<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/NCT01735240</url>
  </required_header>
  <id_info>
    <org_study_id>D3550C00011</org_study_id>
    <nct_id>NCT01735240</nct_id>
  </id_info>
  <brief_title>Phase I Study to Assess the Effect on Healthy Male Volunteers of Ketoconazole on the Pharmacokinetics of a Single Dose of AZD5069 Administered Orally.</brief_title>
  <official_title>An Open-label, Fixed-sequence, Single-centre Phase I Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of AZD5069 After Oral Administration of a Single Dose AZD5069 to Healthy Male Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <brief_summary>
    <textblock>
      The main purpose of the study is to compare the change of the AZD5069 Pharmacokinetic profile&#xD;
      when administered with ketoconazole. Subjects will be treated first with AZD5069 only&#xD;
      followed by a washout period before starting with the combined treatment (both ketoconazole&#xD;
      and AZD5069).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An open-label, fixed-sequence, single-centre phase I study to assess the effect of&#xD;
      ketoconazole on the pharmacokinetics of AZD5069 after oral administration of a single dose&#xD;
      AZD5069 to healthy male volunteers&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">February 2013</completion_date>
  <primary_completion_date type="Actual">February 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of AZD5069 (15 mg) and a metabolite (AZ13587715) measured by AUC, AUC(0-t), Cmax, λz, t½λz, tmax, CL/F (AZD5069 only), Vz/F (alone and in combination with Ketoconazole)</measure>
    <time_frame>Day 1, Day 2 at 24 hours post dose and Day 3 at 48 hours post dose in period 1 and Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.</time_frame>
    <description>(AUC(0-t)) area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, (Cmax) observed maximum plasma concentration, (λz) terminal rate constant, (t½λz) terminal half-life, (tmax) time to reach maximum plasma concentration (tmax), (CL/F) apparent oral clearance (AZD5069 only), (Vz/F) apparent volume of distribution.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of Ketoconazole measured by AUC(0-t) and Cmax (in combination with AZD5069)</measure>
    <time_frame>Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Numbers of circulating neutrophil in blood measured by AZD5069 administration alone and in combination with Ketoconazole</measure>
    <time_frame>Day 1, 2, 3 at predose, 4, 8, 12, 24, 48 hours post dose in period 1 and Day 1, 2, 3, 4 at predose, 4, 8, 12, 24, 48 hours post dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of AZD5069 (15 mg) in combination with Ketoconazole by assessing a panel of adverse events measures: laboratory assessments, vital signs, physical examination and 12-led electrocardiogram.</measure>
    <time_frame>Up to 2 months</time_frame>
    <description>Measures: laboratory assessments (clinical chemistry, haematology, urinalysis), vital signs (blood pressure, pulse rate, including body temperature), physical examination and 12-led electrocardiogram.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Asthma,</condition>
  <condition>Pharmacokinetics,</condition>
  <condition>Cmax,</condition>
  <condition>Tmax,</condition>
  <condition>λz,</condition>
  <condition>AUC,</condition>
  <condition>Ketoconazole,</condition>
  <condition>Metabolite</condition>
  <arm_group>
    <arm_group_label>First AZD5069, then Ketoconazole + AZD5069</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AZD5069 in first period (on 1 day) and in second period (after wash out) ketoconazole alone (on 2 days) then ketoconazole + AZD5069 (on 1 day), then again ketoconazole alone (on 2 days)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD5069</intervention_name>
    <description>AZD5069 15 mg (3x5 mg capsules) single administration</description>
    <arm_group_label>First AZD5069, then Ketoconazole + AZD5069</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketoconazole</intervention_name>
    <description>Ketoconazole 400 mg (2x200 mg tablets)</description>
    <arm_group_label>First AZD5069, then Ketoconazole + AZD5069</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male volunteers aged 18 to 50 years (inclusive).&#xD;
&#xD;
          -  Veins suitable for cannulation or repeated venipuncture.&#xD;
&#xD;
          -  Healthy volunteers with neutrophil counts within the laboratory normal reference range&#xD;
             at Screening&#xD;
&#xD;
          -  Body mass index (BMI) ≥18.0 and ≤30.0 kg/m2 calculated from height and weight at&#xD;
             screening; minimum weight 50 kg and maximum weight 100 kg.&#xD;
&#xD;
          -  Non-smokers or ex-smokers with no smoking history for the last 3 months prior to&#xD;
             screening and a smoking history of less than 10 pack years (1 pack year = tobacco&#xD;
             consumption corresponding to 20 cigarettes smoked per day for 1 year) at screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Healthy volunteers with latent tuberculosis as suggested by their history and judged&#xD;
