Study Evaluating of Calcineurin Inhibitors Versus Sirolimus in Renal Allograft Recipient

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00452361
• Collaborator: (none)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

This study will evaluate whether conversion from cyclosporine, a calcineurin inhibitor (CI) to sirolimus (SRL) results in improved long-term renal function without a negative impact on safety or immunosuppressive efficacy, and to further examine the potential of SRL to reduce the severity and/or progression of chronic allograft nephropathy (CAN).

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: Sirolimus+MMF or MPS or AZA+Steroid; Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid	Phase 4

Detailed Description

This open-label, randomized, parallel-group, comparative, outpatient study will be conducted in multiple centers in Taiwan.

The study will randomize approximately 120 patients. 80 patients will be randomized to the SRL therapy group (conversion from CI- to SRL-based immunosuppression: group A) and 40 patients to the CI therapy group (continued CI therapy: group B).

Dosage and Administration

SRL Therapy: At the time of randomization on day 1, each patient will have been receiving:

• triple therapy with a CI (tacrolimus or CsA) that began at the time of transplantation or within 2 weeks thereafter AND

• corticosteroids corresponding to a dosage range of 2.5 to 15 mg/day for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent for at least 12 weeks before randomization, PLUS

• either MMF (minimum dose 500 mg/day)/MPS (minimum dose 360 mg/day) or AZA (minimum dose 50 mg/day) for at least 12 weeks before randomization.

SRL will be added to the immunosuppressive regimen for Group A. Group B will continue on this CI immunosuppressive regimen.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Comparative Evaluation of Conversion From Calcineurin Inhibitors to Sirolimus Versus Continued Use of Calcineurin Inhibitors in Renal Allograft Recipient
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Sirolimus therapy	Drug: Sirolimus+MMF or MPS or AZA+Steroid; Corticosteroids will be administered according to local practice, within a daily maintenance dosage range of 2.5 to15 mg for prednisone or prednisolone (2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.
Active Comparator: 2 Calcineurin Inhibitor therapy (either cyclosporine or tacrolimus)	Drug: Calcineurin Inhibitors (either cyclosporine or tacrolimus)+MMF or MPS or AZA+Steroid; The maintenance dose of: MMF will not exceed 1500 mg/day or PMS will not exceed 1080 mg/day AZA will not exceed 75 mg/day Thereafter, at the discretion of the investigator, MMF/MPS or AZA may be: continued for the entire 104-week period of randomized therapy subsequently discontinued restarted after discontinuation

Outcome Measures

Primary Outcome Measures

1. Change in Glomerular Filtration Rate (GFR) Change From Baseline [104 weeks]

   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. GFR was calculated using Nankivell formula. 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.

Secondary Outcome Measures

1. Change in Glomerular Filtration Rate (GFR) [Baseline and Week 24]

   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. GFR was calculated using Nankivell formula. 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.

2. Change in Glomerular Filtration Rate (GFR) [Baseline and Week 52]

   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. GFR was calculated using Nankivell formula. 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.

3. Change in Glomerular Filtration Rate (GFR) [Baseline and Week 104]

   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. GFR was calculated using Nankivell formula. 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.

4. Patient and Graft Survival [Week 24]

   Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.

5. Patient and Graft Survival [Week 52]

   Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.

6. Patient and Graft Survival [Week 104]

   Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.

7. Change From Baseline in Diastolic Blood Pressure at Week 24 [Baseline and Week 24]

   Value at Week 24 minus value at baseline.

8. Change From Baseline in Diastolic Blood Pressure at Week 52 [Baseline and Week 52]

   Value at Week 52 minus value at baseline.

9. Change From Baseline in Diastolic Blood Pressure at Week 104 [Baseline and Week 104]

   Value at Week 104 minus value at baseline.

10. Change From Baseline in Systolic Blood Pressure at Week 24 [Baseline and Week 24]

    Value at Week 24 minus value at baseline.

11. Change From Baseline in Systolic Blood Pressure at Week 52 [Baseline and Week 52]

    Value at Week 52 minus value at baseline.

12. Change From Baseline in Systolic Blood Pressure at Week 104 [Baseline and Week 104]

    Value at Week 104 minus value at baseline.

