Efficacy Regarding Renal Function of Everolimus in Combination With Specific Standard Immunosuppressive Regimen Lung Transplant Recipients

Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at 12 months The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)\^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1

Time frame: Month 12

Population: Full Analysis Set multiple imputation (FAS MI) consisted of all patients as randomized that received at least 1 dose of study drug \& had a valid baseline assessment of the primary efficacy variable. Missing values was dealt with by multiple imputation (MI)

Adherence to target ranges of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Adherence to target ranges of everolimus at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Adherence to target ranges of Tacrolimus at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Calculated Glomerular Filtration Rate (cGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) at Month 1, 3, 6, 9 and 12. The CKD-EPI equation, expressed as a single equation, is GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)\^-1.209 × 0.993Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1

Time frame: Month 1, 3, 6, 9, 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Calculated Glomerular Filtration Rate (cGFR) according to Cockcroft-Gault at Month 1, 3, 6, 9, 12 For men: GFR=(140-Age) x Body weight (kg) / 72 x Serum Creatinine (mg/dl) For women: GFR=0.85 (140 -Age) x Body weight(kg)/ 72 x Serum Creatinine (mg/dl)

Time frame: Month 1, 3, 6, 9, 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Calculated Glomerular Filtration Rate (cGFR) according to Cystatin C-based Hoek's formula at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula at Month 1, 3, 6, 9, 12 cGFR (in mL/min/1.73 m2) = 186.3\*(C-1.154)\*(A-0.203)\*G\*R where C = the serum concentration of creatinine (mg/dL), A = age (years), G = 0.742 when gender is female, otherwise G = 1, R = 1.21 when race is black, otherwise R = 1.

Time frame: Month 1, 3, 6, 9, 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Exercise capacity (6MWT) at Month 6 and Month 12 Measured by the Borg Scale. THE BORG SCALE 0 is Nothing at all, 0.5 is Very, very slight (just noticeable); 1 is Very slight, 2 is Slight (light); 3 is Moderate; 4 is Somewhat severe; 5 is Severe (heavy), 7 is Very severe, 10 is Very, very severe (maximal)The higher the Borg score implies increased shortness of breath and/or increased fatigue.

Time frame: Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

HDL Cholesterol levels at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Incidence of acute rejection episodes at Month 6 and Month 12. This table counts multiple occurrences of rejection in the same patient as different incidents. Every incident is associated with both an A and a B classification. Classification A: Acute Rejection Grade 0 - none, Grade 1-minimal, Grade 2- mild, Grade 3-moderate, Grade 4-Severe; Classification B: Airway Inflammation-Grade 0-none, Grade 1R-low grade, Grade 2R-high grade, Grade X-ungradeable

Time frame: Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Incidence of bacterial, viral, and fungal infections at Month 12

Time frame: Month 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Incidence of Bronchiolitis obliterans syndrome (BOS) at Month 6 and Month 12 BOS 0 is FEV1 \> 90% of baseline and FEF25-75% \> 75% of baseline; BOS 0-p is FEV1 81-90% of baseline and/or FEF25-75% ≤ 75% of baseline; BOS 1 is FEV1 66-80% of baseline; BOS 2 is FEV1 51-65% of baseline; BOS 3 is FEV1 ≤ 50% of baseline

Time frame: Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Incidence of death at Month 6 and Month 12

Time frame: Month 6, Month 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Incidence of Diabetes Mellitus up to Month 12

Time frame: up to Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Incidence of graft loss/re-transplantation at Month 6 and Month 12

Time frame: Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Incidence of patients experiencing a decline in GFR of \< 10, 10-15, 15-20, 20-25 and \> 25 mL/min from Baseline to Month 6 and 12calculated by the CKD-EPI method. Participants are counted in each decline level observed for that participant; this means participants may be counted in more than 1 decline level.

Time frame: Baseline, Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Incidence of renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required

Time frame: Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Incidence of treated of arterial hypertension up to Month 12

Time frame: up to Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

LDL Cholesterol levels at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Quality of Life (QoL, SF36) at Month 6 and Month 12 Scores can range from a minimum of 0 (maximum disability) to a maximum of 100 (no disability).

Time frame: Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.

Time to renal replacement therapy at Month 6 and Month 12: There were no incidences in either group where renal replacement therapy was required

Time frame: Month 6, Month 12

Population: Full Analysis Set (FAS) consisted of all patients as randomized that received at least 1 dose of study drug and had a valid baseline assessment of the primary efficacy variable. The outcome could not be analyzed because there were no incidences of renal replacement therapy

Total Cholesterol levels at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Triglyceride levels at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Trough levels of Cyclosporine A (CsA) at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Trough levels of everolimus at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.

Trough levels of Tacrolimus at Month 1, 3, 6, 9, 12

Time frame: Month 1, 3, 6, 9, 12

Population: Safety Set consisted of all patients that received at least 1 dose of study drug and had at least 1 post-baseline safety assessment. Patients were analyzed according to treatment received. Of note, the statement that a patient had no AEs also constituted a safety assessment.