<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04441671</url>
  </required_header>
  <id_info>
    <org_study_id>R19017M</org_study_id>
    <secondary_id>2019-002109-24</secondary_id>
    <secondary_id>KLnro 38/2019</secondary_id>
    <nct_id>NCT04441671</nct_id>
  </id_info>
  <brief_title>Oral Pyrophosphate Absorption in PXE Disease</brief_title>
  <official_title>Oral Disodiumpyrophosphate (Na2H2PPi) Absorption in Pseudoxanthoma Elasticum (PXE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tampere University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>UMC Utrecht</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hungarian Academy of Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tampere University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pyrophosphate is an endogenous, non-toxic metabolite inhibiting soft tissue calcification.&#xD;
      The aim of our study is to find optimal dosing and safety of oral disodium-PPi (Na2H2PPi).&#xD;
      Absorption curves (pharmacokinetics), AUC0-t, Cmax and Tmax for PPi and phosphate will be&#xD;
      provided for healthy controls and PXE-patients both fasting and with standard meal intake.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase II oral capsulized disodium-PPi (Na2H2PPi) powder absorption study in subjects with PXE&#xD;
      (n=8-12) will be done in the ward of Internal Medicine of Tampere University Hospital and&#xD;
      University Medical Center Utrecht.&#xD;
&#xD;
      After a 10-hour fast at 8.00 a.m. 30 mg/kg (first day) and 50 mg/kg (second day) capsulized&#xD;
      dose of PPi will be given with 2 dl water. At 12.00 a.m. another capsulized 30 mg/kg (first&#xD;
      day) or 50 mg/kg (second day) single dose of PPi with a standard mixed meal (lunch) will be&#xD;
      given with 2 dl water at the time when a subject starts eating.&#xD;
&#xD;
      Plasma and urine sampling include plasma and spot urine electrolytes, creatinine, and&#xD;
      pyrophosphate. Plasma sampling will be done at 0, 15, 30, 60, 120 and 240 min after ingestion&#xD;
      of PPi. Urine spot sample will be taken at 0 and 240 min after ingestion of PPi.&#xD;
&#xD;
      Physical activity is restricted. Side-effects will be recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Withdrawn&#xD;
  </why_stopped>
  <start_date type="Actual">December 8, 2020</start_date>
  <completion_date type="Actual">April 1, 2021</completion_date>
  <primary_completion_date type="Actual">April 1, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Concentration area under the curve 0-t of pyrophosphate</measure>
    <time_frame>two days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximal concentration of pyrophosphate</measure>
    <time_frame>two days</time_frame>
    <description>Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Timepoint of maximal pyrophosphate concentration</measure>
    <time_frame>two days</time_frame>
    <description>Tmax</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration area under the curve 0-t of phosphate</measure>
    <time_frame>two days</time_frame>
    <description>AUC0-t</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal concentration of phosphate</measure>
    <time_frame>two days</time_frame>
    <description>Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Timepoint of maximal phosphate concentration</measure>
    <time_frame>two days</time_frame>
    <description>Tmax</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pseudoxanthoma Elasticum</condition>
  <arm_group>
    <arm_group_label>Open label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Disodium Pyrophosphate</intervention_name>
    <description>Absorption trial</description>
    <arm_group_label>Open label</arm_group_label>
    <other_name>Na2H2PPi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults (&gt;18 yrs)&#xD;
&#xD;
          -  clinically and genetically proven PXE&#xD;
&#xD;
          -  Body mass index (BMI) 18,5-34,9 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Special groups according to researchers' decision.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  No effective contraception in females in child-bearing age.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pasi I Nevalainen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tampere University Hospital</affiliation>
  </overall_official>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 20, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>April 21, 2021</last_update_submitted>
  <last_update_submitted_qc>April 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pseudoxanthoma Elasticum</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Only anonymized data can be shared</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04441671
org study id: R19017M
secondary id: 2019-002109-24
secondary id: KLnro 38/2019
nct id: NCT04441671
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Concentration area under the curve 0-t of pyrophosphate
time frame: two days
measure: Maximal concentration of pyrophosphate
time frame: two days
description: Cmax
measure: Timepoint of maximal pyrophosphate concentration
time frame: two days
description: Tmax
measure: Concentration area under the curve 0-t of phosphate
time frame: two days
description: AUC0-t
measure: Maximal concentration of phosphate
time frame: two days
description: Cmax
measure: Timepoint of maximal phosphate concentration
time frame: two days
description: Tmax
arm group label: Open label
arm group type: Experimental
description: 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 type: Drug
intervention name: Disodium Pyrophosphate
description: Absorption trial
arm group label: Open label
other name: Na2H2PPi
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Pasi I Nevalainen, MD, PhD
role: Principal Investigator
affiliation: Tampere University Hospital
responsible party type: Sponsor
mesh term: Pseudoxanthoma Elasticum
sharing ipd: No
ipd description: Only anonymized data can be shared