13. Change From Baseline in the Severity and Progression of Biopsy-Confirmed Chronic Allograft Nephropathy (CAN) at Week 104 [Baseline and Week 104]

14. Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52 [Weeks 52]

15. Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104 [Week 104]

16. Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24 [Week 24]

17. Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52 [Week 52]

18. Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104 [Week 104]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must be at least 18 years of age.

• Subjects who are 6 to 60 months after renal transplantation.

• Subjects who have a stable graft function.

Exclusion Criteria:

• Subjects with active major infection, including HIV, decreased platelets, elevated lipids, or multiple organ transplants.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Select Cities		Taiwan

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Medical Monitor, Wyeth is now a wholly owned subsidiary of Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
• ClinicalTrials.gov Identifier: NCT00452361
• Other Study ID Numbers: 0468H-101864
• First Posted: Mar 27, 2007
• Last Update Posted: Sep 3, 2012
• Last Verified: Jul 1, 2012

• Additional relevant MeSH terms: Cyclosporine; Sirolimus; Tacrolimus; Cyclosporins; Calcineurin Inhibitors

Study Results

Participant Flow

Recruitment Details	Patients were recruited in Taiwan from April 2007 to May 2008.
Pre-assignment Detail	After consent and eligibility criteria patients needed to be receiving: triple therapy with a Calcineurin Inhibitor (CI) (tacrolimus or cyclosporine) that began at the time of transplantation or ≤2 weeks thereafter and corticosteroids plus either mycophenolate mofetil (MMF)/mycophenolate sodium (MPS) or azathioprine (AZA) for at least 12 weeks.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Period Title: Overall Study
STARTED	21	10
COMPLETED	0	0
NOT COMPLETED	21	10

Baseline Characteristics

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)	Total
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.	Total of all reporting groups
Overall Participants	21	10	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.8 (7.9)	42.2 (13.9)	43.3 (10.2)
Sex: Female, Male (Count of Participants)
Female	11 52.4%	2 20%	13 41.9%
Male	10 47.6%	8 80%	18 58.1%

Outcome Measures

1. Primary Outcome

Title	Change in Glomerular Filtration Rate (GFR) Change From Baseline
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. GFR was calculated using Nankivell formula. 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	104 weeks

Outcome Measure Data

Analysis Population Description

No patients completed 104 weeks and therefore no data were available for efficacy analysis.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

2. Secondary Outcome

Title	Change in Glomerular Filtration Rate (GFR)
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. GFR was calculated using Nankivell formula. 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	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

3. Secondary Outcome

Title	Change in Glomerular Filtration Rate (GFR)
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. GFR was calculated using Nankivell formula. 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	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

4. Secondary Outcome

Title	Change in Glomerular Filtration Rate (GFR)
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. GFR was calculated using Nankivell formula. 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	Baseline and Week 104

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

5. Secondary Outcome

Title	Patient and Graft Survival
Description	Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

6. Secondary Outcome

Title	Patient and Graft Survival
Description	Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

7. Secondary Outcome

Title	Patient and Graft Survival
Description	Patient survival defined as participants living with or without a functioning graft. Graft survival defined as those participants who did not experience graft loss. Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

8. Secondary Outcome

Title	Change From Baseline in Diastolic Blood Pressure at Week 24
Description	Value at Week 24 minus value at baseline.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

9. Secondary Outcome

Title	Change From Baseline in Diastolic Blood Pressure at Week 52
Description	Value at Week 52 minus value at baseline.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

10. Secondary Outcome

Title	Change From Baseline in Diastolic Blood Pressure at Week 104
Description	Value at Week 104 minus value at baseline.
Time Frame	Baseline and Week 104

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

11. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure at Week 24
Description	Value at Week 24 minus value at baseline.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

12. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure at Week 52
Description	Value at Week 52 minus value at baseline.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

13. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure at Week 104
Description	Value at Week 104 minus value at baseline.
Time Frame	Baseline and Week 104

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

14. Secondary Outcome

Title	Change From Baseline in the Severity and Progression of Biopsy-Confirmed Chronic Allograft Nephropathy (CAN) at Week 104
Time Frame	Baseline and Week 104

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

15. Secondary Outcome

Title	Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 52
Time Frame	Weeks 52

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

16. Secondary Outcome

Title	Occurence of Acute Rejection or Premature Withdrawal From Study Medication for Any Reason by Week 104
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

17. Secondary Outcome

Title	Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 24
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

18. Secondary Outcome

Title	Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 52
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

19. Secondary Outcome

Title	Incidence and Severity of Biopsy-Confirmed Acute Rejection at Week 104
Time Frame	Week 104

Outcome Measure Data

Analysis Population Description

Insufficient or no data available for efficacy analyses because study was terminated early.

