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

NCT04788641 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: D9480C000122020-000515-68
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperkalaemia

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• 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

• 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

• 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

• 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]

Study Arms (2)

Cohort 1

EXPERIMENTAL

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.

Drug: Tacrolimus; Drug: Sodium Zirconium Cyclosilicate

Cohort 2

EXPERIMENTAL

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.

Drug: Cyclosporin; Drug: Sodium Zirconium Cyclosilicate

Interventions

Tacrolimus DRUG

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.

Cohort 1

Cyclosporin DRUG

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.

Cohort 2

Sodium Zirconium Cyclosilicate DRUG

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.

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects aged 18 to 50 years (both inclusive)

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

Related Links

• Protocol
• CSR Synopsis

MeSH Terms

Conditions

Hyperkalemia

Interventions

Tacrolimus; Cyclosporine; sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Thomas Koernicke, Dr

  Parexel Early Phase Clinical Unit Berlin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 9, 2021
• Study Start: March 30, 2021
• Primary Completion: September 16, 2021
• Study Completion: September 16, 2021
• Last Updated: April 5, 2024
• Results First Posted: April 5, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

DE (1)