Clinical trial NCT06726863: Pharmacokinetics and Pharmacodynamics of Two Prolonged-release Formulations of Vamifeport in Healthy Adults
Official title: A Phase 1, Randomized, Open-label Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Vamifeport After Multiple Oral Administration of One Immediate-release Formulation and After Single and Multiple Oral Administration of Two Prolonged-release Formulations in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Oral ferroportin inhibitor
Ferroportin transporter
Iron overload
Iron metabolism
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2024-12-10
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a 4-treatment period study that uses three different models: Treatment Period 1 will be a single-arm model, Treatment Period 2 will be a parallel-group model, and Treatment Periods 3 and 4 will be crossover models.
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Plasma concentration-time course profiles of vamifeport
timeFrame: 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)
measure: Maximum plasma concentration (Cmax) of first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP2: Before, and up to 48 hours after, both the first and the last dose
measure: Time to reach Cmax (Tmax) of first and last dose vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 48 hours after, both the first and the last dose
measure: 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
timeFrame: TP 2: Before, and up to 48 hours after, both the first and the last dose
measure: Trough concentration (Ctrough) of first dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: Before and up to 24 hours after the first dose in TP2
measure: AUC from time zero to infinity (AUC0-inf) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 48 hours after last dose
measure: AUC from time zero to time tlast (AUC0-last) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 48 hours after last dose
measure: 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
timeFrame: TP 2: Before, and up to 8 and 24 hours after last dose
measure: Plasma concentration at 12 hours (Conc [t=12]) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before and up to 12 hours after last dose
measure: Apparent clearance (CL/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 48 hours after last dose
measure: Apparent volume of distribution at steady state (Vss/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 48 hours after last dose
measure: Accumulation ratio (Rac) of Cmax between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 48 hours after first and last dose
measure: Rac(Ctrough/Conc[t=12]) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 12 hours after first and last dose
measure: Rac (AUC0-12) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 12 hours after first and last dose
measure: Half-life (t1/2) after last dose of vamifeport PR1 and PR2 in Treatment Period 2
timeFrame: TP 2: Before, and up to 48 hours after last dose
measure: Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: AUC0-last of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: AUC0-8, AUC0-12 and AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4
measure: 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
timeFrame: Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4
measure: CL/F of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: t1/2 of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: Apparent volume of distribution (Vz/F) of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
Secondary outcomes:
measure: Number of participants with treatment-emergent (TE): adverse event (AE), AE by severity, AE related to vamifeport, and serious AE
timeFrame: Up to 25 days after treatment
measure: Percentage of participants with TEAE, AE by severity, AE related to vamifeport, and serious AE
timeFrame: Up to 25 days after treatment
measure: Number of participants with clinically significant change from Baseline in clinical laboratory safety tests, 12 lead Electrocardiogram (ECG), and vital signs
timeFrame: At baseline and up to 25 days after treatment
measure: AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 24 hours after dosing, in TP3 and TP4
measure: AUC0-12 of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 12 hours after dosing, in TP3 and TP4
measure: AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: Conc (t=12) of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 12 hours after dosing, in TP3 and TP4
measure: Conc (t=24) of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 24 hours after dosing, in TP3 and TP4
measure: Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4
timeFrame: Before and up to 48 hours after dosing, in TP3 and TP4
measure: Absolute values of serum iron
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Absolute values of transferrin saturation (TSAT)
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Change from baseline of serum iron
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Change from baseline of TSAT
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Maximum percentage change from baseline (Emax) of serum iron
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Emax of TSAT
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Time to Emax (TEmax) of serum iron
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: TEmax of TSAT
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Time below baseline of serum iron
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: Time below baseline of TSAT
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: AUC below baseline of serum iron
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
measure: AUC below baseline of TSAT
timeFrame: Before and up to 48 hours after dosing in TP2, TP3 and TP4
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Investigator Site 82600083
state: West Yorkshire
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: