Yes	11 Participants	3 Participants	3 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Nephrosclerosis: Yes	0 Participants	0 Participants	1 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Glomerulonephritis/glomerular disease : No	8 Participants	5 Participants	3 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Glomerulonephritis/glomerular disease: Yes	7 Participants	1 Participants	2 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Cytomegalovirus : Negative	2 Participants	2 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (12 Months Analysis) Cytomegalovirus : Positive	13 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: At Month 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This population includes also all patients who were randomized but were not treated with study medication

The influence of demographic characteristics and comorbidities on incidence of BPAR were analyzed in the following way: Demographic characteristics were age (\<55 years, ≥55 years), Expanded Criteria Donor \[ECD\] organ (donor age \>60 years or donor non heart-beating and donor age \>50), gender, living vs. deceased donor, Body Mass Index (BMI) classes (underweight \<18.5, normal 18.5 - \<25.0, overweight 25.0 - \<30.0, obesity 30.0 and above), years on dialysis before transplantation (\<1, 1-5, \>5 years). Comorbidities were diabetes, hypertension, cardiovascular diseases/events, nephrosclerosis, glomerulonephritis/glomerular disease, polycystic disease, and Cytomegalovirus status.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Age < 55 years	6 Participants	7 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Age > = 55 years	0 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) ECD Organ	0 Participants	0 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) NO ECD Organ	6 Participants	8 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Male	4 Participants	7 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Female	2 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Living donor	5 Participants	6 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Deceased donor	1 Participants	2 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) BMI < 18.5	1 Participants	0 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) BMI 18.5 - <25	1 Participants	3 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) BMI 25 - <30	4 Participants	4 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) BMI >= 30	0 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Years on dialysis before transplantation: None	0 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) < 1 Year on dialysis before transplantation	3 Participants	4 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) 1 - 5 Years on dialysis before transplantation	2 Participants	2 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) > 5 Years on dialysis before transplantation	1 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Diabetes mellitus: No	3 Participants	6 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Diabetes mellitus: Yes	3 Participants	2 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Hypertension: No	1 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Hypertension: Yes	5 Participants	7 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Cardiovascular disease : No	3 Participants	5 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Cardiovascular disease: Yes	3 Participants	3 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Nephrosclerosis: No	6 Participants	7 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Nephrosclerosis: Yes	0 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Glomerulonephritis/glomerular disease : No	4 Participants	7 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Glomerulonephritis/glomerular disease: Yes	2 Participants	1 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Cytomegalovirus : Negative	1 Participants	4 Participants	0 Participants
Number of Participants With Biopsy Proven Acute Rejection (BPAR) Influenced by Demographic Characteristics and Morbidities (36 Months Analysis) Cytomegalovirus : Positive	5 Participants	4 Participants	0 Participants

SECONDARY outcome

Timeframe: At Month 12

Population: Intent-to-treat (ITT) population: All patients who were randomized. This population also included all patients who were randomized but were not treated with study medication.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=49 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=47 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=30 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Patient Survival and Graft Survival (12 Months Analysis) Patient Survival	49 Participants	46 Participants	30 Participants
Number of Patient Survival and Graft Survival (12 Months Analysis) Graft Survival	49 Participants	45 Participants	30 Participants

SECONDARY outcome

Timeframe: At Month 12, 24 and 36

Population: Intent-to-treat population extension (ITT-EX): All patients who were randomized, entered the extension period, and had at least one efficacy assessment after entering the extension period. This population includes also all patients who were randomized but were not treated with study medication.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=23 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=39 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=4 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Number of Patient Survival and Graft Survival (36 Months Analysis) Month 12: Patient Survival	23 Participants	39 Participants	4 Participants
Number of Patient Survival and Graft Survival (36 Months Analysis) Month 12: Graft Survival	23 Participants	39 Participants	4 Participants
Number of Patient Survival and Graft Survival (36 Months Analysis) Month 24: Patient Survival	23 Participants	39 Participants	4 Participants
Number of Patient Survival and Graft Survival (36 Months Analysis) Month 24: Graft Survival	23 Participants	39 Participants	4 Participants
Number of Patient Survival and Graft Survival (36 Months Analysis) Month 36: Patient Survival	23 Participants	39 Participants	4 Participants
Number of Patient Survival and Graft Survival (36 Months Analysis) Month 36: Graft Survival	23 Participants	39 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 2, Month 24

Population: Safety population extension (SAF-EX): All patients who entered the extension period, who were treated with at least one dose of study medication during the extension period and had at least one safety/tolerability assessment after entering the extension period. Patients with week 2 and month 24 assessment for this analysis were included.

