Oral Pyrophosphate Absorption in PXE Disease

• ClinicalTrials.gov Identifier: NCT04441671
• Recruitment Status: Withdrawn
• First Posted: June 22, 2020
• Last Update Posted: April 22, 2021
• Sponsor: Tampere University Hospital
• Collaborators: UMC Utrecht; Hungarian Academy of Sciences
• Information provided by (Responsible Party): Tampere University Hospital

Tracking Information

• First Submitted Date: January 20, 2020
• First Posted Date: June 22, 2020
• Last Update Posted Date: April 22, 2021
• Actual Study Start Date: December 8, 2020
• Actual Primary Completion Date: April 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2021)

• 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

Original Primary Outcome Measures (submitted: June 18, 2020)

Absorption pharmacokinetics of pyrophosphate (PPi) [ Time Frame: two days ]

AUC0-t

Current Secondary Outcome Measures (submitted: April 21, 2021)

• Concentration area under the curve 0-t of phosphate [ Time Frame: two days ]
  AUC0-t
• Maximal concentration of phosphate [ Time Frame: two days ]
  Cmax
• Timepoint of maximal phosphate concentration [ Time Frame: two days ]
  Tmax

Original Secondary Outcome Measures (submitted: June 18, 2020)

• Absorption pharmacokinetics of pyrophosphate (PPi) [ Time Frame: two days ]
  Cmax
• Absorption pharmacokinetics of pyrophosphate (PPi) [ Time Frame: two days ]
  Tmax
• Absorption pharmacokinetics of phosphate (Pi) [ Time Frame: two days ]
  AUC0-t
• Absorption pharmacokinetics of phosphate (Pi) [ Time Frame: two days ]
  Cmax
• Absorption pharmacokinetics of phosphate (Pi) [ Time Frame: two days ]
  Tmax

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Oral Pyrophosphate Absorption in PXE Disease
• Official Title: Oral Disodiumpyrophosphate (Na2H2PPi) Absorption in Pseudoxanthoma Elasticum (PXE)
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pseudoxanthoma Elasticum

Intervention

Drug: Disodium Pyrophosphate

Absorption trial

Other Name: Na2H2PPi

Study Arms

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

Intervention: Drug: Disodium Pyrophosphate

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: April 21, 2021): 0
• Original Estimated Enrollment (submitted: June 18, 2020): 12
• Actual Study Completion Date: April 1, 2021
• Actual Primary Completion Date: April 1, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04441671
• Other Study ID Numbers: R19017M; 2019-002109-24 ( EudraCT Number ); KLnro 38/2019 ( Other Identifier: Fimea )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Only anonymized data can be shared

• Current Responsible Party: Tampere University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Tampere University Hospital
• Original Study Sponsor: Same as current

Collaborators

• UMC Utrecht
• Hungarian Academy of Sciences

Investigators

• Principal Investigator: Pasi I Nevalainen, MD, PhD; Tampere University Hospital

• PRS Account: Tampere University Hospital
• Verification Date: April 2021