| Primary | Percentage of Participants With Improvement of Greater Than or Equal to [≥]5 Milliliters Per Minute Per 1.73 Square Meters (mL/Min/m^2) in Calculated Glomerular Filtration Rate (GFR) at 24 Months Post-Transplantation (On-Therapy Analysis) | GFR was calculated using the Modified Diet in Renal Disease (MDRD) equation using either serum creatinine traceable to isotope dilution mass spectrometry (IDMS) or serum creatinine not traceable to IDMS. | On-Therapy Population (24 Months): all randomized participants who remained on assigned study therapy through 24 months post-transplantation. | Posted | | Number | | percentage of participants | | Baseline, Month 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
| | | Title | Denominators | Categories |
|---|
| | |
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | Fisher Exact | | 0.239 | Two-sided alpha equals (=) 0.05. | Odds Ratio (OR) | 0.7 | | | 2-Sided | 95 | 0.4 | 1.3 | | | | No | Superiority or Other | | |
|
| Secondary | Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 Months Post-Transplantation (On-Therapy Analysis) | GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. | On-Therapy Population (12 Months): all randomized participants who remained on assigned study therapy through 12 months post-transplantation. | Posted | | Number | | percentage of participants | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation (Intent-to-Treat [ITT] Analysis) | GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. | ITT Population: all randomized participants who received at least 1 dose of the assigned therapy after randomization. Missing GFR was imputed as follows: 1) GFR equals (=)0 after graft loss and 2) last observed value prior to missing was carried forward for death (with functioning graft), early termination or skipped assessment. | Posted | | Number | | percentage of participants | | Baseline, Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With Improvement of ≥7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation | GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. | ITT Population. Missing GFR was imputed as follows: 1) GFR=0 after graft loss and 2) last observed value prior to missing was carried forward for death (with functioning graft), early termination or skipped assessment. | Posted | | Number | | percentage of participants | | Baseline, Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 |
|
| Secondary | Percentage of Participants With Improvement of ≥10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation | GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. | ITT Population. Missing GFR was imputed as follows: 1) GFR=0 after graft loss and 2) last observed value prior to missing was carried forward for death (with functioning graft), early termination or skipped assessment. | Posted | | Number | | percentage of participants | | Baseline, Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 |
|
| Secondary | Calculated GFR Using MDRD (On-Therapy Analysis) | GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article. | On-Therapy Population: all participants who remained on assigned study therapy up to the point of discontinuation. number (n)=number of participants assessed for the specified parameter at a given visit. | Posted | | Mean | Standard Deviation | mL/min/1.73 m^2 | | Baseline, Months 6, 12, 18, and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 |
|
| Secondary | Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis) | GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article. | On-Therapy Population; n=number of participants assessed for the specified parameter at a given visit. | Posted | | Mean | Standard Error | mL/min/1.73 m^2 | | Baseline, Months 6, 12, 18, and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis) | GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Timepoints were calculated as study days, relative to the time of randomization of study medication. All available on-therapy values were included. Observed data were multiplied by a scale factor of 365, expressing the slope as an annual change. | On-Therapy analysis of the slope comprised the data collected from the on-therapy evaluations for all the participants in the ITT population; data collected from participants receiving sirolimus during the first 3 weeks post-randomization for safety monitoring were excluded from the analysis. | Posted | | Mean | 95% Confidence Interval | mL/min/1.73 m^2 per year | | Baseline, Month 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Serum Creatinine (On-Therapy Analysis) | Serum creatinine was measured in micromillimoles per liter (mcmol/L). Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article. | On-Therapy Population: all participants who remained on assigned study therapy up to the point of discontinuation. n=number of participants assessed for the specified parameter at a given visit. | Posted | | Mean | Standard Deviation | mcmol/L | | Baseline, Months 6, 12, 18, and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Change From Randomization in Serum Creatinine (On-Therapy Analysis) | Serum creatinine was measured in mcmol/L. Baseline was defined as the last assessment prior to first administration of study drug. | On-Therapy Population: all participants who remained on assigned study therapy up to the point of discontinuation. n=number of participants assessed for the specified parameter at a given visit. | Posted | | Mean | Standard Error | mcmol/L | | Baseline, Months 6, 12, 18, and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation | Biopsy-confirmed acute rejection was defined according to updated Banff criteria (2007) for renal allograft rejection. Graft loss was defined as physical loss (nephrectomy or retransplantation), functional loss (requiring dialysis for greater than or equal to [≥]56 days with no return of graft function), or death. | | Posted | | Number | | percentage of participants | | Post-randomization to Month 24 post-transplantation | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 |
|
| Secondary | Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization | Graft loss was defined as physical loss (nephrectomy or retransplantation), functional loss (requiring dialysis for ≥56 days with no return of graft function), or death. | | Posted | | Number | | percentage of participants | | Post-randomization to Months 12 and 24 Post-Transplantation | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation | BCAR was defined according to updated Banff criteria (2007) for renal allograft rejection. | | Posted | | Number | | percentage of participants | | Post-Randomization to 6, 12, 18, and 24 months Post-Transplantation | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months | Defined as the first BCAR occurring during the On-Therapy period based on the ITT population. Time to first BCAR was the days from transplantation to the date of BCAR. | | Posted | | Number | | percentage of participants | | Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant | BCAR was categorized as antibody-mediated (AM) or T-cell. AM BCAR severity was graded as Grade I (mild), Grade II (moderate), and Grade III (severe). T-cell BCAR severity was graded as 'Grade Ia, Ib (mild), Grade IIa, IIb (moderate), and Grade III (severe). If a participant had both T-cell BCAR and antibody-mediated BCAR on the first rejection, the participant was counted in each category. | | Posted | | Number | | participants | | Months 6, 12, 18, and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | |
|
| Secondary | Percentage of Participants With Antibody Use in Treatment of Acute Rejection | Number of participants who experienced an adverse event (AE) of rejection was used as the denominator in the determination of percentage of participants with antibody use in treatment of acute rejection. | Safety Population; only participants with an AE of rejection were included in the analysis. | Posted | | Number | | percentage of participants | | On Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 |
|
| Secondary | Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia | Anemia was defined as hemoglobin less than or equal to (≤)10 grams per deciliter (g/dL); leukopenia was defined as white blood cell (WBC) count ≤2000 per cubic millimeters (/mm^3); and thrombocytopenia was defined as platelets ≤100,000/mm^3. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article. | Safety Population; n=number of participants assessed for the specified parameter at a given visit. | Posted | | Number | | percentage of participants | | Baseline, Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | |
|
| Secondary | Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) | Parameters assessed included total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C); collected when participant was in a fasting state. | Safety Population; n=number of participants assessed for the specified parameter at a given visit. | Posted | | Mean | Standard Error | mmol/L | | Baseline, Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) | | | Posted | | Number | | percentage of participants | | Baseline, Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr) | Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article. | Safety Population; n=number of participants assessed for the specified parameter at a given visit. | Posted | | Mean | Standard Deviation | UPr/Cr | | Baseline and Months 12 and 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use | Included ACEI or ARB use prior to randomization, during the on-therapy period (up to 19 to 21 months post randomization) and the off-therapy period (up to 24 months post-transplantation). | | Posted | | Number | | percentage of participants | | Pre-randomization, On-Therapy Period (up to 21 months post-randomization), and Off-Therapy Period (up to 24 months post-transplantation) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Percentage of Participants With Stomatitis | Includes adverse events based on categorization by the investigator as stomatitis, regardless of the event preferred term in Medical Dictionary for Regulatory Activities (MedDRA) | | Posted | | Number | | percentage of participants | | From randomization up to 24 months after transplantation (On-Therapy) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type | Included treatments (analgesics, dental paste, topical antifungal, topical steroids, or other) prior to randomization, during the on-therapy period (up to 19 to 21 months post-randomization) and