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

Primary Purpose

Hyperkalaemia

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

Tacrolimus

Cyclosporin

Sodium Zirconium Cyclosilicate

About this trial

This is an interventional treatment trial for Hyperkalaemia focused on measuring Pharmacokinetics, Sodium Zirconium Cyclosilicate, Tacrolimus, Cyclosporin, Drug-drug interaction study

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Arm Description

Subjects in Cohort 1 will be randomised in a 1:1 ratio to receive one of the 2 treatment sequences and then cross-over to the other: tacrolimus alone (treatment A) followed by the combination treatment of tacrolimus and SZC (treatment B) or vice versa.

Subjects in Cohort 2 will be randomised in a 1:1 ratio to receive one of the 2 treatment sequences and then cross-over to the other: cyclosporin alone (treatment C) followed by the combination treatment of cyclosporin and SZC (treatment D) or vice versa.

Outcomes

Primary Outcome Measures

Maximum observed concentration (Cmax)

Effect of co-administered SZC on the Cmax of tacrolimus and cyclosporin in healthy subjects will be determined.

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 subjects will be determined.

Secondary Outcome Measures

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 subjects will be determined.

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 subjects will be determined.

Time to reach maximum observed concentration following drug administration (tmax)

Effect of co-administered SZC on the tmax of tacrolimus and cyclosporin in healthy subjects will be determined.

Number of subjects with adverse events (AEs) and serious AEs

Safety and tolerability of co-administration of SZC and tacrolimus/cyclosporin as compared to tacrolimus/cyclosporin alone will be assessed.

Full Information

NCT ID

NCT04788641

First Posted

March 5, 2021

Last Updated

May 9, 2022

Sponsor

AstraZeneca

Collaborators

Parexel

1. Study Identification

Unique Protocol Identification Number

NCT04788641

Brief Title

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

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

March 30, 2021 (Actual)

Primary Completion Date

September 16, 2021 (Actual)

Study Completion Date

September 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

Parexel

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperkalaemia

Keywords

Pharmacokinetics, Sodium Zirconium Cyclosilicate, Tacrolimus, Cyclosporin, Drug-drug interaction study

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

62 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Cyclosporin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Sodium Zirconium Cyclosilicate

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum observed concentration (Cmax)

Description

Effect of co-administered SZC on the Cmax of tacrolimus and cyclosporin in healthy subjects will be determined.

Time Frame

Treatment Periods 1 and 2: 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

Title

Area under concentration-time curve from time zero to infinity (AUCinf)

Description

Effect of co-administered SZC on the AUCinf of tacrolimus and cyclosporin in healthy subjects will be determined.

Time Frame

Treatment Periods 1 and 2: 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

Secondary Outcome Measure Information:

Title

Area under the concentration-time curve from time zero to time of last quantifiable concentration (AUClast)

Description

Effect of co-administered SZC on the AUClast of tacrolimus and cyclosporin in healthy subjects will be determined.

Time Frame

Treatment Periods 1 and 2: 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

Title

Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)

Description

Effect of co-administered SZC on the t½λz of tacrolimus and cyclosporin in healthy subjects will be determined.

Time Frame

Treatment Periods 1 and 2: 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

Title

Time to reach maximum observed concentration following drug administration (tmax)

Description

Effect of co-administered SZC on the tmax of tacrolimus and cyclosporin in healthy subjects will be determined.

Time Frame

Treatment Periods 1 and 2: 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

Title

Number of subjects with adverse events (AEs) and serious AEs

Description

Safety and tolerability of co-administration of SZC and tacrolimus/cyclosporin as compared to tacrolimus/cyclosporin alone will be assessed.

Time Frame

From screening (Days -28 to -2) to Follow-up/Early Termination Visit (7-10 days after last IMP administration)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Koernicke, Dr

Organizational Affiliation

Parexel Early Phase Clinical Unit Berlin

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Site

City

Berlin

ZIP/Postal Code

14050

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

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

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