Trial Outcomes & Findings for A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Kidney Transplant Patients (NCT NCT00282568)

Last Updated: 2013-09-26

Results Overview

The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the trapezoidal rule.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

70 participants

Primary outcome timeframe

For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

Results posted on

2013-09-26

Participant Flow

Stable, adult kidney transplant recipients being treated with tacrolimus (Prograf)-based immunosuppressive regimen.

Pharmacokinetic (PK) treatment period was from Day 1 - 35. Participants who completed the PK period were eligible to continue receiving tacrolimus MR in the extended treatment period, from Day 36 up to 60 months.

Participant milestones

Participant milestones
Measure	Tacrolimus Modified Release Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Pharmacokinetic Treatment Period STARTED	70
Pharmacokinetic Treatment Period Received Tacrolimus	68
Pharmacokinetic Treatment Period Received Tacrolimus MR	67
Pharmacokinetic Treatment Period COMPLETED	67
Pharmacokinetic Treatment Period NOT COMPLETED	3
Extended Treatment Period STARTED	66
Extended Treatment Period COMPLETED	42
Extended Treatment Period NOT COMPLETED	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Tacrolimus Modified Release Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Pharmacokinetic Treatment Period Discontinued prior to Day 1	2
Pharmacokinetic Treatment Period Enrolled erroneously	1
Extended Treatment Period Adverse Event	17
Extended Treatment Period Non-compliance	4
Extended Treatment Period Physician Decision	1
Extended Treatment Period Lost to Follow-up	2

Baseline Characteristics

A Study to Assess the Pharmacokinetics of a Modified-release Tacrolimus Based Immunosuppression Regimen in Stable Kidney Transplant Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Age Continuous	46.9 years STANDARD_DEVIATION 12.37 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Race/Ethnicity, Customized White	53 participants n=5 Participants
Race/Ethnicity, Customized Black	12 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Reason for End Stage Renal Disease Glomerulonephritis	16 participants n=5 Participants
Reason for End Stage Renal Disease Polycystic Kidney Disease	8 participants n=5 Participants
Reason for End Stage Renal Disease Hypertensive Nephrosclerosis	6 participants n=5 Participants
Reason for End Stage Renal Disease Immunoglobulin A Nephropathy	6 participants n=5 Participants
Reason for End Stage Renal Disease Diabetes	6 participants n=5 Participants
Reason for End Stage Renal Disease Systemic Lupus Erythematosis	5 participants n=5 Participants
Reason for End Stage Renal Disease Focal Segmental Glomerulonephritis	5 participants n=5 Participants
Reason for End Stage Renal Disease Tubular and Interstitial Disease	3 participants n=5 Participants
Reason for End Stage Renal Disease Unknown	1 participants n=5 Participants
Reason for End Stage Renal Disease Other	10 participants n=5 Participants
Type of Current Transplant Cadaver	43 participants n=5 Participants
Type of Current Transplant Living Related Donor	18 participants n=5 Participants
Type of Current Transplant Living Nonrelated Donor	5 participants n=5 Participants
Re-transplant No	61 participants n=5 Participants
Re-transplant Yes	5 participants n=5 Participants
History of Pre-Study Dialysis No	12 participants n=5 Participants
History of Pre-Study Dialysis Yes	54 participants n=5 Participants

PRIMARY outcome

Timeframe: For tacrolimus, Days 1 and 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Days 14 and 21 pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.

Population: The number of participants analyzed represents the Pharmacokinetic evaluable set, defined as patients with all five complete pharmacokinetic profiles (two tacrolimus and three tacrolimus MR).

The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the trapezoidal rule.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus Day 1: Tacrolimus	215.1 ng*hr/mL Standard Deviation 59.4
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus Day 7: Tacrolimus	206.6 ng*hr/mL Standard Deviation 58.4
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus Day 14: Tacrolimus MR	200.7 ng*hr/mL Standard Deviation 57.5
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus Day 21: Tacrolimus MR	197.6 ng*hr/mL Standard Deviation 47.5

PRIMARY outcome

Population: The number of participants analyzed represents the Pharmacokinetic evaluable set.

The maximum concentration was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Maximum Observed Concentration (Cmax) of Tacrolimus Day 1: Tacrolimus	17.2 ng/mL Standard Deviation 7.2
Maximum Observed Concentration (Cmax) of Tacrolimus Day 7: Tacrolimus	16.0 ng/mL Standard Deviation 6.5
Maximum Observed Concentration (Cmax) of Tacrolimus Day 14: Tacrolimus MR	14.3 ng/mL Standard Deviation 4.7
Maximum Observed Concentration (Cmax) of Tacrolimus Day 21: Tacrolimus MR	14.2 ng/mL Standard Deviation 5.1

PRIMARY outcome

Timeframe: Days 1 and 7 (tacrolimus) and Days 14 and 21 (tacrolimus MR), 24 hours post-dose.

