<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/NCT01730469</url>
  </required_header>
  <id_info>
    <org_study_id>116431</org_study_id>
    <nct_id>NCT01730469</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function</brief_title>
  <official_title>An Open-Label Study to Determine the Safety and Pharmacokinetics of AT1001 in Subjects With Impaired Renal Function and Healthy Subjects With Normal Renal Function (AT1001-015)</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 will assess the safety, tolerability, and pharmacokinetics (PK) study of a single&#xD;
      dose of 150 mg AT1001 (migalastat HCl, GR181413A) administered orally to healthy subjects&#xD;
      with normal renal function and to subjects with mild, moderate, and severe renal impairment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be an open-label, non-randomized, multiple-center, sequential group, safety,&#xD;
      tolerability, and PK study of a single dose of AT1001 (migalastat HCl, GR181413A)&#xD;
      administered orally as a 150 mg dose in fasted healthy control male and female subjects with&#xD;
      normal renal function compared to mild, moderate, and severe renally-impaired subjects&#xD;
      (classified by level of creatinine clearance [CLcr] as determined by the Cockcroft-Gault&#xD;
      formula).&#xD;
&#xD;
      Screening will occur from Day -28 to Day -2. Subjects will check-in to the clinic on Day -1&#xD;
      and receive a single oral dose of 150 mg AT1001 on Day 1. Subjects will be discharged from&#xD;
      the clinic on Day 2 (if stable as determined by the Investigator) and return for daily visits&#xD;
      on Day 3 through Day 6 for a safety assessment and PK sampling. Subjects will undergo a&#xD;
      follow-up visit on Day 7 (+1) and an end of study visit on Day 10 (+1).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">April 2012</completion_date>
  <primary_completion_date type="Actual">April 2012</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>Number of subjects with adverse events to assess safety and tolerability</measure>
    <time_frame>Day 1 to Day 10 (+1)</time_frame>
    <description>Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical laboratory test values to assess safety and tolerability</measure>
    <time_frame>Day -28 to Day 10 (+1)</time_frame>
    <description>Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital signs to assess safety and tolerability</measure>
    <time_frame>Day -28 to Day 10 (+1)</time_frame>
    <description>Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physician examination to assess safety and tolerability</measure>
    <time_frame>Day -28 to Day 10 (+1)</time_frame>
    <description>Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measure of ECG to assess safety and tolerability</measure>
    <time_frame>Day -28 to Day 10 (+1)</time_frame>
    <description>Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm. All subjects will undergo ECG testing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration (Cmax) of AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the resultant maximum plasma concentration (Cmax) will be measured in subjects with impaired renal function and normal renal function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to achieve maximum concentration (Tmax) of AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and time to maximum concentration (tmax) will be measured in subjects with impaired renal function and normal renal function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal elimination half life (t1/2 ) of AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and and apparent terminal elimination half-life (t1/2) will be measured in subjects with impaired renal function and normal renal function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-t will be measured in subjects with impaired renal function and normal renal function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-inf will be measured in subjects with impaired renal function and normal renal function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal elimination rate constant for AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the apparent terminal elimination rate constant will be measured in subjects with impaired renal function and normal renal function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral clearance of AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral clearance will be measured in subjects with impaired renal function and normal renal function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oral volume of distribution of AT1001</measure>
    <time_frame>Day 1 to Day 6</time_frame>
    <description>Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral volume of distribution will be measured in subjects with impaired renal function and normal renal function</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Fabry Disease</condition>
  <arm_group>
    <arm_group_label>AT1001 150 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive a single oral dose of AT1001 150 mg administered orally with 240 mL room temperature water after at least a 4-hour fast</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AT1001 150 mg</intervention_name>
