Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours (AUC0-24h) for Tacrolimus (Part A) |
|
Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose |
|
Primary |
Number of Participants with Adverse Events (Part A + B) |
Safety is assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A serious AE (SAE) is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important. |
From first dose of study drug up to 7 days after last dose of study drug in Part B (up to 53 weeks) |
|
Primary |
Number of Participants with Adverse Events (Part C) |
Safety is assessed by adverse events (AEs), which includes abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induces clinical signs or symptoms, needs active intervention, interruption or discontinuation of study medication or is clinically significant. A serious AE (SAE) is an event resulting in death, persistent or significant disability/incapacity or congenital anomaly or birth defect, is life-threatening, requires or prolongs hospitalization or is considered medically important. |
Up to 9 years |
|
Secondary |
Maximum Concentration (Cmax) of Tacrolimus (Part A) |
|
Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose |
|
Secondary |
Time to Attain Maximum Concentration (tmax) of Tacrolimus (Part A) |
|
Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose |
|
Secondary |
Trough Concentration (C12) for Tacrolimus (Part A) |
|
Days 1, 7 and 28, 12 hours after dosing |
|
Secondary |
Trough Concentration (C24) for Tacrolimus (Part A) |
|
Days 1, 7 and 28, 24 hours after dosing |
|
Secondary |
Correlation between AUC24 & C24 (Part A) |
|
Days 1, 7 and 28 at predose, 1, 2, 4, 6, 12, 13, 14, 16, 18 and 24 hours postdose |
|
Secondary |
Number of Participants with Acute Rejections (Part A + B) |
Rejection episodes/acute rejections are indicated by clinical and/or laboratory signs, and are classified according to their rejection specific treatment: •Spontaneously Resolving Acute Rejection: not treated with new or increased corticosteroid medication, antibodies or any other medication and resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Sensitive Acute Rejection: treated with new or increased corticosteroid medication only and which has resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Resistant Acute Rejection: did not resolve following treatment with corticosteroids; - Resolved with further treatment: any acute rejection with an end date AND a treatment other than corticosteroid used; - Unresolved with further treatment: any acute rejection with no end date AND a treatment other than corticosteroid used; - Unresolved with no further treatment: any acute rejection with no end date AND ONLY corticosteroid treatment was used. |
Up to Week 52 |
|
Secondary |
Number of Participants with Biopsy-proven Acute Rejection Episodes (BPARs) (Part A + B) |
BPAR episodes are defined as acute rejection episodes confirmed by biopsy, and are classified according to their rejection specific treatment: •Spontaneously Resolving Acute Rejection: not treated with new or increased corticosteroid medication, antibodies or any other medication and resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Sensitive Acute Rejection: treated with new or increased corticosteroid medication only and which has resolved, irrespective of any tacrolimus dose changes; •Corticosteroid Resistant Acute Rejection: did not resolve following treatment with corticosteroids; - Resolved with further treatment: any acute rejection with an end date AND a treatment other than corticosteroid used; - Unresolved with further treatment: any acute rejection with no end date AND a treatment other than corticosteroid used; - Unresolved with no further treatment: any acute rejection with no end date AND ONLY corticosteroid treatment used. |
Up to Week 52 |
|
Secondary |
Severity of Biopsy Proven Acute Rejection Episodes (Part A + B) |
The severity of BPARs is categorized with specific criteria by organ: For kidney transplant participants, according to Banff '97 Diagnostic categories for renal allograft biopsies - Banff '07 update (C4d deposition, Acute antibody-mediated rejection I, II, and III, Acute T cell mediated rejection IA, IB, IIA, IIB and III); for liver transplant participants, according to 1997 Banff Schema for Grading of Liver Allograft Rejection - Rejection Activity Index (mild, moderate, severe or indeterminate/borderline); for heart, according to Standardized Nomenclature of the International Society of Heart and Lung Transplantation - Standardised Cardiac Biopsy Grading: Acute Cellular Rejection 2004 (mild, moderate, severe). |
Up to Week 52 |
|
Secondary |
Patient Survival (Part A + B) |
Patient survival is defined as the time from first dose of study drug to the date of death from any cause. |
Up to Week 52 |
|
Secondary |
Graft Survival (Part A + B) |
Graft survival is defined as the time from the first dose of study drug to graft loss. Graft loss is defined as retransplantation, nephrectomy (in case of kidney transplantation), death or dialysis (in case of kidney transplantation) ongoing at end of study or at discontinuation, unless superseded by follow-up information. |
Up to Week 52 |
|
Secondary |
Efficacy Failure (Part A + B) |
Efficacy failure is defined as the composite of the following: death, graft loss, BPAR and unknown outcome. A participant is considered to have an unknown outcome if he/she does not have the event of interest (death, graft loss, BPAR) or does not have a study assessment prior to day 335. |
Up to Week 52 |
|