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Trial record 56 of 537 for:    "Skin cancer"

Study Evaluating the Effect of Sirolimus on Non-Melanoma Skin Cancer in Kidney Transplant Recipients

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ClinicalTrials.gov Identifier: NCT00129961
Recruitment Status : Completed
First Posted : August 12, 2005
Results First Posted : March 23, 2012
Last Update Posted : April 11, 2012
Sponsor:
Information provided by (Responsible Party):
Wyeth is now a wholly owned subsidiary of Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Skin Neoplasms
Kidney Transplantation
Interventions Drug: sirolimus
Drug: cyclosporine or tacrolimus
Enrollment 86
Recruitment Details Subjects were recruited in Australia, New Zealand and North America from August 2005 (first subject randomized September 2005) through October 2007.
Pre-assignment Details Screening and baseline evaluations were performed within 4 weeks prior to randomization. Randomization assignments by site were stratified by the number of new NMSC lesions in the 12 months prior to enrollment (0-5 lesions vs 6-20 lesions).
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted. Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Period Title: Overall Study
Started 39 47
Completed 20 24
Not Completed 19 23
Reason Not Completed
Adverse Event             1             0
Death             1             1
Withdrawal by Sponsor             14             20
Physician Decision             1             0
Withdrawal by Subject             2             1
Missing Record             0             1
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen Total
Hide Arm/Group Description All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted. Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated. Total of all reporting groups
Overall Number of Baseline Participants 39 47 86
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 39 participants 47 participants 86 participants
59.08
(36 to 76)
58.98
(37 to 78)
59.02
(36 to 78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants 47 participants 86 participants
Female
8
  20.5%
13
  27.7%
21
  24.4%
Male
31
  79.5%
34
  72.3%
65
  75.6%
Stratification Group  
Measure Type: Number
Unit of measure:  Subjects
Number Analyzed 39 participants 47 participants 86 participants
0-5 Lesions in 12 months prior 33 39 72
6-20 Lesions in 12 months prior 6 8 14
Time from Current Transplantation to Randomization  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 39 participants 47 participants 86 participants
114.98  (57.63) 109.57  (55.08) 112.02  (55.98)
1.Primary Outcome
Title New Biopsy-Confirmed Nonmelanoma Skin Cancer (NMSC) Lesions Per Subject Per Year
Hide Description The number of new biopsy-confirmed NMSC lesions per subject per year was calculated by summarizing the total number of new BCC and SCC lesions reported over the observation period and standardizing it to an annual rate by multiplying by 365 and dividing by days on study.
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: Standardized Yearly Rate of NMSC
1.31 2.48
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments Poisson regression was used to model NMSC counts using the years in study as an offset. The generalized estimated equations (GEE) approach was used to estimate parameters and compare treatment differences.
Method Poisson regression
Comments Adjusted by baseline strata; Poisson model = strata + treatment.
2.Secondary Outcome
Title Time to First Biopsy Confirmed New NMSC Lesion.
Hide Description The time to first biopsy confirmed new NMSC lesion starts at 1 day post randomization to biopsy and/or treatment of newly confirmed NMSC lesion.
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Median (95% Confidence Interval)
Unit of Measure: number of days
380 [1] 
(227 to NA)
163
(96 to 253)
[1]
Upper limit for 95% CI is not available because the curve representing the upper CI limit for the survivor function lies above 0.5 (or where the horizontal line at 50% does not intersect a CI), the upper CI limit for the median cannot be estimated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method Regression, Cox
Comments Stratified by baseline lesions
3.Secondary Outcome
Title Number of Lesion Free Subjects
Hide Description The overall number of subjects who were lesion free were compared between treatment groups with the Cochran Mantel Haenszel test stratified by baseline NMSC stratum. Within each stratum, the Fisher exact test was used to compare the proportions of lesion free subjects between treatment groups.
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: participants
17 9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
4.Secondary Outcome
Title Percentage of Patients With New Biopsy-confirmed NMSC: Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC)
Hide Description [Not Specified]
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: Percentage of Participants
SCC 67 69
BCC 33 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.799
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
5.Secondary Outcome
Title Grade Distribution of NMSC Lesions
Hide Description Number of subjects with at least 1 biopsy-confirmed new squamous cell carcinoma (SCC) or basal cell carcinoma (BCC).