Population: The number of participants analyzed represents the trough evaluable set defined as all patients with replicate trough measurements for both tacrolimus and tacrolimus MR.

The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 24-hour time point post- dose, prior to receiving the next dose.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Minimum Concentration of Tacrolimus (Cmin) Day 1: Tacrolimus	6.96 ng/mL Standard Deviation 1.90
Minimum Concentration of Tacrolimus (Cmin) Day 7: Tacrolimus	6.73 ng/mL Standard Deviation 1.99
Minimum Concentration of Tacrolimus (Cmin) Day 14: Tacrolimus MR	6.08 ng/mL Standard Deviation 1.80
Minimum Concentration of Tacrolimus (Cmin) Day 21: Tacrolimus MR	5.83 ng/mL Standard Deviation 1.63

PRIMARY outcome

Population: The number of participants analyzed represents the trough evaluable set defined as all patients with replicate trough measurements for both tacrolimus and tacrolimus MR.

The time to reach the maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Time to Maximum Observed Concentration of Tacrolimus (Tmax) Day 1: Tacrolimus	1.9 hours Standard Deviation 1.8
Time to Maximum Observed Concentration of Tacrolimus (Tmax) Day 7: Tacrolimus	2.0 hours Standard Deviation 1.7
Time to Maximum Observed Concentration of Tacrolimus (Tmax) Day 14: Tacrolimus MR	3.1 hours Standard Deviation 2.3
Time to Maximum Observed Concentration of Tacrolimus (Tmax) Day 21: Tacrolimus MR	2.7 hours Standard Deviation 2.1

PRIMARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Modified full analysis set, defined as all patients who took at least one dose of tacrolimus MR during the extension portion of the study.

Patient Survival defined as any participant who did not die by the time of analysis.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Patient Survival	95.45 percentage of participants Interval 90.43 to 100.0

PRIMARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Modified full analysis set, defined as all patients who took at least one dose of tacrolimus MR during the extension portion of the study.

Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participants death.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Graft Survival	86.36 percentage of participants Interval 78.08 to 94.64

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Modified full analysis set

Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Percentage of Participants With Biopsy-confirmed Acute Rejection	10.61 percentage of participants Interval 3.18 to 18.03

SECONDARY outcome

Timeframe: Baseline (the last day of tacrolimus on Day 7), Day 35 (end of the pharmacokinetic phase) and end of treatment (EOT; the last observed value during treatment, maximum time on study was 60 months).

Population: Modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus and at least one dose of tacrolimus MR during the pharmacokinetic portion of the study. "N" indicates the number of participants with available data at each time point."

Renal function was assessed using serum creatinine levels over the course of the study.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=67 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Change From Baseline in Serum Creatinine Baseline [N= 67]	1.37 mg/dL Standard Deviation 0.501
Change From Baseline in Serum Creatinine Change from Baseline at Day 35 [N=66]	0.09 mg/dL Standard Deviation 0.350
Change From Baseline in Serum Creatinine Change from Baseline at EOT [N=67]	0.57 mg/dL Standard Deviation 2.322

SECONDARY outcome

Population: Modified safety analysis set

Renal function was assessed using creatinine clearance levels calculated using the Cockcroft-Gault formula, over the course of the study.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=67 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Change From Baseline in Creatinine Clearance Baseline [N= 67]	62.29 mL/minute Standard Deviation 17.531
Change From Baseline in Creatinine Clearance Change from Baseline at Day 35 [N=66]	-2.32 mL/minute Standard Deviation 5.500
Change From Baseline in Creatinine Clearance Change from Baseline at EOT [N=67]	-5.41 mL/minute Standard Deviation 13.335

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Participants in the modified full analysis set who died on study.

For participants who died on study, the median number of days from enrollment to death due to any cause.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=3 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Time to Event for Patient Non Survival	1754.00 days Interval 1063.0 to 1799.0

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Participants in the modified full analysis set with graft loss.

For participants with graft loss, the median number of days from enrollment to graft loss. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis (for more than 30 days)) or participant death.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=9 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Time to Event for Graft Non Survival	1526.00 days Interval 130.0 to 2113.0

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Participants in the modified full analysis set with a biopsy-confirmed acute rejection.