    <description>AT1001 150mg is available as a capsule</description>
    <arm_group_label>AT1001 150 mg</arm_group_label>
    <other_name>migalastat HCl</other_name>
    <other_name>GR181413A</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria All subjects&#xD;
&#xD;
          -  males or females aged 18 to 70 years inclusive (subjects with normal renal function,&#xD;
             mild or moderate renal impairment), and 18 to 75 years inclusive (subjects with severe&#xD;
             renal impairment)&#xD;
&#xD;
          -  body mass index 18.0 to 40.0 kilogram (kg)/square meter (m^2) inclusive&#xD;
&#xD;
          -  females who are non-pregnant, non-lactating, or postmenopausal for &gt;=1 year,&#xD;
             surgically sterile for &gt;= 90 days, or agree to use approved methods of contraception&#xD;
&#xD;
          -  males will be sterile or use approved methods of contraception&#xD;
&#xD;
          -  understands and signs informed consent form Healthy subjects with normal renal&#xD;
             function&#xD;
&#xD;
          -  negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in&#xD;
&#xD;
          -  good health with no clinically significant medical history, physical examination,&#xD;
             vital signs, or 12-lead ECG&#xD;
&#xD;
          -  clinical laboratory tests within the reference range or not clinically significant&#xD;
&#xD;
          -  normal renal function (estimated CLcr &gt;90 mL/min) at Screening Subjects with mild,&#xD;
             moderate or severe renal impairment&#xD;
&#xD;
          -  negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in&#xD;
             or verification of a prescription for a positive test&#xD;
&#xD;
          -  renal impairment (estimated CLcr &lt;90 mL/min)&#xD;
&#xD;
          -  evidence of stable renal impairment defined as two separate estimated CLcr values&#xD;
             within 25%&#xD;
&#xD;
          -  clinical laboratory results consistent with their renal condition or of no clinical&#xD;
             significance for the study&#xD;
&#xD;
          -  abnormal laboratory values must not be clinically significant. Anemia secondary to&#xD;
             renal disease is acceptable if hemoglobin is ≥9 g/dL and no clinically significant&#xD;
             symptoms. Liver enzymes and bilirubin must be below twice the upper normal level&#xD;
&#xD;
          -  subjects with renal impairment must have stable underlying medical conditions &lt; 90&#xD;
             days before study start&#xD;
&#xD;
          -  stable medication regimen(s) (no new drug(s) or changed dosage(s) &lt;30 days before&#xD;
             study drug)&#xD;
&#xD;
          -  in good general health, allowing for concurrent illnesses associated with chronic&#xD;
             kidney disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All subjects:&#xD;
&#xD;
          -  history of hypersensitivity or allergies to any drug, unless approved by the&#xD;
             Investigator and reviewed by Sponsor/Medical Monitor&#xD;
&#xD;
          -  participation in a study with receipt of an investigational drug &lt; 5 half-lives or 30&#xD;
             days (whichever is longer) before Check-in&#xD;
&#xD;
          -  use of alcohol, grapefruit, or caffeine-containing foods or beverages &lt; 72 hours&#xD;
             before Check-in, unless approved by the Investigator and reviewed by the&#xD;
             Sponsor/Medical Monitor&#xD;
&#xD;
          -  poor peripheral venous access&#xD;
&#xD;
          -  whole blood donation &lt; 56 days before dosing or plasma donation &lt; 14 days before&#xD;
             dosing&#xD;
&#xD;
          -  receipt of blood products &lt; 2 months before Check-in&#xD;
&#xD;
          -  history or presence of any clinically significant abnormal ECG&#xD;
&#xD;
          -  history of alcoholism or drug addiction &lt; 1 year before Check-in&#xD;
&#xD;
          -  positive test for HIV antibody, HBsAg or anti-HCV&#xD;
&#xD;
          -  pregnant or breastfeeding&#xD;
&#xD;
        Healthy subjects with normal renal function:&#xD;
&#xD;
          -  use of any tobacco- or nicotine-containing products &lt; 6 months before Check-in&#xD;
&#xD;
          -  clinically significant (history of or active) cardiac, hepatic, pulmonary, endocrine,&#xD;
             neurological, infectious, gastrointestinal, hematologic, oncologic, or psychiatric&#xD;
             disease putting the subject at increased risk or could interfere with study objectives&#xD;
&#xD;
          -  screening laboratory values outside normal range and deemed clinically significant by&#xD;
             the Investigator&#xD;
&#xD;
          -  use of a prescription drug &lt; 14 days of dosing or a non-prescription drug &lt; 7 days&#xD;
             before dosing or need of concomitant medication during the study&#xD;
&#xD;
        Subjects with mild, moderate, or severe renal impairment:&#xD;
&#xD;
          -  unstable disease (concurrent medical conditions that have changed significantly &lt; 90&#xD;