Arm/Group Title	Sirolimus (SRL)	Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.	Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Sirolimus (SRL)		Calcineurin Inhibitor (CI)
Arm/Group Description	SRL added to the immunosuppressive regimen at a daily maintenance dose of 2 mg, following a loading dose of 6 mg. The dose of SRL adjusted as necessary to maintain a whole blood trough concentration range of 10 to 15 ng/mL. CI dose was reduced by 50% and discontinued within 2 weeks if SRL at the target trough level. Once SRL trough level was at target range, MMF dose reduced to a maximum of 1500 mg/day or MPS dose reduced to a maximum of 1080 mg/day and AZA dose reduced to a maximum of 75 mg/day. Corticosteroids were administered according to local practice, within a daily maintenance dosage range (2.5 to 15 mg for prednisone or prednisolone; 2 to 12 mg/day for methylprednisolone) or the alternate day equivalent.		Patients will continue to receive a CI (tacrolimus or CsA). At the discretion of the investigator, patients will be permitted to: (a) change from MMF/MPS to AZA or vice versa, and from CsA to tacrolimus or vice versa; (b) continue MMF/MPS or AZA for the entire 104-week period of randomized therapy; or (c) discontinue MMF/MPS or AZA and subsequently restart either one after discontinuation. Whole blood CsA or tacrolimus trough concentrations will be monitored at designated intervals and the CI dose adjusted to maintain the following trough concentration ranges: CsA 50-250 ng/mL and Tacrolimus 4-10 ng/mL.
All Cause Mortality
	Sirolimus (SRL)		Calcineurin Inhibitor (CI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sirolimus (SRL)		Calcineurin Inhibitor (CI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/21 (28.6%)		2/10 (20%)
Eye disorders
Lens dislocation	0/21 (0%)		1/10 (10%)
Gastrointestinal disorders
Mechanical ileus	1/21 (4.8%)		0/10 (0%)
Appendicitis	0/21 (0%)		1/10 (10%)
General disorders
Pyrexia	1/21 (4.8%)		0/10 (0%)
Cellulitis	1/21 (4.8%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	1/21 (4.8%)		0/10 (0%)
Pneumonitis	2/21 (9.5%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Sirolimus (SRL)		Calcineurin Inhibitor (CI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/21 (371.4%)		18/10 (180%)
Blood and lymphatic system disorders
Leukopenia	2/21 (9.5%)		0/10 (0%)
Epistaxis	2/21 (9.5%)		0/10 (0%)
Eye disorders
Eyelid oedema	2/21 (9.5%)		0/10 (0%)
Gastrointestinal disorders
Diarrhoea	3/21 (14.3%)		2/10 (20%)
Haemorrhoids	2/21 (9.5%)		0/10 (0%)
Mouth ulceration	11/21 (52.4%)		2/10 (20%)
Tooth ache	2/21 (9.5%)		0/10 (0%)
General disorders
Herpes virus infection	2/21 (9.5%)		1/10 (10%)
Hepatobiliary disorders
Hepatic function abnormal	3/21 (14.3%)		0/10 (0%)
Investigations
Aspartate aminotransferase increased	2/21 (9.5%)		0/10 (0%)
Metabolism and nutrition disorders
Hyperlipidaemia	10/21 (47.6%)		3/10 (30%)
Hyperuricaemia	2/21 (9.5%)		3/10 (30%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/21 (19%)		0/10 (0%)
Nervous system disorders
Dizziness	2/21 (9.5%)		0/10 (0%)
Insomina	3/21 (14.3%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	11/21 (52.4%)		6/10 (60%)
Cough	7/21 (33.3%)		1/10 (10%)
Pharyngolaryngeal pain	2/21 (9.5%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Acne	8/21 (38.1%)		1/10 (10%)
Rash	3/21 (14.3%)		0/10 (0%)

Limitations/Caveats

Study terminated early due to difficulties in enrolling qualified patients. No patients completed 104 weeks (primary outcome); a few completed 60 weeks. Insufficient data were available for efficacy analyses.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.