<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/NCT03019614</url>
  </required_header>
  <id_info>
    <org_study_id>DIUR-001</org_study_id>
    <nct_id>NCT03019614</nct_id>
  </id_info>
  <brief_title>An Open Label Study in Healthy Volunteers to Compare Chronocort® to Hydrocortisone</brief_title>
  <official_title>An Open Label, Randomised, Single Dose, 3-period Crossover Study in Healthy Volunteers to: a) Compare the Pharmacokinetics of Chronocort® Formulations Versus Immediate Release Hydrocortisone, and (b) Determine the Dose Proportionality of Chronocort® Formulations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Diurnal Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Simbec Research</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Diurnal Limited</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was an open label, randomized, single dose, three period crossover pharmacokinetic study&#xD;
      of Chronocort® in 30 healthy male volunteers. The study was conducted in smaller sub groups&#xD;
      (Group 1, n=18 and Group 2, n=12).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2010</start_date>
  <completion_date type="Actual">April 2010</completion_date>
  <primary_completion_date type="Actual">April 2010</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Derived pharmacokinetic parameter: Tmax</measure>
    <time_frame>24 hours</time_frame>
    <description>Tmax measures the time at which Cmax - maximum serum concentration - is observed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Derived pharmacokinetic parameter: Tlag</measure>
    <time_frame>24 hours</time_frame>
    <description>Tlag measures the delay between dosing and being able to observe the drug/metabolite within the sampling area (e.g., blood serum)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Derived pharmacokinetic parameter: Cmax</measure>
    <time_frame>24 hours</time_frame>
    <description>Cmax measures the time taken for the drug/metabolite to reach maximum serum concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Derived pharmacokinetic parameter: AUC(0 - t) (Area under the curve)</measure>
    <time_frame>24 hours</time_frame>
    <description>Area under the serum concentration versus time curve from time</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Derived pharmacokinetic parameter: AUC(0-∞)(Area under the curve)</measure>
    <time_frame>24 hours</time_frame>
    <description>Area under the serum concentration versus time curve from time = 0h extrapolated to infinity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Derived pharmacokinetic parameter: CL</measure>
    <time_frame>24 hours</time_frame>
    <description>Time to drug clearance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Derived pharmacokinetic parameter: T1/2</measure>
    <time_frame>24 hours</time_frame>
    <description>Time required to reach 1/2 Cmax</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Congenital Adrenal Hyperplasia</condition>
  <condition>Adrenal Insufficiency</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers in group 1 received the following interventions:&#xD;
Chronocort® 30 mg given at night (~ 23:00h) as a combination of one 10mg capsule and one 20mg capsule (n=18).&#xD;
Chronocort® 30mg given as one 20mg capsule at night (~ 23:00h) and as one 10mg capsule in the morning (~ 7:00h) following the initial night-time dose (n=18).&#xD;
Hydrocortisone 30mg given at night (~ 23:00h) given as three 10mg tablets (n=18).&#xD;
Each administration of IMP was separated by a washout period of at least 7 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers in group 2 received the following interventions:&#xD;
Chronocort® 5mg given at night (~ 23:00h) as one 5mg capsule (n=12).&#xD;
Chronocort® 10mg given at night (~ 23:00h) as one 10mg capsule (n=12).&#xD;
Chronocort® 20mg given at night (~ 23:00h) as one 20mg capsule (n=12).&#xD;
Each administration of IMP was separated by a washout period of at least 7 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrocortisone</intervention_name>
    <description>Generic hydrocortisone</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chronocort</intervention_name>
    <description>Modified formulation of hydrocortisone</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male volunteers between 18 and 60 years of age, inclusive (at screening).&#xD;
&#xD;
          -  Subjects with a Body Mass Index (BMI) of 21-28. Body Mass Index = Body weight (kg) /&#xD;
             (Height (m))2.&#xD;
&#xD;
          -  Subjects with no clinically significant abnormal serum biochemistry, haematology and&#xD;
             urine examination values within 14 days of the start of the study. The parameters&#xD;
             measured included those shown in Appendix 3 of the Study Protocol.&#xD;
&#xD;
          -  Subjects with a negative urinary drugs of abuse screen (including alcohol), determined&#xD;
             within 14 days of the start of the study.&#xD;
&#xD;
          -  Subjects with negative HIV and Hepatitis B and C results.&#xD;
&#xD;
          -  Subjects with no clinically significant abnormalities in 12-lead electrocardiogram&#xD;
             (ECG) determined within 14 days of the start of the study.&#xD;
&#xD;
          -  Subjects with no clinically-significant deviation outside the normal ranges for blood&#xD;
             pressure and pulse measurements.&#xD;
&#xD;
          -  Subjects and sexual partners must have used effective contraception methods during the&#xD;
             trial and for 3 months after the last dose, for example:&#xD;
&#xD;
               -  Oral contraceptive + condom&#xD;
&#xD;
