<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/NCT01730482</url>
  </required_header>
  <id_info>
    <org_study_id>116435</org_study_id>
    <nct_id>NCT01730482</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Absorption, Metabolism and Excretion of Migalastat Hydrochloride (AT1001-014)</brief_title>
  <official_title>A Phase 1 Study to Investigate the Absorption, Metabolism and Excretion of [14C] AT1001 (Migalastat Hydrochloride) Following a Single Oral Administration in Healthy Volunteers (AT1001-014)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amicus Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amicus Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to describe the metabolism of AT1001 (migalastat HCl) and the&#xD;
      contribution of metabolism and urinary excretion to its overall elimination as part of the&#xD;
      continuing assessment of the safety and effectiveness of the drug.&#xD;
&#xD;
      This is a Phase 1, single-site, open-label, single dose study of the absorption, metabolism&#xD;
      and excretion of radiolabeled AT1001 in healthy male subjects between 30 and 55 years of age,&#xD;
      inclusive. Six subjects will be dosed, with the goal of having at least 4 subjects complete&#xD;
      the study through follow-up. All subjects will be screened within 28 days before admission to&#xD;
      the Clinical Unit. Subjects will be confined to the clinical unit for 10 days after dosing&#xD;
      and will return to the clinic for a follow-up visit 28 days after dosing.&#xD;
&#xD;
      Each subject will receive a single oral dose of AT1001 as an aqueous solution containing 150&#xD;
      mg [14C] AT1001 (1 μCi). Blood, duodenal bile, expired air, urine, and feces samples will be&#xD;
      collected at specified time points after dosing throughout the period of confinement at the&#xD;
      study site. Safety will be assessed throughout the study by monitoring clinical laboratory&#xD;
      tests, ECGs, physical examinations, vital signs, and adverse events. The total duration of&#xD;
      the study for each subject is approximately 8 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">September 2011</completion_date>
  <primary_completion_date type="Actual">September 2011</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recovery of total radioactivity in urine</measure>
    <time_frame>Days 1 to 11</time_frame>
    <description>Urine will be collected: pre-dose (-12-0 hours), 0-12 and 12-24 hours on Day 1, 24-hourly on Days 2-10; the last sample will be collected on Day 11. Total radioactivity excreted in urine will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in urine, divided by the duration of collection. The percentage of dose excreted in urine will be calculated from the total amount excreted in urine divided by the dose administered, multiplied by 100.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recovery of total radioactivity in feces</measure>
    <time_frame>Days 1 to 11</time_frame>
    <description>Feces will be collected: predose (-24 to 0 hours); all bowel movements post-dose will be collected on Days 1 to 10; the last sample will be collected on Day 11. Total radioactivity excreted in feces will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in feces, divided by the duration of collection. The percentage of dose excreted in feces will be calculated from the total amount excreted in feces divided by the dose administered, multiplied by 100.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Presence of radioactivity in expired air</measure>
    <time_frame>Day 1</time_frame>
    <description>Expired air will be collected: pre-dose and at 2, 4, 6 and 24 hours after dosing. Each subject will blow into a measured volume of sodium hydroxide solution containing phenolphthalein, until an indicator changes color, showing that the sodium hydroxide is saturated. This sodium hydroxide solution will be analysed for radioactive content. If radioactivity is detected the total amount in expired air during the collection period will be calculated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma AT1001 pharmacokinetic parameters</measure>
    <time_frame>Days 1 to 10</time_frame>
    <description>Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma AT1001: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma total radioactivity pharmacokinetic parameters</measure>
    <time_frame>Days 1 to 10</time_frame>
    <description>Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma radioactivity: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events as a measure of safety and tolerability</measure>
    <time_frame>Day 1 to Day 29</time_frame>
    <description>Adverse events (AEs) will be collected from the start of Investigation Product and until the follow-up visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure of clinical laboratory test values to access safety and tolerability</measure>
    <time_frame>Upto 8 weeks</time_frame>
    <description>Clinical laboratory tests will include hematology, coagulation tests, clinical chemistry, urinalysis, drug and toxicology screen, Hepatitis A and HIV screen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physical examination to access safety and tolerability</measure>
    <time_frame>Upto 8 weeks</time_frame>
    <description>Physical examination results will be categorized as normal, abnormal clinically significant, or abnormal not clinically significant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure of vital signs to access safety and tolerability</measure>
    <time_frame>Upto 8 weeks</time_frame>
    <description>Vital sign measurements will include pulse, respiratory rate, blood pressure, and oral temperature). Subjects should be in a supine position for at least 5 minutes prior to taking measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure of ECG to access safety and tolerability</measure>
    <time_frame>Upto 8 weeks</time_frame>
    <description>Electrocardiograph (ECG) is a machine that measures the electrical activity of the heart and records changes in the hearts' rhythm. All subjects will undergo ECG testing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The blood to plasma ratio of total radioactivity</measure>
    <time_frame>Day 1</time_frame>
    <description>The ratio of plasma to blood radioactivity will be calculated at 2, 4, 6 and 24 hours after administration of AT1001.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterization of metabolites in plasma, urine, duodenal bile and fecal homogenates</measure>
    <time_frame>Day -1 to Day 11</time_frame>
    <description>An Entero-Test capsule will be ingested to collect duodenal bile and will be removed after sample collection. Metabolite elucidation and identification will be performed in the collected plasma, urine doudenal bile, and fecal samples, if feasible, under a separate study. Results will be summarized in a separate report.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Fabry Disease</condition>
  <arm_group>
    <arm_group_label>[14C] AT1001 Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive a single oral dose of 150 mg of [14C] AT1001 as an aqueous solution containing 1 μCi AT1001 on Study Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C] AT1001</intervention_name>
    <description>150 mg of [14C] labelled AT1001 will be administered as a solution (prepared by weighing 150 mg of AT1001 powder and dissolving in 100 mL of water). The entire solution will be swallowed orally. After ingestion of study medication, the dosing bottle will be rinsed with 50 mL of water and this will be ingested by the subject. This rinse procedure should be performed twice. Following the second rinse ingestion, the subjects should be instructed to drink additional water to bring the total volume ingested to 240 mL.</description>
    <arm_group_label>[14C] AT1001 Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects between the ages of 30 and 55 years, inclusive&#xD;
&#xD;
          -  Body mass index (BMI) of &gt;=18.0 to &lt;=30.0 and weighing at least 60 kg&#xD;
&#xD;
          -  Anticipated, regular, average bowel movements of 1-2 per day&#xD;
&#xD;
          -  No clinically significant abnormal findings on the physical exam, vital signs, serum&#xD;
             chemistry, hematology, and urinalysis values, as deemed by the principal investigator&#xD;
&#xD;
          -  Willing to avoid taking of all over-the-counter medications 7 days and all&#xD;
             prescription drugs 14 days prior to Day -1&#xD;
&#xD;
          -  Willing to abstain from sexual intercourse or employ a barrier method of contraception&#xD;
             during the inpatient clinic confinement and until the follow-up visit&#xD;
&#xD;
          -  Willing to avoid ingestion of broccoli, brussels sprouts, grapefruit, grapefruit&#xD;
             juice, or charbroiled meat during the period of confinement in the clinical unit&#xD;
&#xD;
          -  Willingness to consume a fiber-rich diet during the period of confinement in the&#xD;
             clinic&#xD;
&#xD;
          -  Willingness to avoid vigorous physical activity during inpatient clinic confinement&#xD;
             and through the follow-up visit&#xD;
&#xD;
          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory&#xD;
             tests, other study procedures, and study restrictions&#xD;
&#xD;
          -  Provide written informed consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any previous or ongoing clinically significant illness, medical condition, medical&#xD;
             history, physical findings, ECG finding, or laboratory abnormality that, in the&#xD;
             investigator's opinion, could affect the safety of the subject, or alter the&#xD;
             absorption, distribution, metabolism, or excretion of the study drug, or could impair&#xD;
             the assessment of study results&#xD;
&#xD;
          -  History or presence of significant ophthalmic, cardiovascular, pulmonary, hepatic,&#xD;
             renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic&#xD;
             or psychiatric disease&#xD;
&#xD;
          -  History of a major surgical procedure within 30 days before screening&#xD;
&#xD;
          -  History of blood or plasma donation or blood loss (&gt;400 mL) within 60 days before&#xD;
             screening&#xD;
&#xD;
          -  History of drug or alcohol abuse or addiction within 2 years before screening&#xD;
&#xD;
          -  Intake of more than 2 alcoholic drinks per day within the past 7 days or use of&#xD;
             alcohol-, grapefruit-, or caffeine-containing foods or beverages within 72 hours prior&#xD;
             to Day -1&#xD;
&#xD;
          -  Self-reported smoker (occasional or frequent) or positive urine cotinine test&#xD;
             (measured at screening and baseline) exceeding the local laboratory's lower limit of&#xD;
             detection.&#xD;
&#xD;
          -  Presence or history of severe adverse reaction to any drug; history of&#xD;
             hypersensitivity or allergic reaction to AT1001 or related iminosugars&#xD;
&#xD;
          -  Receipt of any investigational agent or participation in any other interventional&#xD;
             clinical trial within the past 30 days&#xD;
&#xD;
          -  Participation in any clinical study involving administration of [14C] labeled&#xD;
             compound(s) within the last 12 months. A subject's previous effective dose will be&#xD;
             reviewed by the medical investigator to ensure there is no risk of&#xD;
             contamination/carryover into the current study&#xD;
&#xD;
          -  At Day -1, a drug toxicology screen positive for any illicit substances, or alcohol&#xD;
&#xD;
          -  Anticipated need for alcohol, tobacco, or any drug during the period of confinement in&#xD;
             the clinical unit&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor, Clinical Research</last_name>
    <role>Study Director</role>
    <affiliation>Amicus Therapeutics</affiliation>
  </overall_official>
  <verification_date>December 2013</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>December 17, 2013</last_update_submitted>
  <last_update_submitted_qc>December 17, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 18, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>excretion</keyword>
  <keyword>healthy volunteer</keyword>
  <keyword>migalastat hydrochloride</keyword>
  <keyword>AT1001</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>Fabry disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</mesh_term>
  </condition_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/NCT01730482
org study id: 116435
nct id: NCT01730482
lead sponsor: 
has dmc: No
This study is designed to describe the metabolism of AT1001 (migalastat HCl) and the
      contribution of metabolism and urinary excretion to its overall elimination as part of the
      continuing assessment of the safety and effectiveness of the drug.

      This is a Phase 1, single-site, open-label, single dose study of the absorption, metabolism
      and excretion of radiolabeled AT1001 in healthy male subjects between 30 and 55 years of age,
      inclusive. Six subjects will be dosed, with the goal of having at least 4 subjects complete
      the study through follow-up. All subjects will be screened within 28 days before admission to
      the Clinical Unit. Subjects will be confined to the clinical unit for 10 days after dosing
      and will return to the clinic for a follow-up visit 28 days after dosing.

      Each subject will receive a single oral dose of AT1001 as an aqueous solution containing 150
      mg [14C] AT1001 (1 μCi). Blood, duodenal bile, expired air, urine, and feces samples will be
      collected at specified time points after dosing throughout the period of confinement at the
      study site. Safety will be assessed throughout the study by monitoring clinical laboratory
      tests, ECGs, physical examinations, vital signs, and adverse events. The total duration of
      the study for each subject is approximately 8 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recovery of total radioactivity in urine
time frame: Days 1 to 11
description: Urine will be collected: pre-dose (-12-0 hours), 0-12 and 12-24 hours on Day 1, 24-hourly on Days 2-10; the last sample will be collected on Day 11. Total radioactivity excreted in urine will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in urine, divided by the duration of collection. The percentage of dose excreted in urine will be calculated from the total amount excreted in urine divided by the dose administered, multiplied by 100.
measure: Recovery of total radioactivity in feces
time frame: Days 1 to 11
description: Feces will be collected: predose (-24 to 0 hours); all bowel movements post-dose will be collected on Days 1 to 10; the last sample will be collected on Day 11. Total radioactivity excreted in feces will be calculated for the entire collection period. The excretion rate will be calculated from total radioactivity collected in feces, divided by the duration of collection. The percentage of dose excreted in feces will be calculated from the total amount excreted in feces divided by the dose administered, multiplied by 100.
measure: Presence of radioactivity in expired air
time frame: Day 1
description: Expired air will be collected: pre-dose and at 2, 4, 6 and 24 hours after dosing. Each subject will blow into a measured volume of sodium hydroxide solution containing phenolphthalein, until an indicator changes color, showing that the sodium hydroxide is saturated. This sodium hydroxide solution will be analysed for radioactive content. If radioactivity is detected the total amount in expired air during the collection period will be calculated.
measure: Plasma AT1001 pharmacokinetic parameters
time frame: Days 1 to 10
description: Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma AT1001: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.
measure: Plasma total radioactivity pharmacokinetic parameters
time frame: Days 1 to 10
description: Blood samples will be collected: Pre-dose, at 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 hours after dosing. Non-compartmental pharmacokinetic parameters will be calculated for plasma radioactivity: area under the drug concentration-time curve (AUC) from time zero to the time of the last measurable concentration, AUC from time zero to infinity, maximum observed drug concentration, time of the maximum drug concentration, apparent terminal elimination rate constant and apparent elimination half life.
measure: Number of subjects with adverse events as a measure of safety and tolerability
time frame: Day 1 to Day 29
description: Adverse events (AEs) will be collected from the start of Investigation Product and until the follow-up visit.
measure: Measure of clinical laboratory test values to access safety and tolerability
time frame: Upto 8 weeks
description: Clinical laboratory tests will include hematology, coagulation tests, clinical chemistry, urinalysis, drug and toxicology screen, Hepatitis A and HIV screen.
measure: Physical examination to access safety and tolerability
time frame: Upto 8 weeks
description: Physical examination results will be categorized as normal, abnormal clinically significant, or abnormal not clinically significant
measure: Measure of vital signs to access safety and tolerability
time frame: Upto 8 weeks
description: Vital sign measurements will include pulse, respiratory rate, blood pressure, and oral temperature). Subjects should be in a supine position for at least 5 minutes prior to taking measurements.
measure: Measure of ECG to access safety and tolerability
time frame: Upto 8 weeks
description: Electrocardiograph (ECG) is a machine that measures the electrical activity of the heart and records changes in the hearts' rhythm. All subjects will undergo ECG testing.
measure: The blood to plasma ratio of total radioactivity
time frame: Day 1
description: The ratio of plasma to blood radioactivity will be calculated at 2, 4, 6 and 24 hours after administration of AT1001.
measure: Characterization of metabolites in plasma, urine, duodenal bile and fecal homogenates
time frame: Day -1 to Day 11
description: An Entero-Test capsule will be ingested to collect duodenal bile and will be removed after sample collection. Metabolite elucidation and identification will be performed in the collected plasma, urine doudenal bile, and fecal samples, if feasible, under a separate study. Results will be summarized in a separate report.
arm group label: [14C] AT1001 Arm
arm group type: Experimental
description: Each subject will receive a single oral dose of 150 mg of [14C] AT1001 as an aqueous solution containing 1 μCi AT1001 on Study Day 1.
intervention type: Drug
intervention name: [14C] AT1001
description: 150 mg of [14C] labelled AT1001 will be administered as a solution (prepared by weighing 150 mg of AT1001 powder and dissolving in 100 mL of water). The entire solution will be swallowed orally. After ingestion of study medication, the dosing bottle will be rinsed with 50 mL of water and this will be ingested by the subject. This rinse procedure should be performed twice. Following the second rinse ingestion, the subjects should be instructed to drink additional water to bring the total volume ingested to 240 mL.
arm group label: [14C] AT1001 Arm
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Monitor, Clinical Research
role: Study Director
affiliation: Amicus Therapeutics
responsible party type: Sponsor
mesh term: Fabry Disease