Trial Outcomes & Findings for Study Evaluating the Effect of Sirolimus on Non-Melanoma Skin Cancer in Kidney Transplant Recipients (NCT NCT00129961)
NCT ID: NCT00129961
Last Updated: 2012-04-11
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
86 participants
Primary outcome timeframe
up to 24 months
Results posted on
2012-04-11
Participant Flow
Subjects were recruited in Australia, New Zealand and North America from August 2005 (first subject randomized September 2005) through October 2007.
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).
Participant milestones
| Measure |
Sirolimus (SRL) Based Regimen
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
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continued after randomization and doses could be adjusted throughout the study as indicated, but therapy could not be withdrawn.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 Study
STARTED
|
39
|
47
|
|
Overall Study
COMPLETED
|
20
|
24
|
|
Overall Study
NOT COMPLETED
|
19
|
23
|
Reasons for withdrawal
| Measure |
Sirolimus (SRL) Based Regimen
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
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 Study
Adverse Event
|
1
|
0
|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Withdrawal by Sponsor
|
14
|
20
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Missing Record
|
0
|
1
|
Baseline Characteristics
Study Evaluating the Effect of Sirolimus on Non-Melanoma Skin Cancer in Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
59.08 years
n=5 Participants
|
58.98 years
n=7 Participants
|
59.02 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
|
Stratification Group
0-5 Lesions in 12 months prior
|
33 subjects
n=5 Participants
|
39 subjects
n=7 Participants
|
72 subjects
n=5 Participants
|
|
Stratification Group
6-20 Lesions in 12 months prior
|
6 subjects
n=5 Participants
|
8 subjects
n=7 Participants
|
14 subjects
n=5 Participants
|
|
Time from Current Transplantation to Randomization
|
114.98 Months
STANDARD_DEVIATION 57.63 • n=5 Participants
|
109.57 Months
STANDARD_DEVIATION 55.08 • n=7 Participants
|
112.02 Months
STANDARD_DEVIATION 55.98 • n=5 Participants
|
PRIMARY outcome
Timeframe: up to 24 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
New Biopsy-Confirmed Nonmelanoma Skin Cancer (NMSC) Lesions Per Subject Per Year
|
1.31 Standardized Yearly Rate of NMSC
0.52
|
2.48 Standardized Yearly Rate of NMSC
0.69
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Time to First Biopsy Confirmed New NMSC Lesion.
|
380 number of days
95% Confidence Interval 42.42 • Interval 227.0 to
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.
|
163 number of days
95% Confidence Interval 42.32 • Interval 96.0 to 253.0
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Number of Lesion Free Subjects
|
17 participants
|
9 participants
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Percentage of Patients With New Biopsy-confirmed NMSC: Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC)
SCC
|
67 Percentage of Participants
|
69 Percentage of Participants
|
|
Percentage of Patients With New Biopsy-confirmed NMSC: Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC)
BCC
|
33 Percentage of Participants
|
31 Percentage of Participants
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Number of subjects with at least 1 biopsy-confirmed new squamous cell carcinoma (SCC) or basal cell carcinoma (BCC).
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Grade Distribution of NMSC Lesions
SCC Well differentiated
|
5 participants
|
17 participants
|
|
Grade Distribution of NMSC Lesions
SCC Moderately differentiated
|
9 participants
|
14 participants
|
|
Grade Distribution of NMSC Lesions
SCC Poorly differentiated
|
1 participants
|
1 participants
|
|
Grade Distribution of NMSC Lesions
SCC Invasive
|
10 participants
|
24 participants
|
|
Grade Distribution of NMSC Lesions
SCC In Situ
|
12 participants
|
27 participants
|
|
Grade Distribution of NMSC Lesions
SCC Invasive with Perineural Invasion
|
2 participants
|
1 participants
|
|
Grade Distribution of NMSC Lesions
SCC Invasive without Perineural Invasion
|
8 participants
|
24 participants
|
|
Grade Distribution of NMSC Lesions
BCC Superficial
|
7 participants
|
16 participants
|
|
Grade Distribution of NMSC Lesions
BCC Nodular
|
11 participants
|
15 participants
|
|
Grade Distribution of NMSC Lesions
BCC Infiltrative
|
2 participants
|
6 participants
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Recurrent NMSC lesions is defined as recurring at the site of a previously treated lesion.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Number of Recurrent NMSC Lesions Per Subject-year
|
0.107 lesions per participant year
0.09
|
0.134 lesions per participant year
0.10
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
The number of subjects with metastatic disease related to NMSC.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Subjects Reporting Incidence of Metastatic Disease Related to NMSC.
|
1 participants
|
3 participants
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Death Due to NMSC
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Number of Subjects Who Discontinue Assigned Therapy
|
31 participants
|
23 participants
|
SECONDARY outcome
Timeframe: At 24 months (week 104)Population: 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.
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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Nankivell-Calculated Glomerular Filtration Rate (GFR)
|
72.49 units on scale
Standard Deviation 24.41
|
68.42 units on scale
Standard Deviation 19.91
|
SECONDARY outcome
Timeframe: At 24 months (Week 104)Population: 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.
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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=17 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=22 Participants
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.
|
|---|---|---|
|
Serum Creatinine Level
|
139.35 μmol/L
Standard Deviation 41.63
|
135.23 μmol/L
Standard Deviation 37.84
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Number of Participants That Died
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Graft loss was defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for \>8 consecutive weeks), retransplant, or death.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Graft Survival Measured by Graft Loss
|
2 graft loss
|
1 graft loss
|
SECONDARY outcome
Timeframe: up to 24 monthsPopulation: 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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=39 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 Participants
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.
|
|---|---|---|
|
Number of Subjects With Biopsy-Confirmed Acute Rejection
|
0 subjects
|
1 subjects
|
SECONDARY outcome
Timeframe: At 24 months (Week 104)Population: 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.
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.
Outcome measures
| Measure |
Sirolimus (SRL) Based Regimen
n=13 Participants
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=22 Participants
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.
|
|---|---|---|
|
Spot Urine Protein:Creatinine Ratio
|
0.14 ratio (mg/mg)
Full Range 0.28 • Interval 0.09 to 1.07
|
0.12 ratio (mg/mg)
Full Range 0.08 • Interval 0.04 to 0.34
|
Adverse Events
Sirolimus (SRL) Based Regimen
Serious events: 15 serious events
Other events: 38 other events
Deaths: 0 deaths
Calcineurin Inhibitor (CNI) Based Regimen
Serious events: 21 serious events
Other events: 40 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sirolimus (SRL) Based Regimen
n=39 participants at risk
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 participants at risk
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.
|
|---|---|---|
|
General disorders
Allergic reaction
|
2.6%
1/39
|
0.00%
0/47
|
|
General disorders
Cellulitis
|
2.6%
1/39
|
2.1%
1/47
|
|
General disorders
Neoplasm
|
0.00%
0/39
|
2.1%
1/47
|
|
General disorders
Sepsis
|
0.00%
0/39
|
6.4%
3/47
|
|
General disorders
Transplant rejection
|
2.6%
1/39
|
2.1%
1/47
|
|
Cardiac disorders
Aneurysm
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Angina pectoris
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Arterial anomaly
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Atrial fibrillation
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Deep vein thrombosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Heart failure
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Hypertension
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Left heart failure
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Myocardial infarct
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Thrombosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Diarrhea
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Gastroenteritis
|
2.6%
1/39
|
6.4%
3/47
|
|
Gastrointestinal disorders
Nausea and vomiting
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
0.00%
0/39
|
4.3%
2/47
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
1/39
|
0.00%
0/47
|
|
Blood and lymphatic system disorders
Anemia
|
2.6%
1/39
|
2.1%
1/47
|
|
Blood and lymphatic system disorders
Lymphoma
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Creatinine increased
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Dehydration
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Gout
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
2.6%
1/39
|
0.00%
0/47
|
|
Nervous system disorders
Confusion
|
0.00%
0/39
|
2.1%
1/47
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Subdural hematoma
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
2.6%
1/39
|
0.00%
0/47
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Pleural effusion
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
7.7%
3/39
|
4.3%
2/47
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
7.7%
3/39
|
0.00%
0/47
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
2.6%
1/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.6%
1/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Skin carcinoma
|
2.6%
1/39
|
4.3%
2/47
|
|
Skin and subcutaneous tissue disorders
Skin melanoma
|
0.00%
0/39
|
4.3%
2/47
|
|
Renal and urinary disorders
Acute kidney failure
|
0.00%
0/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Kidney failure
|
2.6%
1/39
|
0.00%
0/47
|
|
Renal and urinary disorders
Prostatic carcinoma
|
5.1%
2/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Pyelonephritis
|
0.00%
0/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Urinary tract infection
|
2.6%
1/39
|
4.3%
2/47
|
Other adverse events
| Measure |
Sirolimus (SRL) Based Regimen
n=39 participants at risk
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.
|
Calcineurin Inhibitor (CNI) Based Regimen
n=47 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Antinuclear antibody present
|
2.6%
1/39
|
0.00%
0/47
|
|
Blood and lymphatic system disorders
Lymphocytosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.6%
1/39
|
0.00%
0/47
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
7.7%
3/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Avitaminosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Blood and lymphatic system disorders
Ecchymosis
|
5.1%
2/39
|
6.4%
3/47
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Gout
|
12.8%
5/39
|
6.4%
3/47
|
|
Metabolism and nutrition disorders
Hypercholesteremia
|
7.7%
3/39
|
4.3%
2/47
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.1%
2/39
|
4.3%
2/47
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
5.1%
2/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Hyperlipemia
|
12.8%
5/39
|
4.3%
2/47
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Creatinine increased
|
5.1%
2/39
|
8.5%
4/47
|
|
Metabolism and nutrition disorders
Dehydration
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Edema
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Glucose tolerance decreased
|
0.00%
0/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Hypokalemia
|
5.1%
2/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
2.6%
1/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Lactic dehydrogenase increased
|
0.00%
0/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Peripheral edema
|
41.0%
16/39
|
6.4%
3/47
|
|
Metabolism and nutrition disorders
Sgpt increased
|
0.00%
0/39
|
2.1%
1/47
|
|
Metabolism and nutrition disorders
Thirst
|
2.6%
1/39
|
0.00%
0/47
|
|
Metabolism and nutrition disorders
Weight loss
|
0.00%
0/39
|
4.3%
2/47
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.8%
5/39
|
12.8%
6/47
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/39
|
2.1%
1/47
|
|
Musculoskeletal and connective tissue disorders
Arthrosis
|
2.6%
1/39
|
2.1%
1/47
|
|
Musculoskeletal and connective tissue disorders
Bone disorder
|
0.00%
0/39
|
2.1%
1/47
|
|
Musculoskeletal and connective tissue disorders
Joint disorder
|
2.6%
1/39
|
2.1%
1/47
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.6%
1/39
|
0.00%
0/47
|
|
Musculoskeletal and connective tissue disorders
Myopathy
|
0.00%
0/39
|
2.1%
1/47
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
5.1%
2/39
|
2.1%
1/47
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Musculoskeletal and connective tissue disorders
Synovitis
|
2.6%
1/39
|
0.00%
0/47
|
|
Nervous system disorders
Depression
|
2.6%
1/39
|
2.1%
1/47
|
|
Nervous system disorders
Dizziness
|
2.6%
1/39
|
6.4%
3/47
|
|
Nervous system disorders
Dizziness postural
|
0.00%
0/39
|
4.3%
2/47
|
|
Nervous system disorders
Emotional lability
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Constipation
|
2.6%
1/39
|
4.3%
2/47
|
|
Gastrointestinal disorders
Diarrhea
|
41.0%
16/39
|
12.8%
6/47
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Dyspepsia
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Fecal incontinence
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/39
|
4.3%
2/47
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
2.6%
1/39
|
4.3%
2/47
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/39
|
6.4%
3/47
|
|
Gastrointestinal disorders
Liver fatty deposit
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Liver function tests abnormal
|
2.6%
1/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Mouth ulceration
|
33.3%
13/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Nausea
|
2.6%
1/39
|
4.3%
2/47
|
|
Gastrointestinal disorders
Rectal disorder
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
5.1%
2/39
|
4.3%
2/47
|
|
Gastrointestinal disorders
Stomatitis
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Tongue discoloration
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
2/39
|
6.4%
3/47
|
|
Endocrine disorders
Thyroid disorder
|
0.00%
0/39
|
2.1%
1/47
|
|
Blood and lymphatic system disorders
Anemia
|
10.3%
4/39
|
4.3%
2/47
|
|
General disorders
Abdominal Pain
|
2.6%
1/39
|
10.6%
5/47
|
|
General disorders
Accidental Injury
|
10.3%
4/39
|
10.6%
5/47
|
|
General disorders
Adenoma
|
0.00%
0/39
|
2.1%
1/47
|
|
General disorders
Allergic reaction
|
7.7%
3/39
|
0.00%
0/47
|
|
General disorders
Asthenia
|
5.1%
2/39
|
0.00%
0/47
|
|
General disorders
Back pain
|
0.00%
0/39
|
4.3%
2/47
|
|
General disorders
Chest pain
|
10.3%
4/39
|
4.3%
2/47
|
|
General disorders
Cyst
|
2.6%
1/39
|
4.3%
2/47
|
|
General disorders
Drug level decreased
|
0.00%
0/39
|
2.1%
1/47
|
|
General disorders
Drug level increased
|
5.1%
2/39
|
0.00%
0/47
|
|
General disorders
Face edema
|
2.6%
1/39
|
0.00%
0/47
|
|
General disorders
Fever
|
2.6%
1/39
|
2.1%
1/47
|
|
General disorders
Flu syndrome
|
2.6%
1/39
|
0.00%
0/47
|
|
General disorders
Headache
|
12.8%
5/39
|
2.1%
1/47
|
|
General disorders
Hernia
|
2.6%
1/39
|
0.00%
0/47
|
|
General disorders
Hormone level altered
|
0.00%
0/39
|
2.1%
1/47
|
|
General disorders
Infection
|
0.00%
0/39
|
2.1%
1/47
|
|
General disorders
Lab test abnormal
|
5.1%
2/39
|
2.1%
1/47
|
|
General disorders
Malaise
|
2.6%
1/39
|
0.00%
0/47
|
|
General disorders
Neck pain
|
0.00%
0/39
|
2.1%
1/47
|
|
General disorders
Neoplasm
|
0.00%
0/39
|
4.3%
2/47
|
|
General disorders
Pain
|
15.4%
6/39
|
10.6%
5/47
|
|
General disorders
Pelvic pain
|
2.6%
1/39
|
6.4%
3/47
|
|
General disorders
Tolerance decreased
|
5.1%
2/39
|
0.00%
0/47
|
|
General disorders
Transplant rejection
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Aneurysm
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Angina pectoris
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Arterial anomaly
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Cardiomegaly
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Cardiovascular physical finding
|
5.1%
2/39
|
2.1%
1/47
|
|
Cardiac disorders
Cyanosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Deep vein thrombosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Heart failure
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Hemorrhage
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Hypertension
|
15.4%
6/39
|
8.5%
4/47
|
|
Cardiac disorders
Hypotension
|
0.00%
0/39
|
6.4%
3/47
|
|
Cardiac disorders
Left heart failure
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Myocardial infarct
|
2.6%
1/39
|
0.00%
0/47
|
|
Cardiac disorders
Peripheral vascular disorder
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Retinal artery occlusion
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Tachycardia
|
2.6%
1/39
|
2.1%
1/47
|
|
Cardiac disorders
Thrombophlebitis superficial
|
0.00%
0/39
|
2.1%
1/47
|
|
Cardiac disorders
Thrombosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Anorexia
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Cholecystitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/39
|
4.3%
2/47
|
|
Nervous system disorders
Hypesthesia
|
0.00%
0/39
|
2.1%
1/47
|
|
Nervous system disorders
Insomnia
|
2.6%
1/39
|
0.00%
0/47
|
|
Nervous system disorders
Nervousness
|
2.6%
1/39
|
0.00%
0/47
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/39
|
2.1%
1/47
|
|
Nervous system disorders
Paresthesia
|
5.1%
2/39
|
0.00%
0/47
|
|
Nervous system disorders
Sleep disorder
|
2.6%
1/39
|
0.00%
0/47
|
|
Nervous system disorders
Somnolence
|
5.1%
2/39
|
2.1%
1/47
|
|
Nervous system disorders
Subdural hematoma
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Cough increased
|
20.5%
8/39
|
12.8%
6/47
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
10.3%
4/39
|
4.3%
2/47
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.3%
4/39
|
0.00%
0/47
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Laryngitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration nos
|
2.6%
1/39
|
0.00%
0/47
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
5.1%
2/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
15.4%
6/39
|
0.00%
0/47
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress syndrome
|
0.00%
0/39
|
2.1%
1/47
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
5.1%
2/39
|
0.00%
0/47
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
2.6%
1/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Acne
|
17.9%
7/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
5.1%
2/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.1%
2/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Eczema
|
7.7%
3/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Folliculitis
|
7.7%
3/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Fungal dermatitis
|
0.00%
0/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Herpes simplex
|
2.6%
1/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Herpes zoster
|
2.6%
1/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
2.6%
1/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Pruritic rash
|
7.7%
3/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.6%
1/39
|
0.00%
0/47
|
|
Skin and subcutaneous tissue disorders
Pustular rash
|
0.00%
0/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
13/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Seborrheic keratosis
|
0.00%
0/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Skin carcinoma
|
2.6%
1/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
2.6%
1/39
|
6.4%
3/47
|
|
Skin and subcutaneous tissue disorders
Skin hypertrophy
|
5.1%
2/39
|
8.5%
4/47
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
0.00%
0/39
|
2.1%
1/47
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
2.6%
1/39
|
0.00%
0/47
|
|
Eye disorders
Abnormal vision
|
2.6%
1/39
|
0.00%
0/47
|
|
Eye disorders
Cataract specified
|
5.1%
2/39
|
4.3%
2/47
|
|
Eye disorders
Conjunctivitis
|
2.6%
1/39
|
0.00%
0/47
|
|
Eye disorders
Dry eyes
|
2.6%
1/39
|
0.00%
0/47
|
|
Ear and labyrinth disorders
Ear disorder
|
0.00%
0/39
|
2.1%
1/47
|
|
Ear and labyrinth disorders
Ear pain
|
2.6%
1/39
|
0.00%
0/47
|
|
Eye disorders
Eye disorder
|
2.6%
1/39
|
2.1%
1/47
|
|
Eye disorders
Eye hemorrhage
|
5.1%
2/39
|
0.00%
0/47
|
|
Ear and labyrinth disorders
Otitis media
|
0.00%
0/39
|
2.1%
1/47
|
|
Eye disorders
Retinal disorder
|
2.6%
1/39
|
0.00%
0/47
|
|
Eye disorders
Retinal edema
|
2.6%
1/39
|
0.00%
0/47
|
|
Gastrointestinal disorders
Taste perversion
|
5.1%
2/39
|
0.00%
0/47
|
|
Renal and urinary disorders
Acute kidney failure
|
2.6%
1/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Albuminuria
|
17.9%
7/39
|
0.00%
0/47
|
|
Reproductive system and breast disorders
Breast disorder
|
2.6%
1/39
|
0.00%
0/47
|
|
Reproductive system and breast disorders
Breast pain
|
0.00%
0/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Hematuria
|
2.6%
1/39
|
6.4%
3/47
|
|
Renal and urinary disorders
Hydronephrosis
|
2.6%
1/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Hydroureter
|
2.6%
1/39
|
0.00%
0/47
|
|
Renal and urinary disorders
Kidney function abnormal
|
0.00%
0/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Prostatic specific antigen increase
|
0.00%
0/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Testis disorder
|
2.6%
1/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/39
|
2.1%
1/47
|
|
Renal and urinary disorders
Urinary retention
|
2.6%
1/39
|
0.00%
0/47
|
|
Renal and urinary disorders
Urogenital disorder
|
2.6%
1/39
|
0.00%
0/47
|
|
General disorders
Allergic reaction other than drug
|
0.00%
0/39
|
2.1%
1/47
|
|
General disorders
Device malfunction
|
2.6%
1/39
|
0.00%
0/47
|
|
General disorders
Local reaction to procedure
|
0.00%
0/39
|
2.1%
1/47
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER