Hyperkalaemia
Conditions
Keywords
Pharmacokinetics, Sodium Zirconium Cyclosilicate, Tacrolimus, Cyclosporin, Drug-drug interaction study
Brief summary
This study will be an open-label, randomised sequence, 2-period, 2-cohort, 2-treatment in each cohort, cross-over study in healthy subjects (males and females of non-childbearing potential), performed at a single study centre.
Detailed description
The study will comprise: * A screening period of maximum 28 days; * Two treatment periods: * Treatment Period 1 starts with admission to the Clinical Unit on Day -1, followed by dosing on Day 1 with the assigned treatment (A, B, C, or D) as per assigned cohort and treatment sequence, followed by a washout period of at least 14 days. * Treatment Period 2 starts with admission to Clinical Unit on Day -1, followed by dosing on Day 1 with cross-over treatment as per assigned cohort, followed by a follow-up period of 7 to 10 days. * A follow-up visit/early termination visit at 7 to 10 days after the last investigation medicinal product (IMP) administration. Subjects will be assigned to either Cohort 1 (tacrolimus) or to Cohort 2 (cyclosporin). Each cohort will have 2 treatment periods. Subjects in each cohort will be randomly assigned to one of 2 treatment sequences (AB\|BA or CD\|DC) where, * Treatment A: Tacrolimus * Treatment B: Tacrolimus + SZC * Treatment C: Cyclosporin * Treatment D: Cyclosporin + SZC
Interventions
DRUGTacrolimus
Each subject in this cohort will receive a single dose of oral capsules of tacrolimus on 2 occasions, once alone and once in combination with oral suspension of SZC. Drug administrations will occur after a 12 hour overnight fast.
DRUGCyclosporin
Each subject will receive a single dose of oral capsules of cyclosporin on 2 occasions, once alone and once in combination with oral suspension of SZC. Drug administrations will occur after a 12 hour overnight fast.
Each subject will receive single oral doses of SZC with tacrolimus (cohort 1) or cyclosporin (cohort 2) under fasted conditions. The doses will be administered after an overnight fast of at least 12 hours.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
• Healthy male and female subjects aged 18 to 50 years (both inclusive)
Exclusion criteria
* History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study. * History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. * Any clinically important abnormalities in rhythm, conduction or morphology of the 12-lead safety electrocardiogram (ECG), at screening visit and/or admission to the Clinical Unit. * Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. * History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to SZC, tacrolimus, or cyclosporin. * Subjects who have previously received SZC.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) | Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin | Effect of co-administered SZC on the Cmax of tacrolimus and cyclosporin in healthy participants was determined. |
| Area Under Concentration-time Curve From Time Zero to Infinity (AUCinf) | Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin | Effect of co-administered SZC on the AUCinf of tacrolimus and cyclosporin in healthy participants was determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin | Effect of co-administered SZC on the AUClast of tacrolimus and cyclosporin in healthy participants was determined. |
| Time to Reach Maximum Observed Concentration Following Drug Administration (Tmax) | Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin | Effect of co-administered SZC on the tmax of tacrolimus and cyclosporin in healthy participants was determined. |
| Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin | Effect of co-administered SZC on the t½λz of tacrolimus and cyclosporin in healthy participants was determined. |
| Number of Participants With Adverse Events (AEs) and Serious AEs | From the time of IMP administration (Day 1) to Follow-up/Early Termination Visit (7-10 days after last IMP administration) [up to 4 weeks] | Safety and tolerability of co-administration of SZC and tacrolimus/cyclosporin as compared to tacrolimus/cyclosporin alone was assessed. |
Countries
Germany
Participant flow
Recruitment details
The study was conducted at a single study centre (Berlin, Germany) between 30 March 2021 to 16 September 2021.
