Clinical trial NCT04788641: Study to Assess the Effect of Sodium Zirconium Cyclosilicate on the Pharmacokinetics of Tacrolimus and Cyclosporin in Healthy Subjects
Official title: A Two-Cohort, Randomised Sequence, Cross-over, Open-label Study to Assess the Effect of a Single Dose of Sodium Zirconium Cyclosilicate (SZC) on the Pharmacokinetics of Tacrolimus and Cyclosporin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperkalaemia
Keywords: Pharmacokinetics
Sodium Zirconium Cyclosilicate
Tacrolimus
Cyclosporin
Drug-drug interaction study
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2021-03-09
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Concentration (Cmax)
timeFrame: 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
measure: Area Under Concentration-time Curve From Time Zero to Infinity (AUCinf)
timeFrame: 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
Secondary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)
timeFrame: 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
measure: Time to Reach Maximum Observed Concentration Following Drug Administration (Tmax)
timeFrame: 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
measure: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
timeFrame: 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
measure: Number of Participants With Adverse Events (AEs) and Serious AEs
timeFrame: 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]
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Research Site
Study officials:
affiliation: Parexel Early Phase Clinical Unit Berlin
name: Thomas Koernicke, Dr
role: PRINCIPAL_INVESTIGATOR
References: