<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/NCT02212431</url>
  </required_header>
  <id_info>
    <org_study_id>3/001/14</org_study_id>
    <secondary_id>2014-000284-40</secondary_id>
    <nct_id>NCT02212431</nct_id>
  </id_info>
  <brief_title>First Study of Oral Cysteamine in Cystic Fibrosis</brief_title>
  <official_title>An Open Label Investigation of the Tolerability and Pharmacokinetics of Oral Cysteamine in Adults With Cystic Fibrosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aberdeen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cystic Fibrosis Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NHS Grampian</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Huddersfield</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aberdeen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The morbidity and mortality associated with Cystic Fibrosis (CF) are the result of chronic&#xD;
      suppurative lung disease. The aggressive use of antibiotics is one of the mainstays of&#xD;
      treatment in CF, however, the problems of multiple drug resistance and adverse reactions are&#xD;
      major clinical issues.&#xD;
&#xD;
      Cysteamine is a licensed drug used in the treatment of cystinosis. In vitro work suggests&#xD;
      that cysteamine has properties of potential benefit in CF. Cysteamine is a potent mucolytic,&#xD;
      it disrupts biofilms, it is antimicrobial, and synergises with other antibiotic agents. CF is&#xD;
      characterised by malabsorption and it is not known whether cysteamine is absorbed in CF,&#xD;
      furthermore it is not known if cysteamine enters the bronchial secretions. It is not possible&#xD;
      to assume that the pharmacokinetics of cysteamine in patients with CF are the same as those&#xD;
      reported for cystinosis.&#xD;
&#xD;
      Objectives: to characterise the pharmacokinetic profile of cysteamine in people with CF, to&#xD;
      ascertain whether cysteamine enters the bronchial secretions and the tolerability of&#xD;
      cysteamine by patients with CF.&#xD;
&#xD;
      Method: a single centre, single group open label investigation of the tolerability and&#xD;
      pharmacokinetics of oral cysteamine (Cystagon) when administered to patients with Cystic&#xD;
      Fibrosis at the dose licensed for use in cystinosis.&#xD;
&#xD;
      Setting: adult CF clinic, Aberdeen Royal Infirmary.&#xD;
&#xD;
      Target population: 12 patients aged ≥18years with CF associated lung disease who are&#xD;
      clinically stable.&#xD;
&#xD;
      Intervention: Oral cysteamine (Cystagon) will be increased from 450mg od to 450mg qds over&#xD;
      three weeks, they will remain on 450mg qds for two weeks.&#xD;
&#xD;
      Assessment: face to face health outcome assessments will be carried out for all participants&#xD;
      at recruitment/baseline, 1, 2, 3, and 5 and 6 weeks. Serial blood cysteamine levels will be&#xD;
      measured in the first 24 hours after the first dose. Sputum cysteamine will be quantified&#xD;
      after two weeks of full dose cysteamine 450mg qds. Disease specific health status (CFQ-R)&#xD;
      will be assessed at baseline and after two weeks of full dose. At each assessment, lung&#xD;
      function (FEV1, FVC), adverse reactions and serious adverse events will be ascertained. Blood&#xD;
      samples will be taken for measurement of haematological and biochemical parameters. Sputum&#xD;
      samples at each assessment will be analysed for microbial load and spinnbarkeit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cystic Fibrosis (CF) is the commonest fatal inherited disease in Caucasian populations of&#xD;
      European origin. The morbidity and mortality associated with CF are the result of chronic&#xD;
      suppurative lung disease. The lungs of people with CF are chronically infected with bacteria&#xD;
      that cause chronic infection and acute periods of worsening infection known as exacerbations.&#xD;
      Many of the bacteria that infect patients with CF are intrinsically resistant to many&#xD;
      antibiotics and bacterial antibiotic resistance is increasing, in addition many of the&#xD;
      pathogenic bacteria grow in biofilms that contributes to antibiotic resistance. The&#xD;
      aggressive use of antibiotics to suppress chronic infection and to treat acute exacerbations&#xD;
      is one of the mainstays of treatment in CF that has contributed to the increased survival of&#xD;
      CF patients. However, the problems of multiple drug resistance and adverse reactions are&#xD;
      major clinical issues. This has led to calls for research into new antibiotics and new&#xD;
      antibiotic strategies to target the biofilm and to increase the effectiveness of currently&#xD;
      available antibiotics.&#xD;
&#xD;
      Cysteamine is a licensed drug used in the treatment of cystinosis for more than 20 years.&#xD;
      Laboratory based work suggests that cysteamine may be a beneficial adjunct to conventional&#xD;
      antibiotic treatment in CF. Cysteamine is a potent mucolytic, it disrupts biofilms, it is&#xD;
      antimicrobial, and synergises with other antibiotic agents, broadening their spectrum of&#xD;
      activity, delivers a post-antimicrobial effect and reverses antibiotic resistance (even in&#xD;
      multi-drug resistant bacteria). Although the pharmacokinetic characteristics of cysteamine&#xD;
      are well established in people with cystinosis, there are no such data for cysteamine in CF.&#xD;
      CF is characterised by malabsorption and it is not known whether cysteamine is absorbed in&#xD;
      CF, furthermore it is not known if cysteamine enters the bronchial secretions. It is not&#xD;
      possible to assume that the pharmacokinetics of cysteamine in patients with CF are the same&#xD;
      as those reported for cystinosis.&#xD;
&#xD;
      Hypothesis: Oral cysteamine will be absorbed into the vascular space and bronchial secretions&#xD;
      after administration to people with Cystic Fibrosis.&#xD;
&#xD;
      Objectives: to characterise the pharmacokinetic profile of cysteamine in people with CF, to&#xD;
      ascertain whether cysteamine enters the bronchial secretions and the tolerability of&#xD;
      cysteamine by patients with CF.&#xD;
&#xD;
      Method: a single centre, single group open label investigation of the tolerability and&#xD;
      pharmacokinetics of oral cysteamine (Cystagon) when administered to patients with Cystic&#xD;
      Fibrosis at the dose licensed for use in cystinosis.&#xD;
&#xD;
      Setting: adult CF clinic, Aberdeen Royal Infirmary.&#xD;
&#xD;
      Target population: 12 patients aged ≥18years with CF associated lung disease who are&#xD;
      clinically stable.&#xD;
&#xD;
      Intervention: as recommended for cystinosis, patients will be maintained on their normal CF&#xD;
      medication. Oral cysteamine (Cystagon) will be increased from 450mg od to 450mg qds over&#xD;
      three weeks, they will remain on 450mg qds for two weeks.&#xD;
&#xD;
      Assessment: face to face health outcome assessments will be carried out for all participants&#xD;
      at recruitment/baseline, 1, 2, 3, and 5 and 6 weeks. Serial blood cysteamine levels will be&#xD;
      measured in the first 24 hours after the first dose. Sputum cysteamine will be quantified&#xD;
      after two weeks of full dose cysteamine 450mg qds. Disease specific health status (CFQ-R)&#xD;
      will be assessed at baseline and after two weeks of full dose. At each assessment, lung&#xD;
      function (FEV1, FVC), adverse reactions and serious adverse events will be ascertained. Blood&#xD;
      samples will be taken for measurement of haematological and biochemical parameters that are&#xD;
      recognised, but rare side effects of cysteamine. Sputum samples at each assessment will be&#xD;
      analysed microbiologically (quantitative, antibiotic sensitivity and rheology) to assess&#xD;
      effects of cysteamine on sputum microbiology, sputum collected prior to first dosing will be&#xD;
      used to develop a laboratory based method to quantify cysteamine in sputum.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 1/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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Elimination rate constant [k]</measure>
    <time_frame>24 hours</time_frame>
    <description>Blood cysteamine prior to the initial dose on day 1 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours post-dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration of cysteamine in sputum at week 5</measure>
    <time_frame>3 hours after final dose</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in weight from baseline at week 5</measure>
    <time_frame>5 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants with Serious and Non-Serious Adverse Events</measure>
    <time_frame>6 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in FEV1, FVC from baseline at week 5</measure>
    <time_frame>5 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in disease related health status from baseline at week 5 measured by CFQ-R</measure>
    <time_frame>5 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in haematological and biochemical indices from baseline at week 5</measure>
    <time_frame>5 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>change in sputum microbiology from baseline at week 5</measure>
    <time_frame>5 weeks</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Cysteamine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dosing will be in accordance with licensed use of cysteamine for cystinosis, i.e. 450mg qds.&#xD;
Dose will be escalated:&#xD;
450mg od for one week 450mg bd for one week 450mg tds for one week 450mg qds for two weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cysteamine</intervention_name>
    <description>Dose will be increased weekly from 450mg od to 450mg bd, to 450mg tds to 450mg qds, will remain on highest dose for 2 weeks</description>
    <arm_group_label>Cysteamine</arm_group_label>
    <other_name>Cystagon 150mg capsules</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CF related suppurative lung disease who expectorate sputum,&#xD;
&#xD;
          -  Clinically stable for &gt;4 weeks,&#xD;
&#xD;
          -  Aged ≥18 years,&#xD;
&#xD;
          -  Weight &gt;50kg,&#xD;
&#xD;
          -  Female participants of child bearing potential should be using a reliable form of&#xD;
             contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to the active substance, any form of cysteamine, or to any of the&#xD;
             excipients.&#xD;
&#xD;
          -  Hypersensitivity to penicillamine.&#xD;
&#xD;
          -  Lung, liver transplant, on active transplant list.&#xD;
&#xD;
          -  For women, current pregnancy or breast-feeding, or planned pregnancy during the study.&#xD;
&#xD;
          -  Any other significant disease/disorder which, in the investigator's opinion, either&#xD;
             puts the patient at risk because of study participation or may influence the results&#xD;
             of the study or the patient's ability to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Graham Devereux, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Aberdeen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aberdeen Royal Infirmary</name>
      <address>
        <city>Aberdeen</city>
        <zip>AB25 2ZN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>November 4, 2015</last_update_submitted>
  <last_update_submitted_qc>November 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 5, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cystic Fibrosis</keyword>
  <keyword>Cysteamine</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cysteamine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02212431
org study id: 3/001/14
secondary id: 2014-000284-40
nct id: NCT02212431
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The morbidity and mortality associated with Cystic Fibrosis (CF) are the result of chronic
      suppurative lung disease. The aggressive use of antibiotics is one of the mainstays of
      treatment in CF, however, the problems of multiple drug resistance and adverse reactions are
      major clinical issues.

