Healthy Volunteers
Conditions
Keywords
Oral ferroportin inhibitor, Ferroportin transporter, Iron overload, Iron metabolism
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.
Interventions
DRUGVamifeport IRF
Vamifeport IRF will be administered orally as per the dosing levels and formulations for respective treatment periods.
DRUGVamifeport PR1
Vamifeport PR1 will be administered orally as per the dosing levels and formulations for respective treatment periods.
DRUGVamifeport PR2
Vamifeport PR2 will be administered orally as per the dosing levels and formulations for respective treatment periods.
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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-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-last of vamifeport PR1 and PR2 in Treatment Period 3 and 4 | Before and up to 48 hours after dosing, in TP3 and TP4 |
| AUC0-8, 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 | — |
| 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 | — |
Countries
United Kingdom
Outcome results
None listed