pseudoxanthoma elasticum tissue-nonspecific alkaline phosphatase (TNAP) inhibition
Conditions
Interventions
The study drugs for this study are:
• DS-1211b film-coated tablet in 20-mg dose strength for study dose levels of
20 mg,40 mg, and 60 mg
• Matching placebo tablets
Sponsors
Daiichi Sankyo, Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Sign and date the ICF prior to the start of any study-specific qualification procedures. 2. Are male or female participants aged 18 to 75 years at screening. 3. Have an established diagnosis of PXE, with typical ocular and dermatological clinical features: a. Ocular findings - angioid streaks or peau d*orange b. Skin findings - characteristic PXE papules and plaques or diagnostic histopathological changes in lesional skin 4. Are fully vaccinated for coronavirus disease 2019 (COVID-19) per current Center for Disease Control and Prevention guidelines 5. For women of childbearing potential (not postmenopausal as a result of either natural or postsurgery cessation of menses), must have a negative serum pregnancy test at screening and must be willing to use an effective method of birth control, as detailed in Section 17.1.2 of the protocol upon entering study screening, during the treatment period, and up until the time of the follow-up visit. 6. Are willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
Exclusion criteria
Exclusion criteria: 1. Have a history of bone fracture in the past 6 months. 2. Have a history of active metabolic bone disease that significantly affect the interpretation of study biomarker results, excluding osteopenia or osteoporosis without fragility fracture. 3. Have a history of calcium pyrophosphate deposit disease such as chondrocalcinosis, pseudogout, and pyrophosphate arthropathy. 4. Have a history of hypophosphatasia. 5. Have a history of untreated hyperparathyroidism. 6. Participated in another interventional research study in the past 60 days. 7. Are participating or have participated within the last 12 months in PXE trials (eg, trials with PPi, PPi analogues such as bisphosphonate, or ENPP1 and its analogues) or in clinical trials relating to bone mineralization.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety parameters: Incidence of adverse events(AEs), including serious adverse events (SAEs), and treatment-emergent AEs, physical examination/assessment findings including vital sign measurements, standard clinical laboratory parameters, and electrocardiograms. | — |
Secondary
| Measure | Time frame |
|---|---|
| PD endpoints: AProfiles of ALP, inorganic pyrophosphate (PPi), and pyridoxal 5*- phosphate (PLP) PK endpoints: Plasma concentration and PK parameters of DS-1211a Include, but are not limited to, maximum plasma concentration, time to reach maximum plasma concentration, trough plasma concentration, area under the plasma concentration-time curve during dosing interval, area under the plasma concentration-time curve up to the last uantifiable time, and area under the plasma concentration-time curve up to infinity (if possible to calculate). | — |
Countries
Netherlands
Outcome results
None listed