Pharmacokinetics and Pharmacodynamics of Two Prolonged-release Formulations of Vamifeport in Healthy Adults

CSL Behring22 enrolled

Overview

This is a phase 1, single-center, randomized, open-label study to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and safety of vamifeport after multiple oral administrations of one immediate-release (IR) formulation and after single and multiple oral administrations of two prolonged-release (PR) formulation in healthy adult participants.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy Volunteers

Interventions

Vamifeport IRFDRUG

Vamifeport IRF will be administered orally as per the dosing levels and formulations for respective treatment periods.

Vamifeport PR1DRUG

Vamifeport PR1 will be administered orally as per the dosing levels and formulations for respective treatment periods.

Vamifeport PR2DRUG

Vamifeport PR2 will be administered orally as per the dosing levels and formulations for respective treatment periods.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Aged greater than or equal to (\>=) 18 to less than or equal to (\<=) 60 years when providing written informed consent. * Healthy, as determined by the investigator based on review of defined assessments during Screening. * Body weight between 50 and 100 kilograms (kg) (inclusive) and body mass index within the range 18.0 to 32.0 kg per meter squared (kg/m2) (inclusive) at Screening and Day -1. Exclusion Criteria: * Any clinically relevant abnormal 12-lead ECG finding at Screening or Day -1 (as deemed by the investigator). * Serum ferritin of \< 30 nanograms per milliliter (ng/mL) or \> 300 ng/mL for assigned male at birth (AMAB) subjects or \<16 ng/mL or \> 300 ng/mL for assigned female at birth (AFAB) subjects at Screening or Day -1. * Hemoglobin \< 13 grams per deciliter (g/dL) (8.1 millimoles per liter \[mmol/L\]) for AMAB subjects or 12 g/dL (7.5 mmol/L) for AFAB subjects at Screening or Day -1. * Blood draw or donation of blood (\>= 450 mL) within 3 months before Screening, plasma from 2 weeks before Screening, or platelets from 6 weeks before Screening.

Locations (1)

Investigator Site 82600083

Leeds, West Yorkshire, United Kingdom

Outcomes

Primary Outcomes

Plasma concentration-time course profiles of vamifeport

Time frame: Treatment Period (TP) 2: Before and after dosing on Day 4 (up to 12 hours), Day 8 (up to 48 hours), Before dosing on Day 5, 6, 7 TP 3: Before and after dosing on Day 13 (up to 48 hours) TP 4: Before and after dosing on Day 16 (up to 48 hours)

Maximum plasma concentration (Cmax) of first and last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP2: Before, and up to 48 hours after, both the first and the last dose

Time to reach Cmax (Tmax) of first and last dose vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after, both the first and the last dose

Area under the plasma concentration curve from time zero to 12 hours (AUC0-12) of first and last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after, both the first and the last dose

Trough concentration (Ctrough) of first dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: Before and up to 24 hours after the first dose in TP2

AUC from time zero to infinity (AUC0-inf) of last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after last dose

AUC from time zero to time tlast (AUC0-last) of last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after last dose

AUC from time zero to 8 hours (AUC0-8) and 24 hours (AUC0-24) of last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 8 and 24 hours after last dose

Data from ClinicalTrials.gov

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Plasma concentration at 12 hours (Conc [t=12]) of last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before and up to 12 hours after last dose

Apparent clearance (CL/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after last dose

Apparent volume of distribution at steady state (Vss/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after last dose

Accumulation ratio (Rac) of Cmax between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after first and last dose

Rac(Ctrough/Conc[t=12]) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 12 hours after first and last dose

Rac (AUC0-12) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 12 hours after first and last dose

Half-life (t1/2) after last dose of vamifeport PR1 and PR2 in Treatment Period 2

Time frame: TP 2: Before, and up to 48 hours after last dose

Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

AUC0-last of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

AUC0-8, AUC0-12 and AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4

Plasma Concentration at 8 hours (Conc [t=8]), 12 hours (Conc [t=12]) and 24 hours (Conc [t=24]) of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4

CL/F of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

t1/2 of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

Apparent volume of distribution (Vz/F) of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

Secondary Outcomes

Number of participants with treatment-emergent (TE): adverse event (AE), AE by severity, AE related to vamifeport, and serious AE

Time frame: Up to 25 days after treatment

Percentage of participants with TEAE, AE by severity, AE related to vamifeport, and serious AE

Time frame: Up to 25 days after treatment

Number of participants with clinically significant change from Baseline in clinical laboratory safety tests, 12 lead Electrocardiogram (ECG), and vital signs

The clinical laboratory safety tests include biochemistry, hematology, urinalysis.

Time frame: At baseline and up to 25 days after treatment

AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Comparison of AUC0-24 between PR1 and PR2

Time frame: Before and up to 24 hours after dosing, in TP3 and TP4

AUC0-12 of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Comparison of AUC0-12 between PR1 and PR2

Time frame: Before and up to 12 hours after dosing, in TP3 and TP4

AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Comparison of AUC0-inf between PR1 and PR2

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

Conc (t=12) of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Comparison of conc(t=12) between PR1 and PR2

Time frame: Before and up to 12 hours after dosing, in TP3 and TP4

Conc (t=24) of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Comparison of conc(t=24) between PR1 and PR2

Time frame: Before and up to 24 hours after dosing, in TP3 and TP4

Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Comparison of cmax between PR1 and PR2

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4

Comparison of tmax between PR1 and PR2

Time frame: Before and up to 48 hours after dosing, in TP3 and TP4

Absolute values of serum iron