For participants with a biopsy-confirmed acute rejection, the median number of days from enrollment to the date of biopsy confirmation. Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute allograft rejection that was confirmed by biopsy results and was Banff grade ≥ IA. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=7 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Time to First Biopsy-confirmed Acute Rejection	727.00 days Interval 163.0 to 1762.0

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Participants in the modified full analysis set with a biopsy-confirmed acute rejection.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=7 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Grade of Biopsy-confirmed Acute Rejection Episodes Grade IA	3 participants
Grade of Biopsy-confirmed Acute Rejection Episodes Grade IB	1 participants
Grade of Biopsy-confirmed Acute Rejection Episodes Grade IIA	2 participants
Grade of Biopsy-confirmed Acute Rejection Episodes Grade IIB	1 participants
Grade of Biopsy-confirmed Acute Rejection Episodes Grade III	0 participants

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Modified full analysis set

Steroid-resistant rejection episodes were treated with anti-lymphocyte antibodies. If a participant had a histologically proven Banff Grade II or III rejection, they could be initiated on anti-lymphocyte antibody treatment per institutional practice. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection	4 participants

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Modified full analysis set

This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Number of Participants With Multiple Rejection Episodes	2 participants

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Modified full analysis set

A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Number of Participants With Clinically Treated Acute Rejection Episodes	7 participants

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Due to the low number of participants with biopsy-confirmed acute rejection episodes, chronic rejection was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Treatment failure was defined as discontinuation of study drug for any reason. Due to discontinuation of the study by the sponsor, treatment failure was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Participants in the modified full analysis set with graft loss.

The primary reason for graft loss was recorded by the Investigator. Graft loss was defined as graft failure (re-transplant or permanent return to dialysis) or death. GBM = glomerular basement membrane.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=9 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Primary Reason for Graft Loss Donor GBM disease	1 participants
Primary Reason for Graft Loss Drug induced nephropathy	1 participants
Primary Reason for Graft Loss Polyoma virus	1 participants
Primary Reason for Graft Loss Renal insufficiency	1 participants
Primary Reason for Graft Loss Non-compliance with study medication	1 participants
Primary Reason for Graft Loss Recurrent disease	1 participants
Primary Reason for Graft Loss Death	3 participants

SECONDARY outcome

Timeframe: From enrollment until the end of study (up to 60 months).

Population: Modified full analysis set

Permanent dialysis defined as dialysis for longer than 30 days.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=66 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Number of Participants Returning to Permanent Dialysis	3 participants

SECONDARY outcome

Timeframe: From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months).

Population: Modified safety analysis set

An adverse event was defined as any reaction, side effect or other untoward medical occurrence, regardless of the relationship to study drug which occurred during the conduct of a clinical study. Clinically significant adverse changes in clinical status, routine laboratory studies or physical examinations were considered adverse events. A serious adverse event was any adverse event occurring at any dose that resulted in any of the following outcomes: * Death * Life-threatening adverse event * Inpatient hospitalization or prolongation of existing hospitalization * Persistent or significant disability or incapacity * Congenital abnormality or birth defect * Important medical event.

Outcome measures

Outcome measures
Measure	Tacrolimus Modified Release n=67 Participants Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs Any adverse event	66 participants
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs Any serious adverse event	39 participants
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs Adverse event leading to discontinuation	16 participants
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs Adverse Event leading to dose changes	29 participants
Safety as Assessed by Adverse Events, Laboratory Parameters and Vital Signs Death	3 participants