Measurements of bone mineral density (BMD) by Dual Energy X-ray Absorptiometry (DEXA) were done at Week 2 and Month 24. Change in BMD between week 2 and Month 24 were done for neck of femur and lumbar spine.

Outcome measures

Outcome measures
Measure	Calcineurin Inhibitor (CNI) Withdrawal n=19 Participants Every randomized patient in this group received Day 1 - Day 14: cyclosporine as Calcineurin Inhibitor (CNI) 5 mg/kg twice daily (b.i.d.), dose adjusted to achieve C2 target of 1,500 ng/mL (range 1,400-1,600 ng/mL) + mycophenolate sodium (MPA)720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg/day prednisone Day 15 - Day 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg/day Day 61 - Day 120: everolimus dose adjusted to achieve target 6-10 ng/mL + cyclosporine 25% dose reduction per fortnight, to be discontinued by day 120 as per protocol (or commence reduction by day 120 at discretion of investigator, to be completed within 2 months of commencement) + prednisone 10-30mg/day Day 121 - Month 36: everolimus dose adjusted to achieve target 8-12 ng/mL + prednisone 5-10 mg/day	CNI+MPA+ Steroid n=33 Participants Patients randomized to this group received: Day 1 - Month 36: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve the protocol defined C2 Targets + mycophenolate sodium 720mg b.i.d. + Methylprednisone/prednisone 500mg intra-operatively, 250mg on day 1, 10-30mg prednisone per day until month 12 (as per local practice), 5-10mg/day months 13-36.	Steroid Withdrawal n=2 Participants Every randomized patient in this group received Day 1 -14: cyclosporine 5 mg/kg b.i.d., dose adjusted to achieve C2 target as per protocol + mycophenolate sodium (MPA) 720 mg b.i.d. + methylprednisone/prednisone 500 mg intra-operatively, 250 mg on day 1, then 10-30 mg prednisone per day Day 15 - 60: everolimus 1.5 mg b.i.d. to achieve target 6-10 ng/mL + cyclosporine decrease dose as per protocol guideline + MPA 720 mg b.i.d. until everolimus trough \>6 ng/mL, then MPA was stopped + prednisone 10-30mg per day Day 61 - 120: Everolimus dose adjusted + cyclosporine adjust dose according protocol guideline (or commence reduction by day 120 at discretion of Investigator, to be completed within 2 months of commencement) + gradual withdrawal of prednisone by 1 mg/week to be discontinued by Day 120. Day 121 - Month 36: At Day 121, Month 7 and Month 13 Everolimus dose was adjusted to achieve target 6-10 ng/mL + Cyclosporine adjust dose to achieve C2 target as per protocol
Change in Bone Mineral Density Between Week 2 and Month 24 (36 Months Analysis) Neck of Femur (Month 24- Week 2)	0.2 g/cm^2 Standard Deviation 0.91	-0.1 g/cm^2 Standard Deviation 0.06	-0.1 g/cm^2 Standard Deviation 0.05
Change in Bone Mineral Density Between Week 2 and Month 24 (36 Months Analysis) Lumbar Spine (Month 24 - Week 2)	-0.0 g/cm^2 Standard Deviation 0.14	-0.1 g/cm^2 Standard Deviation 0.10	-0.0 g/cm^2 Standard Deviation 0.07

Adverse Events

Calcineurin Inhibitor (CNI) Withdrawal

Serious events: 33 serious events

Other events: 47 other events

Deaths: 0 deaths

CNI+MPA+ Steroid

Serious events: 36 serious events

Other events: 48 other events

Deaths: 0 deaths

Steroid Withdrawal

Serious events: 16 serious events

Other events: 30 other events

Deaths: 0 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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER