Study Evaluating The Effect Of Ramipril On Urinary Protein Excretion In Renal Transplant Patients Converted To Sirolimus

The event for each participant was defined as the initiation of losartan while on SRL and ramipril/placebo combination therapy. Participants who started losartan prior to SRL administration were not counted as events. Percentage was estimated using Kaplan-Meier method for time to event data.

Defined as the time from the first dose of SRL administration to the first dose escalation of randomized test article (ramipril or placebo; in weeks), or censored on the day that a participant stopped the combination of SRL and randomized test article (ramipril or placebo) if the participants did not experience any ramipril/placebo dose escalation following conversion to SRL. Dose-escalation was defined as an increase in total daily dose of ramipril/placebo compared to Day 1 post conversion. Percentage was estimated using Kaplan-Meier method for time to event data.

Spot urine sample of protein and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.

Spot urine sample of albumin and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.

The U alb/c and U p/c must have been collected on the same day to be counted as the numerator.

U p/c was measured in milligrams per milligram (mg/mg). The baseline U p/c values were the last values of the pre-SRL conversion period.

U alb/c was measured in mg/mg. Baseline U alb/c values were the last values of the pre-SRL conversion period.

Defined as the percentage of participants who stop SRL (as test article) between the first day of SRL and either Week 24 or Week 52 following conversion to SRL. If a participant had a >14 day gap in SRL use, the stop date of SRL was the date of the last SRL use before it was re-initiated. Participants who early terminate SRL at Week 24 were defined as having SRL stop day less than or equal to (≤) Day 190 (selected as the midpoint between Weeks 24 and 30). Participants who early terminate SRL at Week 52 were defined as having SRL stop day ≤Day 337 (selected as the midpoint between Weeks 44 and 52).

Calculated in millimeters per minute per 1.73 square meters (mL/min/1.73m^2). Age and corresponding creatinine at each visit (Weeks 12, 24, and 52) were used to calculate GFR.

Baseline fraction was the last value of the pre-SRL conversion period. Only the last value of U p/c or U alb/c was used for analysis if multiple measurements occurred in the same data anlysis interval. Fraction of albumin and protein was calculated only when urine protein was 6.2 mg/dL or higher. For urine albumin, if the value was reported as '<xx.x', the numerical portion of the value was used in the calculation of fraction of albumin and protein.

BP values of potential clinical importance were recorded and categorized as follows: diastolic BP (DBP) ≤50 millimeters of mercury (mmHg) or ≥110 mmHg and systolic BP (SBP) ≤90 mmHg and ≥180 mmHg. Data were summarized for the on-therapy period and the off-therapy period and for the pre-SRL period.

Cmin,TN was determined for SRL using the area method for the intervals: 0-2 weeks, >2-4 weeks, >4-12 weeks, >12-24 weeks, >24-36 weeks and >36-52 weeks using the equation:Cmin,TN = AUCi-j/timej-timeiwhere AUC is the area under the concentration-time curve, i is the beginning of the interval and j is the end of the interval. Cmin,TN was calculated for participants who did not dropout of studies, but were missing concentrations at the interval endpoints by carrying the last observed concentration forward to the interval endpoint.

Parameters assessed included (all fasting) total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-densitylipoprotein cholesterol (HDL-C).

BCAR was defined according to updated Banff criteria (1997)for renal allograft rejection. The time to the first BCAR was defined as the date of first BCAR to the date of the first dose of SRL (in weeks). Participants without BCAR were censored at the time of withdrawal from the study.

BCAR was defined according to updated Banff criteria (1997)for renal allograft rejection. Participants without BCAR were censored at the time of withdrawal from the study. Defined as the first BCAR occurring on therapy following conversion to SRL based on the mITT population. Time to first BCAR was defined as the date of first BCAR to date of the first dose of SRL (in weeks). Percentages were estimated using the Kaplan-Meier method for time to event data.

Severity was summarized by type (antibody versus T-cell) and by phase: post-SRL (where both on-therapy and off-therapy events are included) and post-SRL (on-therapy). BCAR was categorized using Banff criteria as antibody-mediated (AM) or T-cell. AM BCAR severity was graded as Grade I (mild), Grade II (moderate [mod]), and Grade III (severe). T-cell BCAR severity was graded as 'Grade Ia, Ib (mild), Grade IIa, IIb (mod), and Grade III (severe). If a participant had both T-cell BCAR and antibody-mediated BCAR on the first rejection, the participant was counted in each category. For participants with T-cell BCAR (post-SRL and post-SRL On -Therapy) the p-value could not be calculated and all events were mild in severity.

Graft loss was defined as physical loss (nephrectomy orretransplantation), functional loss (requiring dialysis for ≥56days with no return of graft function), or death.

Includes treatment-emergent adverse events based on categorization by the investigator as 'infection', regardless of the event preferred term in Medical Dictionary for Regulatory Activities (MedDRA.)

Includes treatment-emergent adverse events based on categorization by the investigator as angioedema, regardless of the event preferred term in MedDRA.

Includes treatment-emergent adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferredterm in MedDRA.

Hyperkalemia defined as serum potassium >5.6 millimoles per liter (mmol/L)