<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/NCT02240290</url>
  </required_header>
  <id_info>
    <org_study_id>PD0026</org_study_id>
    <secondary_id>2013-002640-85</secondary_id>
    <secondary_id>NL46031.056.13</secondary_id>
    <nct_id>NCT02240290</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Absorption, Distribution, Break Down and Elimination and the Safety of 14C-Labeled Tozadenant</brief_title>
  <official_title>A Single-Center, Open-Label Study of Excretion Balance, Pharmacokinetics, and Metabolism of 14C-Labeled Tozadenant After 240 mg Single Oral Dose Administration in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biotie Therapies Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PRA Health Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tandem Labs</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xceleron Inc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Biotie Therapies Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to investigate how tozadenant is absorbed, distributed, broken&#xD;
      down and eliminated from the body. The compound to be administered will be radiolabeled. This&#xD;
      enables the investigator to trace the compound in blood, urine, feces, expired air and track&#xD;
      what happens to it.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PD0026 is a Phase 1, single-center, open-label, single-dose study to investigate the&#xD;
      absorption, distribution, metabolism, and excretion (ADME) of 14C-labeled tozadenant. The&#xD;
      primary objective is to determine the mass balance and the pharmacokinetics (PK) of total&#xD;
      radioactivity in 6 healthy male subjects following a single oral dose of 14C-labeled&#xD;
      tozadenant. Secondary objectives are to determine the PK of Tozadenant, to identify and&#xD;
      quantify metabolites of tozadenant, and to gain further information on the tolerability and&#xD;
      safety of tozadenant.&#xD;
&#xD;
      The variables related to the radiocarbon activity include the total radioactivity&#xD;
      concentration in whole blood and plasma; the total radioactivity excretion in urine, feces,&#xD;
      and expired air; and the corresponding PK parameters.&#xD;
&#xD;
      The concentrations and the corresponding PK parameters of tozadenant over time will be&#xD;
      determined in plasma, urine, and feces.&#xD;
&#xD;
      In addition, the metabolites of tozadenant will be identified and quantified. The safety and&#xD;
      tolerability variables include adverse events (AEs), vital signs, physical examination,&#xD;
      standard 12 lead electrocardiogram (ECG) intervals, and clinical laboratory results.&#xD;
&#xD;
      The study will consist of a Screening Period of up to 20 days (Days -21 to -2) and a Study&#xD;
      Period of 15 days. Therefore, the maximum duration of participation from Screening until&#xD;
      discharge from the clinic for a subject is 35 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 1</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of total radioactivity concentration in whole blood, plasma, urine, feces and expired air, and cumulative percentage of radioactive dose in urine and feces, and total mass balance during the study (approximately 14 days)</measure>
    <time_frame>Samples collected during Screening Visit - Day 14 (maximum of 14 days)</time_frame>
    <description>Time evolution of radioactivity in plasma, blood, urine, feces and expired air from pre-dose to day 14. Cumulative time evolution of percentage of radioactivity in urine, feces, expired air and total. Total mass balance in percentage of dose.&#xD;
This outcome measure is a composite outcome. This means that multiple measurements will be reflected as one value for each study arm.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite pharmacokinetic parameters of the total radioactivity during the study (approximately 14 days)</measure>
    <time_frame>Samples collected during Screening Visit - Day 14 (maximum of 14 days)</time_frame>
    <description>Pharmacokinetics parameters computed on radioactivity concentrations:&#xD;
Plasma and blood: Cmax, tmax, AUC(0-t), apparent t1/2, AUC, elimination constant (λz)&#xD;
Cumulative amount excreted in urine, feces, and expired air&#xD;
This outcome measure is a composite outcome. This means that multiple measurements will be reflected as one value for each study arm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite pharmacokinetic parameters of tozadenant during the study (approximately 14 days)</measure>
    <time_frame>Samples collected during Screening Visit - Day 14 (maximum of 14 days)</time_frame>
    <description>The pharmacokinetics of tozadenant in plasma and urine are evaluated using the classical set of PK parameters: Cmax, tmax, AUC(0-t), AUC, λz, t1/2, Vz/F, CL/F, Ae, fe, CLR.&#xD;
This outcome measure is a composite outcome. This means that multiple measurements will be reflected as one value for each study arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification and quantification of metabolites of tozadenant in plasma and excreta during the study (approximately 14 days)</measure>
    <time_frame>Samples collected during Screening Visit - Day 14 (maximum of 14 days)</time_frame>
    <description>For structural identification, metabolites of tozadenant in the collected HPLC fractions, using quadrupole time-of-flight mass spectrometry will be identified from plasma and excreta samples. Quantification of metabolites.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>N/A, as Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>tozadenant</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of 240 mg tozadenant (four 60 mg tablets) and a 74 kBq (2 μCi) 14C-labeled tozadenant capsule will be administered with 240 mL of water.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tozadenant tablet</intervention_name>
    <description>Active substance: tozadenant Pharmaceutical form: Tablet Concentration: 240 mg Route of Administration: Oral administration</description>
    <arm_group_label>tozadenant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>C14-tozadenant capsule</intervention_name>
    <description>Active substance: C14-tozadenant Pharmaceutical form: Capsule Concentration: 74 kBq (2 μCi) Route of administration: Oral administration</description>
    <arm_group_label>tozadenant</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is a male between the ages of 18 and 55 years inclusive; subject may be of any&#xD;
             racial group&#xD;
&#xD;
          -  Subject is informed and given ample time and opportunity to think about his&#xD;
             participation and has signed and dated the Independent Ethics Committee (IEC) approved&#xD;
             written Informed Consent form&#xD;
&#xD;
          -  Subject is considered reliable and capable of adhering to the protocol, according to&#xD;
             the judgment of the Investigator, and is capable of communicating satisfactorily with&#xD;
             the Investigator and complying with all study requirements&#xD;
&#xD;
          -  Subject has a body mass index (BMI) between 18 to 30 kg/m², inclusive, and weighs at&#xD;
             least 50 kg&#xD;
&#xD;
          -  In the opinion of the Investigator, determined on the basis of the medical history and&#xD;
             a general clinical examination at Screening, the subject has no clinically relevant&#xD;
             cardiovascular, renal, gastrointestinal, hepatic, metabolic, endocrine, neurological&#xD;
             or psychiatric abnormalities, and the subject is in general good health&#xD;
&#xD;
          -  Subject is a nonsmoker, or has stopped smoking for at least 3 months prior to the&#xD;
             Screening Visit&#xD;
&#xD;
          -  Subject has clinical laboratory test results within the reference ranges of the&#xD;
             laboratory. Subjects with isolated laboratory test results that are outside the&#xD;
             reference ranges will be allowed to enroll at the discretion of the Investigator, so&#xD;
             long as these results are deemed by the Investigator to be clinically nonsignificant&#xD;
&#xD;
          -  Subject has Blood Pressure (BP) and pulse rate within normal range in supine position&#xD;
             after 5 minutes rest (SBP: 90 to 140 mmHg, DBP: 50 to 90 mmHg, pulse rate: 45 to 100&#xD;
             bpm). Subjects with vital sign results that are outside the specified ranges and that&#xD;
             are deemed clinically nonsignificant will be allowed to enroll at the discretion of&#xD;
             the Investigator&#xD;
&#xD;
          -  Subject has regular intestinal transit, in the opinion of the Investigator, determined&#xD;
             on the basis of absence of any history or current symptoms of recurrent constipation,&#xD;
             diarrhea, or any other gastrointestinal diseases. The mean stool frequency should be&#xD;
             at least once every 2 days&#xD;
&#xD;
          -  Subject confirms that, during the study period and for a period of 3 months after the&#xD;
             final dose, when having sexual intercourse with a woman of childbearing potential, he&#xD;
             will use a barrier contraceptive (eg, condom) AND that the respective partner will use&#xD;
             an additional contraceptive method. Subject should also agree not to donate semen&#xD;
             during this period of time&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has previously participated in this study or another tozadenant study&#xD;
&#xD;
          -  Subject is currently participating in or has participated in another study of an&#xD;
             investigational medicinal product or medical device in the last 3 months or 5&#xD;
             half-lives (whichever is longer)&#xD;
&#xD;
          -  Subject has a history of exposure to ionizing radiations (except radiography) or has&#xD;
             participated in another Absorption, Distribution, Metabolism, and Excretion (ADME)&#xD;
             study with a radiation burden &gt;0.1 mSv in the period of 1 year before Screening&#xD;
&#xD;
          -  Subject has a history of, or present, medical or psychiatric condition that, in the&#xD;
             opinion of the Investigator, could jeopardize or would compromise the subject's&#xD;
             ability to participate in this study&#xD;
&#xD;
          -  The subject has a known hypersensitivity to any components of the tozadenant&#xD;
             formulation or to similar drugs (A2a antagonists), or has a history of drug or other&#xD;
             relevant allergy that, in the opinion of the Investigator or UCB Study Physician,&#xD;
             contraindicates their participation&#xD;
&#xD;
          -  Subject has a known clinically relevant allergy or known severe adverse reaction to&#xD;
             any drug, or known or suspected clinically relevant drug hypersensitivity that, in the&#xD;
             opinion of the Investigator, could jeopardize or would compromise the subject's&#xD;
             ability to participate in this study&#xD;
&#xD;
          -  Subject has a history or presence of drug or alcohol dependency or tests positive for&#xD;
             drugs or alcohol (urine tests) at Screening or Day -1&#xD;
&#xD;
          -  Subject consumes more than 28 units of alcohol per week (330 mL of 5% alcohol by&#xD;
             volume beer=2 units; 125 mL of 12% wine=1.5 units; 50 mL of 40% spirits=2 units).&#xD;
&#xD;
          -  Subject consumes more than 600 mg of caffeine/ day (1 cup of coffee contains&#xD;
