The purpose of the study is to assess the safety, tolerability and the pharmacokinetics (PK) of AZD4063 after single dose administration in participants with phospholamban (PLN) R14del dilated cardiomyopathy.
This is a Phase 1, first in human, unblinded, ascending dose study which will consist of a SAD (single ascending dose) part and an Optional part. The SAD part of the study will assess the single doses of AZD4063 across 4 cohorts. It will consist of: * A Screening period * A Treatment period: The participants will receive a single dose of AZD4063 by subcutaneous (SC) injection * A Follow-up period Optional cohorts may be added based on emerging safety, PK and PD data of the preceding cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
AZD4063 will be administered as solution for injection via subcutaneous route of administration.
Research Site
Amsterdam, Netherlands
RECRUITINGResearch Site
Groningen, Netherlands
RECRUITINGResearch Site
Rotterdam, Netherlands
RECRUITINGNumber of participants with adverse events (AEs)
The safety and tolerability of AZD4063 following the SC administration of single doses in participants with PLN R14del dilated cardiomyopathy will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Area under plasma concentration-time curve from 0 to infinity (AUCinf)
The AUCinf of single ascending doses of AZD4063 following SC administration will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast)
The AUClast of single doses of AZD4063 following SC administration will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Maximum plasma drug concentration (Cmax)
The Cmax of single doses of AZD4063 following SC administration will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 80; Cohorts 3 and 4: Day 1 to 210
Renal clearance (CLR)
The CLR of the single doses of AZD4063 following SC administration will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)
Cumulative amount of analyte excreted (Ae)
The Ae of single doses of AZD4063 following SC administration will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)
Fraction of dose excreted unchanged in urine (Fe)
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Research Site
Utrecht, Netherlands
RECRUITINGThe Fe of single doses of AZD4063 following SC administration will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)
Change in endomyocardial biopsy PLN messenger ribonucleic acid (mRNA levels) from baseline to estimated peak knockdown and estimated return-to-baseline
The effects of single ascending doses of AZD4063 on knockdown of PLN mRNA will be evaluated.
Time frame: Cohorts 1 and 2: Day 1 to 94; Cohorts 3 and 4: Day 1 to Follow up (Day 224)