Study to Assess the Effect of Sodium Zirconium Cyclosilicate on the Pharmacokinetics of Tacrolimus and Cyclosporin in Healthy Subjects

Hyperkalaemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04788641
• Other study ID #: D9480C00012
• Secondary ID: 2020-000515-68
• Status: Completed
• Phase: Phase 1
• Start date: March 30, 2021
• Est. completion date: September 16, 2021

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: September 16, 2021
• Est. primary completion date: September 16, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperkalaemia
• Hyperkalemia

Intervention

Drug:
• Tacrolimus
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.
• Cyclosporin
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.
• Sodium Zirconium Cyclosilicate
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.

Locations

Country	Name	City	State
Germany	Research Site	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Concentration (Cmax)	Effect of co-administered SZC on the Cmax of tacrolimus and cyclosporin in healthy participants was determined.	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
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.	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	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.	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	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.	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	Half-life Associated With Terminal Slope (?z) of a Semi-logarithmic Concentration-time Curve (t½?z)	Effect of co-administered SZC on the t½?z of tacrolimus and cyclosporin in healthy participants was determined.	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	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.	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]

External Links

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