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: participants
SCC Well differentiated 5 17
SCC Moderately differentiated 9 14
SCC Poorly differentiated 1 1
SCC Invasive 10 24
SCC In Situ 12 27
SCC Invasive with Perineural Invasion 2 1
SCC Invasive without Perineural Invasion 8 24
BCC Superficial 7 16
BCC Nodular 11 15
BCC Infiltrative 2 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments SCC Well differentiated
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments SCC Moderately differentiated
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.491
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments SCC Poorly differentiated
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.905
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments SCC Invasive
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments SCC In Situ
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments SCC Invasive with Perineural Invasion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.463
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments SCC Invasive without Perineural Invasion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments BCC Superficial
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.094
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments BCC Nodular
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.720
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments BCC Infiltrative
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.227
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
6.Secondary Outcome
Title Number of Recurrent NMSC Lesions Per Subject-year
Hide Description Recurrent NMSC lesions is defined as recurring at the site of a previously treated lesion.
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: lesions per participant year
0.107 0.134
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.748
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
7.Secondary Outcome
Title Subjects Reporting Incidence of Metastatic Disease Related to NMSC.
Hide Description The number of subjects with metastatic disease related to NMSC.
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: participants
1 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.425
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Stratified by baseline lesion strata
8.Secondary Outcome
Title Death Due to NMSC
Hide Description [Not Specified]
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: participants
0 0
9.Secondary Outcome
Title Number of Subjects Who Discontinue Assigned Therapy
Hide Description [Not Specified]
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: participants
31 23
10.Secondary Outcome
Title Nankivell-Calculated Glomerular Filtration Rate (GFR)
Hide Description GFR is an index of kidney function. GFR describes the flow rate of filtered fluid through the kidney. GFR can be measured directly or estimated using established formulas. For this study, GFR was calculated using Nankivell. A normal GFR is > 90 mL/min, although children and older people usually have a lower GFR. Lower values indicate poor kidney function. A GFR <15 is consistent with kidney failure.
Time Frame At 24 months (week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up. For the intention to treat analysis, a GFR of 0 was imputed for graft loss or death, and last observation carried forward (LOCF) for missing values.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Mean (Standard Deviation)
Unit of Measure: units on scale
72.49  (24.41) 68.42  (19.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.604
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
11.Secondary Outcome
Title Serum Creatinine Level
Hide Description Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatinine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. An increased level of creatinine in the blood indicates decreased kidney function. Normal adult blood levels of creatinine are 0.5 to 1.1 mg/dL for females and 0.6 to 1.2 mg/dL for males, however the normal values are age-dependent as elderly patients typically have smaller muscle mass.
Time Frame At 24 months (Week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up. All available data, no imputations.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 17 22
Mean (Standard Deviation)
Unit of Measure: μmol/L
139.35  (41.63) 135.23  (37.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.672
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title Number of Participants That Died
Hide Description [Not Specified]
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: participants
1 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
13.Secondary Outcome
Title Graft Survival Measured by Graft Loss
Hide Description Graft loss was defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 consecutive weeks), retransplant, or death.
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: graft loss
2 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.588
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
14.Secondary Outcome
Title Number of Subjects With Biopsy-Confirmed Acute Rejection
Hide Description [Not Specified]
Time Frame up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 39 47
Measure Type: Number
Unit of Measure: subjects
0 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.999
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
15.Secondary Outcome
Title Spot Urine Protein:Creatinine Ratio
Hide Description Subjects’ urine protein:creatinine ratios were summarized by each scheduled visit, and the nonparametric Wilcoxon rank sum test was used to compare the difference between groups.
Time Frame At 24 months (Week 104)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat: All randomly assigned subjects with at least 1 dose of study medication, includes data of subjects on therapy, those off therapy, and those who completed follow-up. Available data, no imputations.
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description:
All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted.
Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
Overall Number of Participants Analyzed 13 22
Median (Full Range)
Unit of Measure: ratio (mg/mg)
0.14
(0.09 to 1.07)
0.12
(0.04 to 0.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sirolimus (SRL) Based Regimen, Calcineurin Inhibitor (CNI) Based Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Hide Arm/Group Description All subjects discontinued Calcineurin inhibitors (CNI) after the morning dose on day 1. SRL was initiated with a loading dose of 6-12mg on day 1, followed by 2-4mg daily and was adjusted to maintain a whole blood trough concentration of 5-15ng/mL (high performance liquid chromatography [HPLC]). Once the SRL trough concentration was ≥ 5ng/mL, subjects receiving mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) at randomization had doses reduced to ≤1.5 g/day, ≤1080 mg/day or ≤75 mg/day respectively. If warranted subjects could be switched between MMF, MPS, or AZA or their doses decreased, temporarily withheld, or discontinued. Subjects receiving corticosteroids (CS) at time of randomization or if MMF, MPS, or AZA was discontinued, had to receive CS ≥2.5mg/day of prednisone. Subjects not receiving MMF, MPS, or AZA at time of randomization remained on a minimum of double therapy (SRL and CS). Addition of MMF, MPS, or AZA was permitted. Baseline CNI therapy was continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn. Cyclosporine could be switched to tacrolimus, and vice versa. If warranted subjects could be switched between MMF, MPS, or AZA or their doses could be decreased, temporarily withheld, or discontinued. Subjects undergoing discontinuation of MMF, MPS, or AZA had to receive CS ≥2.5 mg/day of prednisone or the equivalent thereof. If subjects were not receiving MMF, MPS, or AZA at the time of randomization, the addition of MMF, MPS, or AZA was permitted if clinically indicated. If subjects were receiving CS at the time of randomization, CS was maintained at ≥2.5 mg/day of prednisone or the equivalent thereof. CS withdrawal was prohibited. If subjects were not receiving CS at the time of randomization, treatment could be initiated during the conduct of the study if clinically indicated.
All-Cause Mortality
Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   15/39 (38.46%)   21/47 (44.68%) 
Blood and lymphatic system disorders     
Anemia *  1/39 (2.56%)  1/47 (2.13%) 
Lymphoma *  1/39 (2.56%)  0/47 (0.00%) 
Cardiac disorders     
Aneurysm *  0/39 (0.00%)  1/47 (2.13%) 
Angina pectoris *  1/39 (2.56%)  0/47 (0.00%) 
Arterial anomaly *  1/39 (2.56%)  0/47 (0.00%) 
Atrial fibrillation *  1/39 (2.56%)  0/47 (0.00%) 
Deep vein thrombosis *  0/39 (0.00%)  1/47 (2.13%) 
Heart failure *  1/39 (2.56%)  0/47 (0.00%) 
Hypertension *  1/39 (2.56%)  0/47 (0.00%) 
Left heart failure *  1/39 (2.56%)  0/47 (0.00%) 
Myocardial infarct *  1/39 (2.56%)  0/47 (0.00%) 
Thrombosis *  0/39 (0.00%)  1/47 (2.13%) 
Gastrointestinal disorders     
Colitis *  0/39 (0.00%)  1/47 (2.13%) 
Diarrhea *  1/39 (2.56%)  0/47 (0.00%) 
Gastroenteritis *  1/39 (2.56%)  3/47 (6.38%) 
Nausea and vomiting *  1/39 (2.56%)  0/47 (0.00%) 
Rectal hemorrhage *  0/39 (0.00%)  2/47 (4.26%) 
Vomiting *  1/39 (2.56%)  0/47 (0.00%) 
General disorders     
Allergic reaction *  1/39 (2.56%)  0/47 (0.00%) 
Cellulitis *  1/39 (2.56%)  1/47 (2.13%) 
Neoplasm *  0/39 (0.00%)  1/47 (2.13%) 
Sepsis *  0/39 (0.00%)  3/47 (6.38%) 
Transplant rejection *  1/39 (2.56%)  1/47 (2.13%) 
Metabolism and nutrition disorders     
Creatinine increased *  1/39 (2.56%)  0/47 (0.00%) 
Dehydration *  1/39 (2.56%)  0/47 (0.00%) 
Gout *  1/39 (2.56%)  0/47 (0.00%) 
Hyperkalemia *  1/39 (2.56%)  0/47 (0.00%) 
Subdural hematoma *  0/39 (0.00%)  1/47 (2.13%) 
Pleural effusion *  0/39 (0.00%)  1/47 (2.13%) 
Nervous system disorders     
Confusion *  0/39 (0.00%)  1/47 (2.13%) 
Encephalopathy *  0/39 (0.00%)  1/47 (2.13%) 
Renal and urinary disorders     
Acute kidney failure *  0/39 (0.00%)  1/47 (2.13%) 
Hematuria *  0/39 (0.00%)  1/47 (2.13%) 
Kidney failure *  1/39 (2.56%)  0/47 (0.00%) 
Prostatic carcinoma *  2/39 (5.13%)  1/47 (2.13%) 
Pyelonephritis *  0/39 (0.00%)  1/47 (2.13%) 
Urinary tract infection *  1/39 (2.56%)  2/47 (4.26%) 
Respiratory, thoracic and mediastinal disorders     
Bronchitis *  1/39 (2.56%)  0/47 (0.00%) 
Pharyngitis *  0/39 (0.00%)  1/47 (2.13%) 
Pneumonia *  3/39 (7.69%)  2/47 (4.26%) 
Pneumonitis *  3/39 (7.69%)  0/47 (0.00%) 
Respiratory failure *  0/39 (0.00%)  1/47 (2.13%) 
Sinusitis *  0/39 (0.00%)  1/47 (2.13%) 
Skin and subcutaneous tissue disorders     
Angioedema *  1/39 (2.56%)  0/47 (0.00%) 
Rash *  1/39 (2.56%)  0/47 (0.00%) 
Skin carcinoma *  1/39 (2.56%)  2/47 (4.26%) 
Skin melanoma *  0/39 (0.00%)  2/47 (4.26%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sirolimus (SRL) Based Regimen Calcineurin Inhibitor (CNI) Based Regimen
Affected / at Risk (%) Affected / at Risk (%)
Total   38/39 (97.44%)   40/47 (85.11%) 
Blood and lymphatic system disorders     
Anemia *  4/39 (10.26%)  2/47 (4.26%) 
Antinuclear antibody present *  1/39 (2.56%)  0/47 (0.00%) 
Ecchymosis *  2/39 (5.13%)  3/47 (6.38%) 
Leukocytosis *  0/39 (0.00%)  1/47 (2.13%) 
Leukopenia *  1/39 (2.56%)  0/47 (0.00%) 
Lymphocytosis *  0/39 (0.00%)  1/47 (2.13%) 
Neutropenia *  1/39 (2.56%)  0/47 (0.00%) 
Thrombocytopenia *  3/39 (7.69%)  0/47 (0.00%) 
Cardiac disorders     
Aneurysm *  0/39 (0.00%)  1/47 (2.13%) 
Angina pectoris *  1/39 (2.56%)  0/47 (0.00%) 
Arrhythmia *  0/39 (0.00%)  1/47 (2.13%) 
Arterial anomaly *  1/39 (2.56%)  0/47 (0.00%) 
Bradycardia *  0/39 (0.00%)  1/47 (2.13%) 
Cardiomegaly *  0/39 (0.00%)  1/47 (2.13%) 
Cardiovascular physical finding *  2/39 (5.13%)  1/47 (2.13%) 
Cyanosis *  0/39 (0.00%)  1/47 (2.13%) 
Deep vein thrombosis *  0/39 (0.00%)  1/47 (2.13%) 
Heart failure *  1/39 (2.56%)  0/47 (0.00%) 
Hemorrhage *  0/39 (0.00%)  1/47 (2.13%) 
Hypertension *  6/39 (15.38%)  4/47 (8.51%) 
Hypotension *  0/39 (0.00%)  3/47 (6.38%) 
Left heart failure *  1/39 (2.56%)  0/47 (0.00%) 
Myocardial infarct *  1/39 (2.56%)  0/47 (0.00%) 
Peripheral vascular disorder *  0/39 (0.00%)  1/47 (2.13%) 
Retinal artery occlusion *  0/39 (0.00%)  1/47 (2.13%) 
Tachycardia *  1/39 (2.56%)  1/47 (2.13%) 
Thrombophlebitis superficial *  0/39 (0.00%)  1/47 (2.13%) 
Thrombosis *  0/39 (0.00%)  1/47 (2.13%) 
Ear and labyrinth disorders     
Ear disorder *  0/39 (0.00%)  1/47 (2.13%) 
Ear pain *  1/39 (2.56%)  0/47 (0.00%) 
Otitis media *  0/39 (0.00%)  1/47 (2.13%) 
Endocrine disorders     
Thyroid disorder *  0/39 (0.00%)  1/47 (2.13%) 
Eye disorders     
Abnormal vision *  1/39 (2.56%)  0/47 (0.00%) 
Cataract specified *  2/39 (5.13%)  2/47 (4.26%) 
Conjunctivitis *  1/39 (2.56%)  0/47 (0.00%) 
Dry eyes *  1/39 (2.56%)  0/47 (0.00%) 
Eye disorder *  1/39 (2.56%)  1/47 (2.13%) 
Eye hemorrhage *  2/39 (5.13%)  0/47 (0.00%) 
Retinal disorder *  1/39 (2.56%)  0/47 (0.00%) 
Retinal edema *  1/39 (2.56%)  0/47 (0.00%) 
Gastrointestinal disorders     
Anorexia *  1/39 (2.56%)  0/47 (0.00%) 
Cholecystitis *  0/39 (0.00%)  1/47 (2.13%) 
Colitis *  0/39 (0.00%)  2/47 (4.26%) 
Constipation *  1/39 (2.56%)  2/47 (4.26%) 
Diarrhea *  16/39 (41.03%)  6/47 (12.77%) 
Duodenal ulcer *  0/39 (0.00%)  1/47 (2.13%) 
Dyspepsia *  1/39 (2.56%)  0/47 (0.00%) 
Fecal incontinence *  0/39 (0.00%)  1/47 (2.13%) 
Gastritis *  0/39 (0.00%)  2/47 (4.26%) 
Gastroenteritis *  0/39 (0.00%)  1/47 (2.13%) 
Gastroesophageal reflux disease *  1/39 (2.56%)  2/47 (4.26%) 
Gastrointestinal disorder *  0/39 (0.00%)  3/47 (6.38%) 
Liver fatty deposit *  0/39 (0.00%)  1/47 (2.13%) 
Liver function tests abnormal *  1/39 (2.56%)  1/47 (2.13%) 
Mouth ulceration *  13/39 (33.33%)  0/47 (0.00%) 
Nausea *  1/39 (2.56%)  2/47 (4.26%) 
Rectal disorder *  0/39 (0.00%)  1/47 (2.13%) 
Rectal hemorrhage *  2/39 (5.13%)  2/47 (4.26%) 
Stomatitis *  1/39 (2.56%)  0/47 (0.00%) 
Tongue discoloration *  1/39 (2.56%)  0/47 (0.00%) 
Vomiting *  2/39 (5.13%)  3/47 (6.38%) 
Taste perversion *  2/39 (5.13%)  0/47 (0.00%) 
General disorders     
Abdominal Pain *  1/39 (2.56%)  5/47 (10.64%) 
Accidental Injury *  4/39 (10.26%)  5/47 (10.64%) 
Adenoma *  0/39 (0.00%)  1/47 (2.13%) 
Allergic reaction *  3/39 (7.69%)  0/47 (0.00%) 
Asthenia *  2/39 (5.13%)  0/47 (0.00%) 
Back pain *  0/39 (0.00%)  2/47 (4.26%) 
Chest pain *  4/39 (10.26%)  2/47 (4.26%) 
Cyst *  1/39 (2.56%)  2/47 (4.26%) 
Drug level decreased *  0/39 (0.00%)  1/47 (2.13%) 
Drug level increased *  2/39 (5.13%)  0/47 (0.00%) 
Face edema *  1/39 (2.56%)  0/47 (0.00%) 
Fever *  1/39 (2.56%)  1/47 (2.13%) 
Flu syndrome *  1/39 (2.56%)  0/47 (0.00%) 
Headache *  5/39 (12.82%)  1/47 (2.13%) 
Hernia *  1/39 (2.56%)  0/47 (0.00%) 
Hormone level altered *  0/39 (0.00%)  1/47 (2.13%) 
Infection *  0/39 (0.00%)  1/47 (2.13%) 
Lab test abnormal *  2/39 (5.13%)  1/47 (2.13%) 
Malaise *  1/39 (2.56%)  0/47 (0.00%) 
Neck pain *  0/39 (0.00%)  1/47 (2.13%) 
Neoplasm *  0/39 (0.00%)  2/47 (4.26%) 
Pain *  6/39 (15.38%)  5/47 (10.64%) 
Pelvic pain *  1/39 (2.56%)  3/47 (6.38%) 
Tolerance decreased *  2/39 (5.13%)  0/47 (0.00%) 
Transplant rejection *  0/39 (0.00%)  1/47 (2.13%) 
Allergic reaction other than drug *  0/39 (0.00%)  1/47 (2.13%) 
Device malfunction *  1/39 (2.56%)  0/47 (0.00%) 
Local reaction to procedure *  0/39 (0.00%)  1/47 (2.13%) 
Metabolism and nutrition disorders     
Avitaminosis *  0/39 (0.00%)  1/47 (2.13%) 
Creatinine increased *  2/39 (5.13%)  4/47 (8.51%) 
Dehydration *  1/39 (2.56%)  0/47 (0.00%) 
Edema *  1/39 (2.56%)  0/47 (0.00%) 
Glucose tolerance decreased *  0/39 (0.00%)  1/47 (2.13%) 
Gout *  5/39 (12.82%)  3/47 (6.38%) 
Hypercholesteremia *  3/39 (7.69%)  2/47 (4.26%) 
Hyperglycemia *  2/39 (5.13%)  2/47 (4.26%) 
Hyperkalemia *  2/39 (5.13%)  0/47 (0.00%) 
Hyperlipemia *  5/39 (12.82%)  2/47 (4.26%) 
Hypoglycemia *  0/39 (0.00%)  1/47 (2.13%) 
Hypokalemia *  2/39 (5.13%)  0/47 (0.00%) 
Hypomagnesemia *  1/39 (2.56%)  1/47 (2.13%) 
Hypophosphatemia *  0/39 (0.00%)  1/47 (2.13%) 
Lactic dehydrogenase increased *  0/39 (0.00%)  1/47 (2.13%) 
Peripheral edema *  16/39 (41.03%)  3/47 (6.38%) 
Sgpt increased *  0/39 (0.00%)  1/47 (2.13%) 
Thirst *  1/39 (2.56%)  0/47 (0.00%) 
Weight loss *  0/39 (0.00%)  2/47 (4.26%) 
Musculoskeletal and connective tissue disorders     
Arthralgia *  5/39 (12.82%)  6/47 (12.77%) 
Arthritis *  0/39 (0.00%)  1/47 (2.13%) 
Arthrosis *  1/39 (2.56%)  1/47 (2.13%) 
Bone disorder *  0/39 (0.00%)  1/47 (2.13%) 
Joint disorder *  1/39 (2.56%)  1/47 (2.13%) 
Myalgia *  1/39 (2.56%)  0/47 (0.00%) 
Myopathy *  0/39 (0.00%)  1/47 (2.13%) 
Osteopenia *  2/39 (5.13%)  1/47 (2.13%) 
Plantar fasciitis *  0/39 (0.00%)  1/47 (2.13%) 
Synovitis *  1/39 (2.56%)  0/47 (0.00%) 
Nervous system disorders     
Depression *  1/39 (2.56%)  1/47 (2.13%) 
Dizziness *  1/39 (2.56%)  3/47 (6.38%) 
Dizziness postural *  0/39 (0.00%)  2/47 (4.26%) 
Emotional lability *  1/39 (2.56%)  0/47 (0.00%) 
Hypesthesia *  0/39 (0.00%)  1/47 (2.13%) 
Insomnia *  1/39 (2.56%)  0/47 (0.00%) 
Nervousness *  1/39 (2.56%)  0/47 (0.00%) 
Neuropathy *  0/39 (0.00%)  1/47 (2.13%) 
Paresthesia *  2/39 (5.13%)  0/47 (0.00%) 
Sleep disorder *  1/39 (2.56%)  0/47 (0.00%) 
Somnolence *  2/39 (5.13%)  1/47 (2.13%) 
Subdural hematoma *  0/39 (0.00%)  1/47 (2.13%) 
Renal and urinary disorders     
Acute kidney failure *  1/39 (2.56%)  1/47 (2.13%) 
Albuminuria *  7/39 (17.95%)  0/47 (0.00%) 
Hematuria *  1/39 (2.56%)  3/47 (6.38%) 
Hydronephrosis *  1/39 (2.56%)  1/47 (2.13%) 
Hydroureter *  1/39 (2.56%)  0/47 (0.00%) 
Kidney function abnormal *  0/39 (0.00%)  1/47 (2.13%) 
Prostatic specific antigen increase *  0/39 (0.00%)  1/47 (2.13%) 
Testis disorder *  1/39 (2.56%)  1/47 (2.13%) 
Urinary incontinence *  0/39 (0.00%)  1/47 (2.13%) 
Urinary retention *  1/39 (2.56%)  0/47 (0.00%) 
Urogenital disorder *  1/39 (2.56%)  0/47 (0.00%) 
Reproductive system and breast disorders     
Breast disorder *  1/39 (2.56%)  0/47 (0.00%) 
Breast pain *  0/39 (0.00%)  1/47 (2.13%) 
Respiratory, thoracic and mediastinal disorders     
Atelectasis *  0/39 (0.00%)  1/47 (2.13%) 
Bronchitis *  0/39 (0.00%)  1/47 (2.13%) 
Cough increased *  8/39 (20.51%)  6/47 (12.77%) 
Dyspnea *  4/39 (10.26%)  2/47 (4.26%) 
Epistaxis *  4/39 (10.26%)  0/47 (0.00%) 
Hypoxia *  0/39 (0.00%)  1/47 (2.13%) 
Laryngitis *  0/39 (0.00%)  1/47 (2.13%) 
Lung infiltration nos *  1/39 (2.56%)  0/47 (0.00%) 
Pharyngitis *  2/39 (5.13%)  1/47 (2.13%) 
Pleural effusion *  0/39 (0.00%)  1/47 (2.13%) 
Pneumonia *  0/39 (0.00%)  1/47 (2.13%) 
Pneumonitis *  6/39 (15.38%)  0/47 (0.00%) 
Respiratory distress syndrome *  0/39 (0.00%)  1/47 (2.13%) 
Rhinitis *  2/39 (5.13%)  0/47 (0.00%) 
Wheezing *  1/39 (2.56%)  0/47 (0.00%) 
Skin and subcutaneous tissue disorders     
Acne *  7/39 (17.95%)  1/47 (2.13%) 
Angioedema *  2/39 (5.13%)  0/47 (0.00%) 
Dry skin *  2/39 (5.13%)  0/47 (0.00%) 
Eczema *  3/39 (7.69%)  0/47 (0.00%) 
Folliculitis *  3/39 (7.69%)  1/47 (2.13%) 
Fungal dermatitis *  0/39 (0.00%)  1/47 (2.13%) 
Herpes simplex *  1/39 (2.56%)  1/47 (2.13%) 
Herpes zoster *  1/39 (2.56%)  1/47 (2.13%) 
Maculopapular rash *  1/39 (2.56%)  0/47 (0.00%) 
Pruritic rash *  3/39 (7.69%)  0/47 (0.00%) 
Pruritus *  1/39 (2.56%)  0/47 (0.00%) 
Pustular rash *  0/39 (0.00%)  1/47 (2.13%) 
Rash *  13/39 (33.33%)  1/47 (2.13%) 
Seborrheic keratosis *  0/39 (0.00%)  1/47 (2.13%) 
Skin carcinoma *  1/39 (2.56%)  1/47 (2.13%) 
Skin disorder *  1/39 (2.56%)  3/47 (6.38%) 
Skin hypertrophy *  2/39 (5.13%)  4/47 (8.51%) 
Subcutaneous emphysema *  0/39 (0.00%)  1/47 (2.13%) 
Urticaria *  1/39 (2.56%)  0/47 (0.00%) 
*
Indicates events were collected by non-systematic assessment
A blinded review of data in May 2007 determined there was minimal added power in follow-up through 2 years vs. 1 year. The study was then amended to require at least 1 year of follow-up instead of 2 years.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
Results Point of Contact
Name/Title: U. S. Contact Center
Organization: Wyeth
Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier: NCT00129961     History of Changes
Other Study ID Numbers: 0468H1-407
First Submitted: August 1, 2005
First Posted: August 12, 2005
Results First Submitted: January 29, 2010
Results First Posted: March 23, 2012
Last Update Posted: April 11, 2012