Adverse Events

Tacrolimus Modified Release

Serious events: 39 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tacrolimus Modified Release n=67 participants at risk Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Infections and infestations Cellulitis	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Escherichia urinary tract infection	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Pyelonephritis	4.5% 3/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Abscess limb	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Bronchitis	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Urosepsis	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Viral infection	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Cellulitis staphylococcal	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Clostridium colitis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Gastroenteritis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Gastroenteritis viral	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Hepatitis c	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Herpes zoster	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Human polyomavirus infection	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Influenza	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Orchitis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Pneumonia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Pneumonitis cryptococcal	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Pyelonephritis acute	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Sepsis syndrome	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Tracheobronchitis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Urinary tract infection	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Urinary tract infection bacterial	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Abdominal pain	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Nausea	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Vomiting	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Abdominal pain lower	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Abdominal strangulated hernia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Anal ulcer	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Coeliac disease	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Diarrhoea haemorrhagic	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Dysphagia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Gastritis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Intestinal perforation	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Palatal dysplasia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Small intestinal obstruction	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Nodule	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative disorder	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papilloma	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma stage unspecified	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsil cancer	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour lysis syndrome	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Renal and urinary disorders Renal failure acute	10.4% 7/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Renal and urinary disorders Haematuria	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Renal and urinary disorders Renal insufficiency	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Renal and urinary disorders Glomerulonephritis focal	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Renal and urinary disorders Renal failure chronic	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Renal and urinary disorders Tubulointestitial nephritis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Metabolism and nutrition disorders Dehydration	7.5% 5/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Metabolism and nutrition disorders Diabetic ketoacidosis	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Metabolism and nutrition disorders Fluid overload	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Metabolism and nutrition disorders Gout	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Metabolism and nutrition disorders Hyperkalaemia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Metabolism and nutrition disorders Hypervolaemia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Metabolism and nutrition disorders Hypovolaemia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Arteriovenous graft site complications	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Complications of transplant surgery	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Drug toxicity	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Incisional hernia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Injury	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Intentional misuse	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Medication error	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Post procedural diarrhoea	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Renal injury	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Tibia fracture	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Injury, poisoning and procedural complications Upper limb fracture	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Musculoskeletal and connective tissue disorders Localised osteoarthritis	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Musculoskeletal and connective tissue disorders Aseptic necrosis bone	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Musculoskeletal and connective tissue disorders Flank pain	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Musculoskeletal and connective tissue disorders Myopathy	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
General disorders Chest pain	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
General disorders Pyrexia	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
General disorders Asthenia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
General disorders Fatigue	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
General disorders Malaise	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
General disorders Pelvic mass	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Respiratory, thoracic and mediastinal disorders Bronchospasm	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Respiratory, thoracic and mediastinal disorders Dysphonia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Vascular disorders Malignant hypertension	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Vascular disorders Gangrene	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Vascular disorders Hypertension	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Vascular disorders Hypotension	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Vascular disorders Peripheral ischaemia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Cardiac disorders Angina pectoris	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Cardiac disorders Angina unstable	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Cardiac disorders Atrial Fibrillation	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Cardiac disorders Cardiac arrest	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Cardiac disorders Cardiac failure	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Cardiac disorders Cardiac failure congestive	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Cardiac disorders Myocardial infarction	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Investigations Blood creatinine increased	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Investigations Weight decreased	3.0% 2/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Blood and lymphatic system disorders Anaemia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Blood and lymphatic system disorders Leukopenia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Immune system disorders Amyloidosis	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Immune system disorders Kidney transplant rejection	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Reproductive system and breast disorders Vulvar Dysplasia	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Social circumstances Pregnancy of partner	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Surgical and medical procedures Renal transplant	1.5% 1/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.

Other adverse events

Other adverse events
Measure	Tacrolimus Modified Release n=67 participants at risk Participants were enrolled into the study on their stable twice-daily (bid) dose of tacrolimus on Day 1 and continued to receive a stable bid dose of tacrolimus through Day 7. Participants then converted to Tacrolimus Modified Release (MR), administered once daily at an equivalent dose to the patient's previous stable total daily dose of tacrolimus. Participants who completed the 4-week pharmacokinetic treatment period with tacrolimus MR could continue receiving tacrolimus MR as part of the extended treatment period of the study. Dose adjustments were allowed in order to maintain tacrolimus trough concentrations within the target range of 5 to 15 ng/mL and for clinical reasons.
Infections and infestations Upper respiratory tract infection	26.9% 18/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Sinusitis	13.4% 9/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Escherichia urinary tract infection	11.9% 8/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Nasopharyngitis	11.9% 8/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Influenza	10.4% 7/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Urinary tract infection bacterial	9.0% 6/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Urinary tract infection	7.5% 5/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Herpes zoster	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Pneumonia	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Infections and infestations Urinary tract infection enterococcal	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Diarrhoea	17.9% 12/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Nausea	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Gastrointestinal disorders Vomiting	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	7.5% 5/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Respiratory, thoracic and mediastinal disorders Cough	6.0% 4/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Vascular disorders Hypertension	10.4% 7/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
General disorders Oedema Peripheral	9.0% 6/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Investigations Blood creatinine increased	9.0% 6/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.
Nervous system disorders Headache	7.5% 5/67 • From the first dose of tacrolimus MR formulation through the day of last dose plus 10 days (approximately 60 months). Adverse events are reported for the modified safety analysis set defined as all patients who took at least 1 dose of tacrolimus MR during the pharmacokinetic period of the study.

Additional Information

Vice President, Therapeutic Area Head, Transplantation

Astellas Pharma Global Development, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or until 18 months have elapsed following study completion. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document.
Publication restrictions are in place

Restriction type: OTHER