             by the Investigator&#xD;
&#xD;
          -  Healthy volunteers who belong to a high-risk group for HIV infection.&#xD;
&#xD;
          -  Known or suspected history of significant drug abuse as judged by the Investigator.&#xD;
&#xD;
          -  History of alcohol abuse or excessive intake of alcohol as judged by the Investigator.&#xD;
&#xD;
          -  Plasma donation within 1 month of screening or any blood donation/blood loss &gt;500 mL&#xD;
             during the 3 months and/or 1350 mL within the 12 months prior to screening.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bengt Larsson, Dr.</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca Pharmaceutical</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gillian Pilbrow</last_name>
    <role>Study Chair</role>
    <affiliation>AstraZeneca Pharmaceutical</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Leonard Siew, DR.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quintiles Drug Research Unit at Guy's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=1339&amp;filename=D3550C00011_Study_Synopsis.pdf</url>
    <description>CSR Synopsis</description>
  </link>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>June 24, 2015</last_update_submitted>
  <last_update_submitted_qc>June 24, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 25, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase I,</keyword>
  <keyword>healthy volunteers,</keyword>
  <keyword>fixed-sequence,</keyword>
  <keyword>open-label,</keyword>
  <keyword>ketoconazole,</keyword>
  <keyword>combination,</keyword>
  <keyword>safety</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketoconazole</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/NCT01735240
org study id: D3550C00011
nct id: NCT01735240
lead sponsor: 
The main purpose of the study is to compare the change of the AZD5069 Pharmacokinetic profile
      when administered with ketoconazole. Subjects will be treated first with AZD5069 only
      followed by a washout period before starting with the combined treatment (both ketoconazole
      and AZD5069).
An open-label, fixed-sequence, single-centre phase I study to assess the effect of
      ketoconazole on the pharmacokinetics of AZD5069 after oral administration of a single dose
      AZD5069 to healthy male volunteers
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Pharmacokinetics of AZD5069 (15 mg) and a metabolite (AZ13587715) measured by AUC, AUC(0-t), Cmax, λz, t½λz, tmax, CL/F (AZD5069 only), Vz/F (alone and in combination with Ketoconazole)
time frame: Day 1, Day 2 at 24 hours post dose and Day 3 at 48 hours post dose in period 1 and Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.
description: (AUC(0-t)) area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, (Cmax) observed maximum plasma concentration, (λz) terminal rate constant, (t½λz) terminal half-life, (tmax) time to reach maximum plasma concentration (tmax), (CL/F) apparent oral clearance (AZD5069 only), (Vz/F) apparent volume of distribution.
measure: Pharmacokinetics of Ketoconazole measured by AUC(0-t) and Cmax (in combination with AZD5069)
time frame: Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.
measure: Numbers of circulating neutrophil in blood measured by AZD5069 administration alone and in combination with Ketoconazole
time frame: Day 1, 2, 3 at predose, 4, 8, 12, 24, 48 hours post dose in period 1 and Day 1, 2, 3, 4 at predose, 4, 8, 12, 24, 48 hours post dose
measure: Safety of AZD5069 (15 mg) in combination with Ketoconazole by assessing a panel of adverse events measures: laboratory assessments, vital signs, physical examination and 12-led electrocardiogram.
time frame: Up to 2 months
description: Measures: laboratory assessments (clinical chemistry, haematology, urinalysis), vital signs (blood pressure, pulse rate, including body temperature), physical examination and 12-led electrocardiogram.
arm group label: First AZD5069, then Ketoconazole + AZD5069
arm group type: Experimental
description: AZD5069 in first period (on 1 day) and in second period (after wash out) ketoconazole alone (on 2 days) then ketoconazole + AZD5069 (on 1 day), then again ketoconazole alone (on 2 days)
intervention type: Drug
intervention name: AZD5069
description: AZD5069 15 mg (3x5 mg capsules) single administration
arm group label: First AZD5069, then Ketoconazole + AZD5069
intervention type: Drug
intervention name: Ketoconazole
description: Ketoconazole 400 mg (2x200 mg tablets)
arm group label: First AZD5069, then Ketoconazole + AZD5069
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bengt Larsson, Dr.
role: Study Director
affiliation: AstraZeneca Pharmaceutical
last name: Gillian Pilbrow
role: Study Chair
affiliation: AstraZeneca Pharmaceutical
last name: Leonard Siew, DR.
role: Principal Investigator
affiliation: Quintiles Drug Research Unit at Guy's Hospital
facility: 
country: United Kingdom
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1339&filename=D3550C00011_Study_Synopsis.pdf
description: CSR Synopsis
responsible party type: Sponsor
mesh term: Ketoconazole