the off-therapy period (up to 24 months post-transplantation). | | Posted | | Number | | percentage of participants | | On-Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L]) | Ratio of hemoglobin A1c to normal hemoglobin. | | Posted | | Mean | Standard Error | L/L | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L) | | | Posted | | Mean | Standard Error | mmol | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L]) | | | Posted | | Mean | Standard Error | pmol/L | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg]) | | | Posted | | Mean | Standard Error | kg | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm]) | | | Posted | | Mean | Standard Error | cm | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting) | The HOMA-IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA-IR = fasting plasma glucose (mmol/L) multiplied by (*) fasting plasma insulin in microunits per liter (µU/L) divided by (/) 22.5. Participants taking insulin within 12 hours were excluded from the analysis. | | Posted | | Mean | Standard Error | insulin resistance score | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting) | The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population. HOMA-B = 20 * insulin (µU/L) / fasting plasma glucose (mmol/L) minus (-) 3.5 Participants taking insulin within 12 hours were excluded from the analysis. | | Posted | | Mean | Standard Error | percentage beta cell function | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus |
|
| Secondary | Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2]) | BMI = Weight (kg)/(Height*Height) (square meters [m^2]). | | Posted | | Mean | Standard Error | kg/m^2 | | Baseline, Month 12 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With New-Onset Diabetes | Participants were considered as having new onset diabetes during the On-therapy period if any of the below events emerged from baseline to Month 24: 1) at least 30 days continuous, or at least 25 days non-stop (without gap) use of any diabetic treatment after randomization; 2) a fasting glucose greater than or equal to (≥)126 milligrams per deciliter (mg/dL) after randomization; or 3) a non-fasting glucose ≥200 mg/dL after randomization, were included in the new-onset diabetes population. Events at Months 12 or 24 occurred from baseline to On-therapy Month 12 and from On-therapy Months 12 to 24, respectively. | Safety Population; participants at risk of new-onset diabetes mellitus at the beginning of the analysis interval were included and those with pre-existing diabetes were excluded from the analysis. n=number of participants assessed for the specified parameter at a given visit. | Posted | | Number | | percentage of participants | | From Baseline to On-Therapy Month 12, from Baseline to On-Therapy Month 24, and from On-Therapy Month 12 up to On-Therapy Month 24 | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin) | Participants were considered as having new onset diabetes during the On-therapy period if any of the below events emerged between baseline and Month 12 or Month 24: 1) at least 30 days continuous, or at least 25 days non-stop (without gap) use of any diabetic treatment after randomization; 2) a fasting glucose ≥126 mg/dL after randomization; or 3) a non-fasting glucose ≥200 mg/dL after randomization. | Safety Population. Only participants with new-onset diabetes mellitus at the beginning of the analysis interval were included; those with pre-existing diabetes were excluded from the analysis. | Posted | | Number | | percentage of participants | | 12 Months and 24 Months | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With Infection | Includes adverse events based on categorization by the investigator as 'infection', regardless of the event preferred term in MedDRA. | | Posted | | Number | | percentage of participants | | From randomization up to 24 months after transplantation (On-Therapy) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With Cytomegalovirus (CMV) Infection | Includes adverse event terms reported by the investigator to be attributed to the organism 'cytomegalovirus', regardless of the preferred term in MedDRA. | | Posted | | Number | | percentage of participants | | From randomization up to 24 months after transplantation (On-Therapy) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With Polyomavirus Infection | Includes adverse event terms reported by the investigator to be attributed to the organism 'polyomavirus', regardless of the preferred term in MedDRA. | | Posted | | Number | | percentage of participants | | From randomization up to 24 months after transplantation (On-Therapy) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
|
| Secondary | Percentage of Participants With Malignancy | Includes any adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferred term in MedDRA. | | Posted | | Number | | percentage of participants | | From randomization up to 24 months after transplantation (On-Therapy) | | | | ID | Title | Description |
|---|
| OG000 | Sirolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. | | OG001 | Tacrolimus | Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center's standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant. |
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