A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
- Registration Number
- NCT05569252
- Lead Sponsor
- Daiichi Sankyo
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 65
- 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
Key
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DS-1211b low dose DS-1211b Participants who will be randomized to receive a DS-1211 tablet once daily for 12 weeks. DS-1211b middle dose DS-1211b Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks. Placebo Placebo Participants who will be randomized to receive a placebo tablet once daily for 12 weeks. DS-1211b high dose DS-1211b Participants who will be randomized to receive a DS-1211b tablet once daily for 12 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events (TEAEs) in Participants Receiving DS-1211b 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 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 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 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.
- Secondary Outcome Measures
Name Time Method Pharmacokinetic Parameter Maximum Concentration (Cmax) Day1 and Day 84 post-dose of 12-week treatment period Pharmacokinetic parameter Cmax was estimated using population PK modeling.
Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) Day 1 and Day 84 post-dose of 12-week treatment period Pharmacokinetic parameter Tmax was assessed using population PK modeling.
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) Day 1 and Day 84 post-dose of 12-week treatment period Pharmacokinetic parameter Ctrough was assessed using observed concentrations at 10 hours post-dose.
Pharmacokinetic Parameter Area Under the Plasma Concentration-time Curve (AUC) Day 1 and Day 84 post-dose of 12-week treatment period Pharmacokinetic parameter AUCtau was assessed using population PK modeling.
Trial Locations
- Locations (7)
UMC Utrecht
🇳🇱Utrecht, Netherlands
Clinical Research of Philadelphia, LLC
🇺🇸Philadelphia, Pennsylvania, United States
Boston Neuro Research Center
🇺🇸North Dartmouth, Massachusetts, United States
Clinilabs
🇺🇸New York, New York, United States
Mid-Atlantic Epilepsy and Sleep Center
🇺🇸Bethesda, Maryland, United States
Infinity Medical Research Inc
🇺🇸North Dartmouth, Massachusetts, United States
Frontage Clinical Services, Inc.
🇺🇸Secaucus, New Jersey, United States