An Open-label Study to Evaluate the Safety and Pharmacokinetics of Migalastat HCl in Subjects With Fabry Disease and Amenable GLA Variants and Severe Renal Impairment or End-Stage Renal Disease Treated With Hemodialysis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 14
- 试验地点
- 22
- 主要终点
- Apparent terminal elimination half-life (t½)
研究概览
简要总结
An Open-label Study to Evaluate the Safety and Pharmacokinetics of Migalastat HCl in Subjects with Fabry Disease and Amenable GLA Variants and Severe Renal Impairment (SRI) or End Stage Renal Disease (ESRD)
详细描述
This is an open-label, non-comparative study for subjects with Fabry disease who have an estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease equation (eGFRMDRD) value of < 30 mL/min/1.73 m2. Subjects may have had previous exposure to migalastat, either commercially or as a participant in a previous migalastat study.
Two distinct populations of subjects with Fabry disease and renal impairment will be enrolled into this study:
- Cohort 1: Subjects with SRI not receiving any type of dialysis treatment
- Cohort 2: ESRD subjects who are receiving hemodialysis treatment, either standard hemodialysis (HD) or hemodiafiltration (HDF). Only subjects who can receive HD/HDF at the study clinic or at an affiliated center where the Investigator already has oversight should be enrolled into Cohort 2.
Subjects entering into this study will undergo screening (Visit 1) to confirm enrollment eligibility including confirmatory GLA genotyping. Subjects who meet eligibility criteria will have a Baseline Visit (Visit 2) within 30 days of screening. Subjects who do not meet eligibility criteria (eg, subjects with an eGFR > 30 mL/min/1.73 m2) may be re-screened.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged 18 years or older, diagnosed with Fabry disease.
- •Subject (or legally authorized representative as applicable) is willing and able to provide written informed consent and authorization for use and disclosure of Personal Health Information
- •Subject has a GLA variant that is amenable to migalastat recorded in their medical records
- •Subject has at least 1 documented eGFR value of < 30 mL/min/1.73 m2 within the last 3 months and has an eGFRMDRD value of < 30 mL/min/1.73 m2 at Visit 1
- •Subjects with ESRD have been on a stable 2- or 3-times a week HD (standard or HDF) regimen for at least 2 months prior to the screening visit
- •Subjects with ESRD must commit to completing at least 4 standard HD or HDF sessions during each 2-week dosing interval.
- •Subjects with ESRD must commit to completing the entire prescribed duration for each dialysis session.
- •If of reproductive potential, both male and female patients agree to use a medically accepted method of contraception
排除标准
- •Subject has undergone kidney transplantation
- •Subject is on peritoneal dialysis
- •Subject is treated or has been treated with another investigational drug (except migalastat) within the 30 days
- •Subject has undergone any gene therapy at any time prior to the study or anticipates undergoing gene therapy during the study.
- •Subject has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction
- •Subject has clinically significant unstable cardiac disease
- •Subject has any intercurrent illness or condition that may preclude the subject from fulfilling the protocol requirements
- •Subject has a history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol)
- •Subject requires concurrent treatment with Glyset® (miglitol), Replagal® (agalsidase alfa), or Fabrazyme® (agalsidase beta)
- •Subject requires concurrent treatment with Zavesca® (miglustat) or has been treated with Zavesca
- •Female subject is pregnant or breast-feeding
- •Subject is unable to comply with study requirements
- •In France only, protected persons as defined by the Public Health Code
研究组 & 干预措施
Cohort 2: End-Stage Renal Disease
All hemodialysis subjects will receive migalastat 123 mg, equivalent to 150 mg migalastat HCl (hereafter, migalastat). Subjects will take 1 migalastat capsule orally with water every other week.
干预措施: migalastat HCl 150 mg (Drug)
Cohort 1: Severe Renal Impairment
All subjects will receive migalastat 123 mg, equivalent to 150 mg migalastat HCl (hereafter, migalastat) at a dose regimen based on their eGFRMDRD result at Visit 1. Subjects will take 1 migalastat capsule orally with water either every 4 or 7 days.
结局指标
主要结局
Apparent terminal elimination half-life (t½)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK
Concentration at the end of a dosing interval at steady state (Ctrough)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Average plasma migalastat concentration over the dosing interval (Cavg)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Area under the concentration-time curve at steady state during the dosing interval (AUC0-τ)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Area under the concentration-time curve from zero time (pre-dose) extrapolated to infinite time (AUC0-∞)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Apparent plasma clearance (CL/F)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK
Apparent terminal phase volume of distribution (Vz/F)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Dialysis clearance (CLD)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Volume of dialysate collected during the interval (VD)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Mean migalastat concentration in dialysate (CD)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Amount recovered in dialysate (AeD)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Fraction of the dose recovered in dialysate (FeD)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Mean migalastat plasma concentration during the dialysis interval (P)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Maximum observed concentration (Cmax)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Time to maximum concentration (tmax)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Mean inlet area under the curve (AUCinlet)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Mean outlet area under the curve (AUCoutlet)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Extraction ratio (ED)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Dialyzer blood flow (QD)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Cumulative amount excreted over all collection intervals (Ae0-τ)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Fraction of the dose recovered after the last measurable time point postdose (Fe0-τ)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
Renal clearance (CLr)
时间窗: Baseline through Month 12
To characterize the pharmacokinetics (PK) of migalastat and validate the population PK (popPK) model and simulations.
次要结局
- Adverse events (AEs)(Baseline through Month 12)
- Change from baseline in estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease equation (eGFR MDRD)(Baseline through Month 12)
- Change from baseline eGFR based on the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI)(Baseline through Month 12)
- Change from baseline in plasma globotriaosylsphingosine (lyso-Gb3)(Baseline through Month 12)