Oral Pyrophosphate Absorption in PXE Disease

Study 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.

Official Title
-----------------
Oral Disodiumpyrophosphate (Na2H2PPi) Absorption in Pseudoxanthoma Elasticum (PXE)

Conditions
-----------------
Pseudoxanthoma Elasticum

Intervention / Treatment
-----------------
* Drug: Disodium Pyrophosphate


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label<br>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 | Drug: Disodium Pyrophosphate<br>* Absorption trial<br>* Other names: Na2H2PPi;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration area under the curve 0-t of pyrophosphate |  | two days | 
| Maximal concentration of pyrophosphate | Cmax | two days | 
| Timepoint of maximal pyrophosphate concentration | Tmax | two days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration area under the curve 0-t of phosphate | AUC0-t | two days | 
| Maximal concentration of phosphate | Cmax | two days | 
| Timepoint of maximal phosphate concentration | Tmax | two days |