             approximately 100 mg of caffeine, 1 cup of tea contains approximately 30 mg of&#xD;
             caffeine, and 1 glass of cola contains approximately 20 mg of caffeine)&#xD;
&#xD;
          -  Subject has a diet that deviates notably from the &quot;normal&quot; amounts of protein,&#xD;
             carbohydrate, and fat, as judged by the Investigator (eg, vegans)&#xD;
&#xD;
          -  Subject has received any prescription or nonprescription medicines, including enzyme&#xD;
             inhibitors or inducers, over-the-counter remedies, vitamins outside the recommended&#xD;
             daily dose limits, herbal, and dietary supplements (including St. John's Wort) within&#xD;
             14 days or 5 half-lives (whichever is longer) prior to administration of study&#xD;
             medication. Occasional paracetamol use is allowed within the 14 days before the study&#xD;
             drug administration, with a maximal dose of 2 g/day and a maximal cumulative dose of&#xD;
             10 g per 14 days, and during the study for the treatment of mild symptoms (eg,&#xD;
             headache or pain relief)&#xD;
&#xD;
          -  Subject has consumed any grapefruit, grapefruit juice, grapefruit containing products,&#xD;
             or star fruit within 14 days prior to the planned administration of the study drug&#xD;
&#xD;
          -  Subject tests positive for human immunodeficiency virus (HIV) -1/2 antibody (HIV-1/2&#xD;
             Ab), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV-Ab).&#xD;
&#xD;
          -  Subject has a history or present condition of hepatic disorders, including but not&#xD;
             limited to elevation of liver enzymes (alanine aminotransferase [ALT], aspartate&#xD;
             aminotransferase [AST], alkaline phosphatase, and gamma-glutamyltransferase [GGT]) at&#xD;
             the upper limit of laboratory reference ranges&#xD;
&#xD;
          -  Subject has a history of thyroid abnormalities&#xD;
&#xD;
          -  Subject has had significant blood loss or has donated or received 50 mL or more of&#xD;
             blood within 60 days prior to drug administration, or has donated plasma or platelets&#xD;
             within 14 days prior to first drug administration for this study&#xD;
&#xD;
          -  Subject shows any sign of orthostatic hypotension at Screening, defined as:&#xD;
&#xD;
               -  A ≥20 mmHg decrease in SBP, and/or ≥10 mmHg decrease in DBP if the resultant SBP&#xD;
                  falls below 90mmHg and/or DBP falls below 60 mmHg. Blood pressure and pulse rate&#xD;
                  will be recorded after 5 minutes of rest in the supine position and after 2&#xD;
                  minutes of rest in the standing position&#xD;
&#xD;
               -  A ≥40 mmHg decrease in SBP, and/or ≥20 mmHg decrease in DBP, regardless of&#xD;
                  resultant SBP and/or DBP. Blood pressure and pulse rate will be recorded after 5&#xD;
                  minutes of rest in the supine position and after 2 minutes of rest in the&#xD;
                  standing position&#xD;
&#xD;
          -  Subject has an abnormality in the 12-lead ECG at Screening that results, in the&#xD;
             opinion of the Investigator, in an increase in the risks associated with participating&#xD;
             in the study. In addition, any subject with any of the following findings will be&#xD;
             excluded:&#xD;
&#xD;
               -  QT interval corrected for heart rate using Fridericia's formula (QTcF) &gt;450 ms in&#xD;
                  ECG&#xD;
&#xD;
               -  Bundle branch blocks and other conduction abnormalities other than mild first&#xD;
                  degree atrioventricular block (defined as PR interval ≥220 ms)&#xD;
&#xD;
               -  Irregular rhythms other than sinus arrhythmia or occasional, rare&#xD;
                  supraventricular or ventricular ectopic beats&#xD;
&#xD;
               -  In the judgment of the Investigator, T-wave configurations are not of sufficient&#xD;
                  quality for assessing QT interval duration&#xD;
&#xD;
          -  Subject has a history of unexplained syncope, or a family history of unexplained&#xD;
             sudden death or sudden death due to long QT syndrome&#xD;
&#xD;
          -  Subject has a history or present condition of respiratory or cardiovascular disorders&#xD;
             (eg, cardiac insufficiency, coronary heart disease, hypertension, arrhythmia,&#xD;
             tachyarrhythmia, or myocardial infarction)&#xD;
&#xD;
          -  Subject has a history or present condition of malignancy, gastrointestinal bleeding,&#xD;
             or anal fissures&#xD;
&#xD;
          -  Subject is unable to understand the constraints of full urine and stool collection&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pharmaceutical Research Associates Group B.V.</name>
      <address>
        <city>Zuidlaren</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>August 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>August 3, 2017</last_update_submitted>
  <last_update_submitted_qc>August 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>C14</keyword>
  <keyword>Dosimetry</keyword>
  <keyword>Mass balance</keyword>
  <keyword>ADME</keyword>
  <!-- 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/NCT02240290
org study id: PD0026
secondary id: 2013-002640-85
secondary id: NL46031.056.13
nct id: NCT02240290
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of the study is to investigate how tozadenant is absorbed, distributed, broken
      down and eliminated from the body. The compound to be administered will be radiolabeled. This
      enables the investigator to trace the compound in blood, urine, feces, expired air and track
      what happens to it.
PD0026 is a Phase 1, single-center, open-label, single-dose study to investigate the
      absorption, distribution, metabolism, and excretion (ADME) of 14C-labeled tozadenant. The
      primary objective is to determine the mass balance and the pharmacokinetics (PK) of total
      radioactivity in 6 healthy male subjects following a single oral dose of 14C-labeled
      tozadenant. Secondary objectives are to determine the PK of Tozadenant, to identify and
      quantify metabolites of tozadenant, and to gain further information on the tolerability and
      safety of tozadenant.

      The variables related to the radiocarbon activity include the total radioactivity
      concentration in whole blood and plasma; the total radioactivity excretion in urine, feces,
      and expired air; and the corresponding PK parameters.

      The concentrations and the corresponding PK parameters of tozadenant over time will be
      determined in plasma, urine, and feces.

      In addition, the metabolites of tozadenant will be identified and quantified. The safety and
      tolerability variables include adverse events (AEs), vital signs, physical examination,
      standard 12 lead electrocardiogram (ECG) intervals, and clinical laboratory results.

      The study will consist of a Screening Period of up to 20 days (Days -21 to -2) and a Study
      Period of 15 days. Therefore, the maximum duration of participation from Screening until
      discharge from the clinic for a subject is 35 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Composite of total radioactivity concentration in whole blood, plasma, urine, feces and expired air, and cumulative percentage of radioactive dose in urine and feces, and total mass balance during the study (approximately 14 days)
time frame: Samples collected during Screening Visit - Day 14 (maximum of 14 days)
description: Time evolution of radioactivity in plasma, blood, urine, feces and expired air from pre-dose to day 14. Cumulative time evolution of percentage of radioactivity in urine, feces, expired air and total. Total mass balance in percentage of dose.
This outcome measure is a composite outcome. This means that multiple measurements will be reflected as one value for each study arm.
measure: Composite pharmacokinetic parameters of the total radioactivity during the study (approximately 14 days)
time frame: Samples collected during Screening Visit - Day 14 (maximum of 14 days)
description: Pharmacokinetics parameters computed on radioactivity concentrations:
Plasma and blood: Cmax, tmax, AUC(0-t), apparent t1/2, AUC, elimination constant (λz)
Cumulative amount excreted in urine, feces, and expired air
This outcome measure is a composite outcome. This means that multiple measurements will be reflected as one value for each study arm.
measure: Composite pharmacokinetic parameters of tozadenant during the study (approximately 14 days)
time frame: Samples collected during Screening Visit - Day 14 (maximum of 14 days)
description: The pharmacokinetics of tozadenant in plasma and urine are evaluated using the classical set of PK parameters: Cmax, tmax, AUC(0-t), AUC, λz, t1/2, Vz/F, CL/F, Ae, fe, CLR.
This outcome measure is a composite outcome. This means that multiple measurements will be reflected as one value for each study arm.
measure: Identification and quantification of metabolites of tozadenant in plasma and excreta during the study (approximately 14 days)
time frame: Samples collected during Screening Visit - Day 14 (maximum of 14 days)
description: For structural identification, metabolites of tozadenant in the collected HPLC fractions, using quadrupole time-of-flight mass spectrometry will be identified from plasma and excreta samples. Quantification of metabolites.
arm group label: tozadenant
arm group type: Experimental
description: A single dose of 240 mg tozadenant (four 60 mg tablets) and a 74 kBq (2 μCi) 14C-labeled tozadenant capsule will be administered with 240 mL of water.
intervention type: Drug
intervention name: tozadenant tablet
description: Active substance: tozadenant Pharmaceutical form: Tablet Concentration: 240 mg Route of Administration: Oral administration
arm group label: tozadenant
intervention type: Drug
intervention name: C14-tozadenant capsule
description: Active substance: C14-tozadenant Pharmaceutical form: Capsule Concentration: 74 kBq (2 μCi) Route of administration: Oral administration
arm group label: tozadenant
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Netherlands
responsible party type: Sponsor