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.

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.

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Demographics and baseline characteristics were assessed in the Intent-to-Treat Analysis Set.

Treatment-emergent adverse events were collected from the time of signing the informed consent form up to 14 (±5) days after the last dose of study medication, up to 98 days.