A Phase 2, 12-Week, Randomized, Double-Blind, Placebo-Controlled Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 7
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b
研究概览
简要总结
This study was designed to evaluate the safety, tolerability, pharmacodynamics (PD) of DS-1211b, and pharmacokinetics (PK) in individuals with Pseudoxanthoma elasticum (PXE). PXE is a rare disease that is associated with significant risks of visual impairments and comorbidity from peripheral and cardiovascular diseases, and adversely impacts the quality of life in afflicted individuals.
详细描述
DS-1211b, a potent small-molecule inhibitor of tissue-nonspecific alkaline phosphatase, is being developed for the treatment ectopic calcification diseases such as PXE. This study will assess DS-1211b (low-, middle-, and high-dose tablets) administered once daily for 12 weeks in individuals with PXE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated informed consent
- •Male or female participants aged 18 to 75 years at screening
- •Have an established diagnosis of PXE
- •Fully vaccinated for coronavirus disease 2019 (COVID-19) per current Center for Disease Control and Prevention guidelines
排除标准
- •Have a history of bone fracture in the past 6 months
- •Have a history of active metabolic bone disease, excluding osteopenia or osteoporosis without fragility fracture
- •Have a history of calcium pyrophosphate deposit disease
- •Have a history of hypophosphatasia
- •Have a history of untreated hyperparathyroidism
- •Participated in another interventional research study in the past 60 days.
- •Used bisphosphonate in the preceding 12 months or had plans to use bisphosphonate during the study.
- •Received Vitamin B6 supplementation >5 mg/day in the month prior to screening and during the study
- •Initiated or changed dose of Vitamin D in the preceding month prior to screening
- •Have an alkaline phosphatase <lower limit of normal (LLN) range
- •Have a QTcF interval duration >450 ms at screening
- •Have moderate to severe renal insufficiency
- •Are pregnant or breast-feeding women
- •Are female participants unwilling to use contraceptive methods
- •Have any elective surgery planned during the study period
- •Have any other significant condition (medical, psychiatric, social, or medication) that, in the judgment of the Investigator, would prevent full participation or would be inappropriate for the study
研究组 & 干预措施
DS-1211b low dose
Participants who will be randomized to receive a DS-1211 tablet once daily for 12 weeks.
干预措施: DS-1211b (Drug)
DS-1211b middle dose
Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.
干预措施: DS-1211b (Drug)
DS-1211b high dose
Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.
干预措施: DS-1211b (Drug)
Placebo
Participants who will be randomized to receive a placebo tablet once daily for 12 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b
时间窗: From the date of signing informed consent form up to Day 98 (14 days after last dose of study drug) post-dose of 12-week treatment period
TEAEs are defined as events that start on or after the first dose of study drug or start prior to but then worsen after the first dose of study drug. Adverse events are coded using MedDRA version 26.1.
Percent Change From Baseline in Pharmacodynamic Parameter Alkaline Phosphatase (ALP) Levels
时间窗: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period
ALP levels were assessed using the IFCC serum assay.
Percent Change From Baseline in Pharmacodynamic Parameter Inorganic Pyrophosphate (PPi) Levels
时间窗: Pre-dose on Days 15, 43, and 84 of 12-week treatment period
PPi levels were assessed from collected plasma.
Percent Change From Baseline in Pharmacodynamic Parameter Pyridoxal 5'-Phosphate (PLP) Levels
时间窗: Pre-dose on Days 15, 43, 84; Day 86-88 and Day 98 of 12-week treatment period
PLP levels were assessed from collected plasma.
次要结局
- Pharmacokinetic Parameter Maximum Concentration (Cmax)(Day1 and Day 84 post-dose of 12-week treatment period)
- Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)(Day 1 and Day 84 post-dose of 12-week treatment period)
- Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough)(Day 1 and Day 84 post-dose of 12-week treatment period)
- Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC)(Day 1 and Day 84 post-dose of 12-week treatment period)