               -  Intra-uterine device (IUD) + condom&#xD;
&#xD;
               -  Diaphragm with spermacide + condom&#xD;
&#xD;
          -  Subjects must have been available to complete the study.&#xD;
&#xD;
          -  Subjects must have satisfied a medical examiner about their fitness to participate in&#xD;
             the study.&#xD;
&#xD;
          -  Subjects must have provided written informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A clinically significant history of gastrointestinal disorder likely to influence drug&#xD;
             absorption.&#xD;
&#xD;
          -  Receipt of regular medication within 14 days of the first study day (including high&#xD;
             dose vitamins, dietary supplements or herbal remedies).&#xD;
&#xD;
          -  Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or&#xD;
             metabolic dysfunction.&#xD;
&#xD;
          -  A clinically significant history of previous allergy / sensitivity to Hydrocortisone.&#xD;
&#xD;
          -  A clinically significant history of drug or alcohol abuse.&#xD;
&#xD;
          -  Inability to communicate well with the Investigator (i.e., language problem, poor&#xD;
             mental development or impaired cerebral function).&#xD;
&#xD;
          -  Participation in a New Chemical Entity clinical study within the previous 16 weeks or&#xD;
             a marketed drug clinical study within the previous 12 weeks.&#xD;
&#xD;
          -  Subjects who had consumed more than 2 units of alcohol per day within seven (7) days&#xD;
             prior to the first dose or had consumed any alcohol within the 48 hour period prior to&#xD;
             the first dose.&#xD;
&#xD;
          -  Donation of 450ml or more blood within the previous 12 weeks.&#xD;
&#xD;
          -  Subjects who worked shifts (i.e. regularly alternated between days, afternoons and&#xD;
             nights).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Salvatore Febbraro</last_name>
    <role>Principal Investigator</role>
    <affiliation>Simbec Research</affiliation>
  </overall_official>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>January 11, 2017</last_update_submitted>
  <last_update_submitted_qc>January 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 12, 2017</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>Adrenal Hyperplasia, Congenital</mesh_term>
    <mesh_term>Adrenogenital Syndrome</mesh_term>
    <mesh_term>Adrenal Insufficiency</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrocortisone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03019614
org study id: DIUR-001
nct id: NCT03019614
lead sponsor: 
collaborator: 
has dmc: No
This was an open label, randomized, single dose, three period crossover pharmacokinetic study
      of Chronocort® in 30 healthy male volunteers. The study was conducted in smaller sub groups
      (Group 1, n=18 and Group 2, n=12).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Derived pharmacokinetic parameter: Tmax
time frame: 24 hours
description: Tmax measures the time at which Cmax - maximum serum concentration - is observed
measure: Derived pharmacokinetic parameter: Tlag
time frame: 24 hours
description: Tlag measures the delay between dosing and being able to observe the drug/metabolite within the sampling area (e.g., blood serum)
measure: Derived pharmacokinetic parameter: Cmax
time frame: 24 hours
description: Cmax measures the time taken for the drug/metabolite to reach maximum serum concentration
measure: Derived pharmacokinetic parameter: AUC(0 - t) (Area under the curve)
time frame: 24 hours
description: Area under the serum concentration versus time curve from time
measure: Derived pharmacokinetic parameter: AUC(0-∞)(Area under the curve)
time frame: 24 hours
description: Area under the serum concentration versus time curve from time = 0h extrapolated to infinity
measure: Derived pharmacokinetic parameter: CL
time frame: 24 hours
description: Time to drug clearance
measure: Derived pharmacokinetic parameter: T1/2
time frame: 24 hours
description: Time required to reach 1/2 Cmax
arm group label: Group 1
arm group type: Experimental
description: Volunteers in group 1 received the following interventions:
Chronocort® 30 mg given at night (~ 23:00h) as a combination of one 10mg capsule and one 20mg capsule (n=18).
Chronocort® 30mg given as one 20mg capsule at night (~ 23:00h) and as one 10mg capsule in the morning (~ 7:00h) following the initial night-time dose (n=18).
Hydrocortisone 30mg given at night (~ 23:00h) given as three 10mg tablets (n=18).
Each administration of IMP was separated by a washout period of at least 7 days.
arm group label: Group 2
arm group type: Experimental
description: Volunteers in group 2 received the following interventions:
Chronocort® 5mg given at night (~ 23:00h) as one 5mg capsule (n=12).
Chronocort® 10mg given at night (~ 23:00h) as one 10mg capsule (n=12).
Chronocort® 20mg given at night (~ 23:00h) as one 20mg capsule (n=12).
Each administration of IMP was separated by a washout period of at least 7 days.
intervention type: Drug
intervention name: Hydrocortisone
description: Generic hydrocortisone
arm group label: Group 1
intervention type: Drug
intervention name: Chronocort
description: Modified formulation of hydrocortisone
arm group label: Group 1
arm group label: Group 2
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Salvatore Febbraro
role: Principal Investigator
affiliation: Simbec Research
responsible party type: Sponsor
mesh term: Adrenal Hyperplasia, Congenital
mesh term: Adrenogenital Syndrome
mesh term: Adrenal Insufficiency
mesh term: Hyperplasia
mesh term: Hydrocortisone
sharing ipd: No