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

Phase 1

Not yet recruiting

• Conditions: Healthy Volunteers
• Interventions: Drug: Vamifeport PR2; Drug: Vamifeport IRF; Drug: Vamifeport PR1

• Registration Number: NCT06726863
• Lead Sponsor: CSL Behring

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-06
• Study First Submitted QC: 2024-12-06
• Last Update Submitted: 2024-12-06
• Study First Posted: 2024-12-10
• Last Update Posted: 2024-12-10
• Study Start: 2024-12-11
• Primary Completion: 2025-01-27
• Study Completion: 2025-02-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 22

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Period 4: Vamifeport PR2 Dose Level 3	Vamifeport PR2	Participants will receive a single dose of Vamifeport PR2 at Dose level 3.
Treatment Period 1: Vamifeport IR Formulation Dose Level 1	Vamifeport IRF	Participants will receive multiple doses of Vamifeport Immediate-release (IR) formulation at Dose level 1.
Treatment Period 2: Vamifeport PR1 Dose Level 2	Vamifeport PR1	Participants will receive multiple doses of Vamifeport Prolonged-release formulation 1 (PR1) at Dose level 2.
Treatment Period 2: Vamifeport PR2 Dose Level 2	Vamifeport PR2	Participants will receive multiple doses of Vamifeport Prolonged-release formulation 2 (PR2) at Dose level 2.
Treatment Period 3: Vamifeport PR1 Dose Level 3	Vamifeport PR1	Participants will receive a single dose of Vamifeport PR1 at Dose level 3.
Treatment Period 3: Vamifeport PR2 Dose Level 3	Vamifeport PR2	Participants will receive a single dose of Vamifeport PR2 at Dose level 3.
Treatment Period 4: Vamifeport PR1 Dose Level 3	Vamifeport PR1	Participants will receive a single dose of Vamifeport PR1 at Dose level 3.

Primary Outcome Measures

Name	Time	Method
Plasma concentration-time course profiles of vamifeport	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	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	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	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	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	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	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	TP 2: Before, and up to 8 and 24 hours after last dose
Plasma concentration at 12 hours (Conc [t=12]) of last dose of vamifeport PR1 and PR2 in Treatment Period 2	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	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	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	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	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	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	TP 2: Before, and up to 48 hours after last dose
Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4
Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	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	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	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	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	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	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	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	Before and up to 48 hours after dosing, in TP3 and TP4

Secondary Outcome Measures

Name	Time	Method
Percentage of participants with TEAE, AE by severity, AE related to vamifeport, and serious AE	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	At baseline and up to 25 days after treatment	The clinical laboratory safety tests include biochemistry, hematology, urinalysis.
Number of participants with treatment-emergent (TE): adverse event (AE), AE by severity, AE related to vamifeport, and serious AE	Up to 25 days after treatment
AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 24 hours after dosing, in TP3 and TP4	Comparison of AUC0-24 between PR1 and PR2
AUC0-12 of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 12 hours after dosing, in TP3 and TP4	Comparison of AUC0-12 between PR1 and PR2
AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4	Comparison of AUC0-inf between PR1 and PR2
Conc (t=12) of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 12 hours after dosing, in TP3 and TP4	Comparison of conc(t=12) between PR1 and PR2
Conc (t=24) of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 24 hours after dosing, in TP3 and TP4	Comparison of conc(t=24) between PR1 and PR2
Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4	Comparison of cmax between PR1 and PR2
Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4	Comparison of tmax between PR1 and PR2
Absolute values of serum iron	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Absolute values of transferrin saturation (TSAT)	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Change from baseline of serum iron	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Change from baseline of TSAT	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Maximum percentage change from baseline (Emax) of serum iron	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Emax of TSAT	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Time to Emax (TEmax) of serum iron	Before and up to 48 hours after dosing in TP2, TP3 and TP4
TEmax of TSAT	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Time below baseline of serum iron	Before and up to 48 hours after dosing in TP2, TP3 and TP4
Time below baseline of TSAT	Before and up to 48 hours after dosing in TP2, TP3 and TP4
AUC below baseline of serum iron	Before and up to 48 hours after dosing in TP2, TP3 and TP4
AUC below baseline of TSAT	Before and up to 48 hours after dosing in TP2, TP3 and TP4