Pre-assignment details
Participants who met all the inclusion and none of the exclusion criteria were randomized at single center. The screening period was from Day -28 to Day -2. All participants signed and dated the Informed consent form before any study procedures were performed. All the study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Tacrolimus): Treatment A, Then Treatment B Participants received a single dose of oral capsules of Tacrolimus on 2 occasions once alone (Treatment A: Tacrolimus) in Treatment Period 1 on Day 1 and once in combination with oral suspension of SZC (Treatment B: Tacrolimus+ SZC) in Treatment Period 2 on Day 1 separated by at least 14 days. Participants had a follow-up period of 7 to 10 days. | 16 |
| Cohort 1 (Tacrolimus): Treatment B, Then Treatment A Participants received a single dose of oral capsules of Tacrolimus on 2 occasions once in combination with oral suspension of SZC (Treatment B: Tacrolimus + SZC) in Treatment Period 2 on Day 1 and once alone (Treatment A: Tacrolimus) in Treatment Period 1 on Day 1 and separated by at least 14 days. Participants had a follow-up period of 7 to 10 days. | 15 |
| Cohort 2 (Cyclosporin): Treatment C, Then Treatment D Participants received a single dose of oral capsules of Cyclosporin on 2 occasions once alone (Treatment C: Cyclosporin) in Treatment Period 1 on Day 1 and once in combination with oral suspension of SZC (Treatment D: Cyclosporin + SZC) in Treatment Period 2 on Day 1 separated by at least 14 days. Participants had a follow-up period of 7 to 10 days. | 16 |
| Cohort 2 (Cyclosporin): Treatment D, Then Treatment C Participants received a single dose of oral capsules of Cyclosporin on 2 occasions once in combination with oral suspension of SZC (Treatment D: Cyclosporin + SZC) in Treatment Period 2 on Day 1 and once alone (Treatment C: Cyclosporin) in Treatment Period 1 on Day 1 and separated by at least 14 days. Participants had a follow-up period of 7 to 10 days. | 15 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 2 (4 Days) | Adverse Event | 0 | 0 | 1 | 0 |
| Treatment Period 2 (4 Days) | Participant decided to discontinue further participation | 1 | 0 | 0 | 0 |
| Treatment Period 2 (4 Days) | Protocol Violation | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 (Tacrolimus): Treatment A, Then Treatment B | Cohort 1 (Tacrolimus): Treatment B, Then Treatment A | Total | Cohort 2 (Cyclosporin): Treatment C, Then Treatment D | Cohort 2 (Cyclosporin): Treatment D, Then Treatment C |
|---|---|---|---|---|---|
| Age, Continuous Cohort 1 (Tacrolimus) | 38.3 years STANDARD_DEVIATION 8.9 | 37.1 years STANDARD_DEVIATION 9.6 | 37.7 years STANDARD_DEVIATION 9.1 | — | — |
| Age, Continuous Cohort 2 (Cyclosporin) | — | — | 32.1 years STANDARD_DEVIATION 8.6 | 33.2 years STANDARD_DEVIATION 9 | 30.9 years STANDARD_DEVIATION 8.3 |
| Age, Customized 18 - 50 years | 16 Participants | 15 Participants | 62 Participants | 16 Participants | 15 Participants |
| Age, Customized 51 years and older | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 16 Participants | 15 Participants | 61 Participants | 15 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 15 Participants | 54 Participants | 12 Participants | 13 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 59 Participants | 16 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 | 0 / 31 | 0 / 29 |
| other Total, other adverse events | 7 / 31 | 13 / 30 | 8 / 31 | 7 / 29 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 | 0 / 31 | 0 / 29 |
Outcome results
Primary
Area Under Concentration-time Curve From Time Zero to Infinity (AUCinf)
Effect of co-administered SZC on the AUCinf of tacrolimus and cyclosporin in healthy participants was determined.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin
Population: The PK analysis set consisted of all participants in the safety analysis set and who had at least 1 quantifiable whole blood concentration post-dose for tacrolimus (Cohort 1) or for cyclosporin (Cohort 2) and who had no major protocol deviations thought to impact on the analysis of the PK data.~Here, overall number of participants analyzed are the participants with available data that were analyzed for the outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Tacrolimus (5 mg) | Area Under Concentration-time Curve From Time Zero to Infinity (AUCinf) | 267900 Picogram.hour/milliliter | Geometric Coefficient of Variation 50.2 |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Area Under Concentration-time Curve From Time Zero to Infinity (AUCinf) | 171700 Picogram.hour/milliliter | Geometric Coefficient of Variation 48.95 |
| Treatment C: Cyclosporin (100 mg) | Area Under Concentration-time Curve From Time Zero to Infinity (AUCinf) | 1884 Picogram.hour/milliliter | Geometric Coefficient of Variation 25.9 |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Area Under Concentration-time Curve From Time Zero to Infinity (AUCinf) | 1810 Picogram.hour/milliliter | Geometric Coefficient of Variation 23.91 |
Comparison: Tacrolimus90% CI: [55.64, 71.13]
Comparison: Cyclosporin90% CI: [92.93, 101.7]
Primary
Maximum Observed Concentration (Cmax)
Effect of co-administered SZC on the Cmax of tacrolimus and cyclosporin in healthy participants was determined.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin
Population: The PK analysis set consisted of all participants in the safety analysis set and who had at least 1 quantifiable whole blood concentration post-dose for tacrolimus (Cohort 1) or for cyclosporin (Cohort 2) and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Tacrolimus (5 mg) | Maximum Observed Concentration (Cmax) | 27140 Picogram/milliliter (pg/ml) | Geometric Coefficient of Variation 37.61 |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Maximum Observed Concentration (Cmax) | 19350 Picogram/milliliter (pg/ml) | Geometric Coefficient of Variation 35.88 |
| Treatment C: Cyclosporin (100 mg) | Maximum Observed Concentration (Cmax) | 593.6 Picogram/milliliter (pg/ml) | Geometric Coefficient of Variation 19.54 |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Maximum Observed Concentration (Cmax) | 608.1 Picogram/milliliter (pg/ml) | Geometric Coefficient of Variation 25.28 |
Comparison: Tacrolimus90% CI: [65.44, 77.24]
Comparison: Cyclosporin90% CI: [96.11, 110.1]
Secondary
Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
Effect of co-administered SZC on the AUClast of tacrolimus and cyclosporin in healthy participants was determined.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin
Population: The PK analysis set consisted of all participants in the safety analysis set and who had at least 1 quantifiable whole blood concentration post-dose for tacrolimus (Cohort 1) or for cyclosporin (Cohort 2) and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Tacrolimus (5 mg) | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 240800 Picogram.hour/milliliter | Geometric Coefficient of Variation 50.79 |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 159000 Picogram.hour/milliliter | Geometric Coefficient of Variation 51.13 |
| Treatment C: Cyclosporin (100 mg) | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 1792 Picogram.hour/milliliter | Geometric Coefficient of Variation 26.46 |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | 1718 Picogram.hour/milliliter | Geometric Coefficient of Variation 24.39 |
Comparison: Tacrolimus90% CI: [58.69, 73.24]
Comparison: Cyclosporin90% CI: [92.7, 101.6]
Secondary
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
Effect of co-administered SZC on the t½λz of tacrolimus and cyclosporin in healthy participants was determined.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin
Population: The PK analysis set consisted of all participants in the safety analysis set and who had at least 1 quantifiable whole blood concentration post-dose for tacrolimus (Cohort 1) or for cyclosporin (Cohort 2) and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Tacrolimus (5 mg) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 33.59 hour | Geometric Coefficient of Variation 18.72 |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 33.31 hour | Geometric Coefficient of Variation 22.27 |
| Treatment C: Cyclosporin (100 mg) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 9.223 hour | Geometric Coefficient of Variation 32.78 |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 8.647 hour | Geometric Coefficient of Variation 31.12 |
Comparison: Tacrolimus90% CI: [94.62, 102.4]
Comparison: Cyclosporin90% CI: [85.74, 103.3]
Secondary
Number of Participants With Adverse Events (AEs) and Serious AEs
Safety and tolerability of co-administration of SZC and tacrolimus/cyclosporin as compared to tacrolimus/cyclosporin alone was assessed.
Time frame: From the time of IMP administration (Day 1) to Follow-up/Early Termination Visit (7-10 days after last IMP administration) [up to 4 weeks]
Population: All participants who received at least 1 dose of IMP were included in the safety analysis for the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: Tacrolimus (5 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to discontinuation of IMP | 0 Participants |
| Treatment A: Tacrolimus (5 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE with outcome = death | 0 Participants |
| Treatment A: Tacrolimus (5 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to withdrawal from study | 0 Participants |
| Treatment A: Tacrolimus (5 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment A: Tacrolimus (5 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE | 7 Participants |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to discontinuation of IMP | 0 Participants |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to withdrawal from study | 0 Participants |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE with outcome = death | 0 Participants |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE | 13 Participants |
| Treatment C: Cyclosporin (100 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment C: Cyclosporin (100 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE | 8 Participants |
| Treatment C: Cyclosporin (100 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE with outcome = death | 0 Participants |
| Treatment C: Cyclosporin (100 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to discontinuation of IMP | 1 Participants |
| Treatment C: Cyclosporin (100 mg) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to withdrawal from study | 1 Participants |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to discontinuation of IMP | 0 Participants |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE with outcome = death | 0 Participants |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE | 7 Participants |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any SAE (including events with outcome = death) | 0 Participants |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Number of Participants With Adverse Events (AEs) and Serious AEs | Any AE leading to withdrawal from study | 0 Participants |
Secondary
Time to Reach Maximum Observed Concentration Following Drug Administration (Tmax)
Effect of co-administered SZC on the tmax of tacrolimus and cyclosporin in healthy participants was determined.
Time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours post-dose of tacrolimus or cyclosporin
Population: The PK analysis set consisted of all participants in the safety analysis set and who had at least 1 quantifiable whole blood concentration post-dose for tacrolimus (Cohort 1) or for cyclosporin (Cohort 2) and who had no major protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: Tacrolimus (5 mg) | Time to Reach Maximum Observed Concentration Following Drug Administration (Tmax) | 1.75 hour |
| Treatment B: Tacrolimus (5 mg) and SZC (15 g) | Time to Reach Maximum Observed Concentration Following Drug Administration (Tmax) | 1.50 hour |
| Treatment C: Cyclosporin (100 mg) | Time to Reach Maximum Observed Concentration Following Drug Administration (Tmax) | 1.50 hour |
| Treatment D: Cyclosporin (100 mg) and SZC (15 g) | Time to Reach Maximum Observed Concentration Following Drug Administration (Tmax) | 1.25 hour |
Comparison: Tacrolimus90% CI: [73.38, 95.84]
Comparison: Cyclosporin90% CI: [87.16, 109.2]