Oral Pyrophosphate Absorption in PXE Disease

Phase 2

Withdrawn

• Conditions: Pseudoxanthoma Elasticum
• Interventions: Drug: Disodium Pyrophosphate

• Registration Number: NCT04441671
• Lead Sponsor: Tampere University Hospital

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 Timeline

• Study First Submitted: 2020-01-20
• Study First Submitted QC: 2020-06-18
• Study First Posted: 2020-06-22
• Study Start: 2020-12-08
• Status Verified: 2021-04
• Primary Completion: 2021-04-01
• Study Completion: 2021-04-01
• Last Update Submitted: 2021-04-21
• Last Update Posted: 2021-04-22

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label	Disodium Pyrophosphate	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

Primary Outcome Measures

Name	Time	Method
Concentration area under the curve 0-t of pyrophosphate	two days
Maximal concentration of pyrophosphate	two days	Cmax
Timepoint of maximal pyrophosphate concentration	two days	Tmax

Secondary Outcome Measures

Name	Time	Method
Concentration area under the curve 0-t of phosphate	two days	AUC0-t
Maximal concentration of phosphate	two days	Cmax
Timepoint of maximal phosphate concentration	two days	Tmax