      Cysteamine is a licensed drug used in the treatment of cystinosis. In vitro work suggests
      that cysteamine has properties of potential benefit in CF. Cysteamine is a potent mucolytic,
      it disrupts biofilms, it is antimicrobial, and synergises with other antibiotic agents. CF is
      characterised by malabsorption and it is not known whether cysteamine is absorbed in CF,
      furthermore it is not known if cysteamine enters the bronchial secretions. It is not possible
      to assume that the pharmacokinetics of cysteamine in patients with CF are the same as those
      reported for cystinosis.

      Objectives: to characterise the pharmacokinetic profile of cysteamine in people with CF, to
      ascertain whether cysteamine enters the bronchial secretions and the tolerability of
      cysteamine by patients with CF.

      Method: a single centre, single group open label investigation of the tolerability and
      pharmacokinetics of oral cysteamine (Cystagon) when administered to patients with Cystic
      Fibrosis at the dose licensed for use in cystinosis.

      Setting: adult CF clinic, Aberdeen Royal Infirmary.

      Target population: 12 patients aged ≥18years with CF associated lung disease who are
      clinically stable.

      Intervention: Oral cysteamine (Cystagon) will be increased from 450mg od to 450mg qds over
      three weeks, they will remain on 450mg qds for two weeks.

      Assessment: face to face health outcome assessments will be carried out for all participants
      at recruitment/baseline, 1, 2, 3, and 5 and 6 weeks. Serial blood cysteamine levels will be
      measured in the first 24 hours after the first dose. Sputum cysteamine will be quantified
      after two weeks of full dose cysteamine 450mg qds. Disease specific health status (CFQ-R)
      will be assessed at baseline and after two weeks of full dose. At each assessment, lung
      function (FEV1, FVC), adverse reactions and serious adverse events will be ascertained. Blood
      samples will be taken for measurement of haematological and biochemical parameters. Sputum
      samples at each assessment will be analysed for microbial load and spinnbarkeit.
Cystic Fibrosis (CF) is the commonest fatal inherited disease in Caucasian populations of
      European origin. The morbidity and mortality associated with CF are the result of chronic
      suppurative lung disease. The lungs of people with CF are chronically infected with bacteria
      that cause chronic infection and acute periods of worsening infection known as exacerbations.
      Many of the bacteria that infect patients with CF are intrinsically resistant to many
      antibiotics and bacterial antibiotic resistance is increasing, in addition many of the
      pathogenic bacteria grow in biofilms that contributes to antibiotic resistance. The
      aggressive use of antibiotics to suppress chronic infection and to treat acute exacerbations
      is one of the mainstays of treatment in CF that has contributed to the increased survival of
      CF patients. However, the problems of multiple drug resistance and adverse reactions are
      major clinical issues. This has led to calls for research into new antibiotics and new
      antibiotic strategies to target the biofilm and to increase the effectiveness of currently
      available antibiotics.

      Cysteamine is a licensed drug used in the treatment of cystinosis for more than 20 years.
      Laboratory based work suggests that cysteamine may be a beneficial adjunct to conventional
      antibiotic treatment in CF. Cysteamine is a potent mucolytic, it disrupts biofilms, it is
      antimicrobial, and synergises with other antibiotic agents, broadening their spectrum of
      activity, delivers a post-antimicrobial effect and reverses antibiotic resistance (even in
      multi-drug resistant bacteria). Although the pharmacokinetic characteristics of cysteamine
      are well established in people with cystinosis, there are no such data for cysteamine in CF.
      CF is characterised by malabsorption and it is not known whether cysteamine is absorbed in
      CF, furthermore it is not known if cysteamine enters the bronchial secretions. It is not
      possible to assume that the pharmacokinetics of cysteamine in patients with CF are the same
      as those reported for cystinosis.

      Hypothesis: Oral cysteamine will be absorbed into the vascular space and bronchial secretions
      after administration to people with Cystic Fibrosis.

      Objectives: to characterise the pharmacokinetic profile of cysteamine in people with CF, to
      ascertain whether cysteamine enters the bronchial secretions and the tolerability of
      cysteamine by patients with CF.

      Method: a single centre, single group open label investigation of the tolerability and
      pharmacokinetics of oral cysteamine (Cystagon) when administered to patients with Cystic
      Fibrosis at the dose licensed for use in cystinosis.

      Setting: adult CF clinic, Aberdeen Royal Infirmary.

      Target population: 12 patients aged ≥18years with CF associated lung disease who are
      clinically stable.

      Intervention: as recommended for cystinosis, patients will be maintained on their normal CF
      medication. Oral cysteamine (Cystagon) will be increased from 450mg od to 450mg qds over
      three weeks, they will remain on 450mg qds for two weeks.

      Assessment: face to face health outcome assessments will be carried out for all participants
      at recruitment/baseline, 1, 2, 3, and 5 and 6 weeks. Serial blood cysteamine levels will be
      measured in the first 24 hours after the first dose. Sputum cysteamine will be quantified
      after two weeks of full dose cysteamine 450mg qds. Disease specific health status (CFQ-R)
      will be assessed at baseline and after two weeks of full dose. At each assessment, lung
      function (FEV1, FVC), adverse reactions and serious adverse events will be ascertained. Blood
      samples will be taken for measurement of haematological and biochemical parameters that are
      recognised, but rare side effects of cysteamine. Sputum samples at each assessment will be
      analysed microbiologically (quantitative, antibiotic sensitivity and rheology) to assess
      effects of cysteamine on sputum microbiology, sputum collected prior to first dosing will be
      used to develop a laboratory based method to quantify cysteamine in sputum.
allocation: N/A
intervention model: Single Group Assignment
masking: None (Open Label)
measure: Elimination rate constant [k]
time frame: 24 hours
description: Blood cysteamine prior to the initial dose on day 1 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 hours post-dose
measure: Concentration of cysteamine in sputum at week 5
time frame: 3 hours after final dose
measure: Change in weight from baseline at week 5
time frame: 5 weeks
measure: Number of Participants with Serious and Non-Serious Adverse Events
time frame: 6 weeks
measure: Change in FEV1, FVC from baseline at week 5
time frame: 5 weeks
measure: Change in disease related health status from baseline at week 5 measured by CFQ-R
time frame: 5 weeks
measure: Change in haematological and biochemical indices from baseline at week 5
time frame: 5 weeks
measure: change in sputum microbiology from baseline at week 5
time frame: 5 weeks
arm group label: Cysteamine
arm group type: Experimental
description: Dosing will be in accordance with licensed use of cysteamine for cystinosis, i.e. 450mg qds.
Dose will be escalated:
450mg od for one week 450mg bd for one week 450mg tds for one week 450mg qds for two weeks
intervention type: Drug
intervention name: Cysteamine
description: Dose will be increased weekly from 450mg od to 450mg bd, to 450mg tds to 450mg qds, will remain on highest dose for 2 weeks
arm group label: Cysteamine
other name: Cystagon 150mg capsules
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Graham Devereux, MD
role: Principal Investigator
affiliation: University of Aberdeen
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Cysteamine