Oral Disodiumpyrophosphate (Na2H2PPi) Absorption in Pseudoxanthoma Elasticum (PXE)
Overview
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Tampere University Hospital
- Primary Endpoint
- Concentration area under the curve 0-t of pyrophosphate
Overview
Brief Summary
Pyrophosphate is an endogenous, non-toxic metabolite inhibiting soft tissue calcification. The aim of our study is to find optimal dosing and safety of oral disodium-PPi (Na2H2PPi). Absorption curves (pharmacokinetics), AUC0-t, Cmax and Tmax for PPi and phosphate will be provided for healthy controls and PXE-patients both fasting and with standard meal intake.
Detailed Description
Phase II oral capsulized disodium-PPi (Na2H2PPi) powder absorption study in subjects with PXE (n=8-12) will be done in the ward of Internal Medicine of Tampere University Hospital and University Medical Center Utrecht.
After a 10-hour fast at 8.00 a.m. 30 mg/kg (first day) and 50 mg/kg (second day) capsulized dose of PPi will be given with 2 dl water. At 12.00 a.m. another capsulized 30 mg/kg (first day) or 50 mg/kg (second day) single dose of PPi with a standard mixed meal (lunch) will be given with 2 dl water at the time when a subject starts eating.
Plasma and urine sampling include plasma and spot urine electrolytes, creatinine, and pyrophosphate. Plasma sampling will be done at 0, 15, 30, 60, 120 and 240 min after ingestion of PPi. Urine spot sample will be taken at 0 and 240 min after ingestion of PPi.
Physical activity is restricted. Side-effects will be recorded.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults (\>18 yrs)
- •clinically and genetically proven PXE
- •Body mass index (BMI) 18,5-34,9 kg/m2
Exclusion Criteria
- •Special groups according to researchers' decision.
- •Pregnancy
- •No effective contraception in females in child-bearing age.
Arms & Interventions
Open label
Disodiumpyrophosphate, capsuled powder, First day: 30 mg/kg fasting at 08.00 and with standard mixed meal at 12.00 Second day: 50 mg/kg fasting at 08.00 and with standard mixed meal at 12.00
Intervention: Disodium Pyrophosphate (Drug)
Outcomes
Primary Outcomes
Concentration area under the curve 0-t of pyrophosphate
Time Frame: two days
Maximal concentration of pyrophosphate
Time Frame: two days
Cmax
Timepoint of maximal pyrophosphate concentration
Time Frame: two days
Tmax
Secondary Outcomes
- Concentration area under the curve 0-t of phosphate(two days)
- Maximal concentration of phosphate(two days)
- Timepoint of maximal phosphate concentration(two days)