Oral Pyrophosphate Absorption in PXE Disease

Oral Disodiumpyrophosphate (Na2H2PPi) Absorption in Pseudoxanthoma Elasticum (PXE)

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.

Study Overview

• Status: Withdrawn
• Conditions: Pseudoxanthoma Elasticum
• Intervention / Treatment: Drug: Disodium Pyrophosphate

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 Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Disodium Pyrophosphate; Absorption trial; 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

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Collaborators: UMC Utrecht; Hungarian Academy of Sciences
• Investigators: Principal Investigator: Pasi I Nevalainen, MD, PhD, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: January 20, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Pseudoxanthoma Elasticum
• Other Study ID Numbers: R19017M; 2019-002109-24 (EudraCT Number); KLnro 38/2019 (Other Identifier: Fimea)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Only anonymized data can be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No