             days)&#xD;
&#xD;
          -  changes in concomitant prescription medications &lt; 30 days before dosing or expected&#xD;
             changes during study&#xD;
&#xD;
          -  use of new non-prescription medication &lt; 30 days before dosing&#xD;
&#xD;
          -  renal transplant&#xD;
&#xD;
          -  acute or chronic non-renal condition limiting the subject's ability to complete and/or&#xD;
             participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 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>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Costa Mesa</city>
        <state>California</state>
        <zip>92626</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</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>August 2, 2017</last_update_submitted>
  <last_update_submitted_qc>August 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinetics</keyword>
  <keyword>GR181413</keyword>
  <keyword>Safety</keyword>
  <keyword>AT1001</keyword>
  <keyword>Migalastat hydrochloride</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</mesh_term>
    <mesh_term>Renal Insufficiency</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/NCT01730469
org study id: 116431
nct id: NCT01730469
lead sponsor: 
has dmc: No
This study will assess the safety, tolerability, and pharmacokinetics (PK) study of a single
      dose of 150 mg AT1001 (migalastat HCl, GR181413A) administered orally to healthy subjects
      with normal renal function and to subjects with mild, moderate, and severe renal impairment.
This will be an open-label, non-randomized, multiple-center, sequential group, safety,
      tolerability, and PK study of a single dose of AT1001 (migalastat HCl, GR181413A)
      administered orally as a 150 mg dose in fasted healthy control male and female subjects with
      normal renal function compared to mild, moderate, and severe renally-impaired subjects
      (classified by level of creatinine clearance [CLcr] as determined by the Cockcroft-Gault
      formula).

      Screening will occur from Day -28 to Day -2. Subjects will check-in to the clinic on Day -1
      and receive a single oral dose of 150 mg AT1001 on Day 1. Subjects will be discharged from
      the clinic on Day 2 (if stable as determined by the Investigator) and return for daily visits
      on Day 3 through Day 6 for a safety assessment and PK sampling. Subjects will undergo a
      follow-up visit on Day 7 (+1) and an end of study visit on Day 10 (+1).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of subjects with adverse events to assess safety and tolerability
time frame: Day 1 to Day 10 (+1)
description: Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).
measure: Clinical laboratory test values to assess safety and tolerability
time frame: Day -28 to Day 10 (+1)
description: Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.
measure: Vital signs to assess safety and tolerability
time frame: Day -28 to Day 10 (+1)
description: Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.
measure: Physician examination to assess safety and tolerability
time frame: Day -28 to Day 10 (+1)
description: Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.
measure: Measure of ECG to assess safety and tolerability
time frame: Day -28 to Day 10 (+1)
description: Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm. All subjects will undergo ECG testing.
measure: Maximum observed concentration (Cmax) of AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the resultant maximum plasma concentration (Cmax) will be measured in subjects with impaired renal function and normal renal function.
measure: Time to achieve maximum concentration (Tmax) of AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and time to maximum concentration (tmax) will be measured in subjects with impaired renal function and normal renal function.
measure: Apparent terminal elimination half life (t1/2 ) of AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and and apparent terminal elimination half-life (t1/2) will be measured in subjects with impaired renal function and normal renal function.
measure: Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-t will be measured in subjects with impaired renal function and normal renal function
measure: Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-inf will be measured in subjects with impaired renal function and normal renal function
measure: Apparent terminal elimination rate constant for AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the apparent terminal elimination rate constant will be measured in subjects with impaired renal function and normal renal function
measure: Oral clearance of AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral clearance will be measured in subjects with impaired renal function and normal renal function
measure: Oral volume of distribution of AT1001
time frame: Day 1 to Day 6
description: Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral volume of distribution will be measured in subjects with impaired renal function and normal renal function
arm group label: AT1001 150 mg
arm group type: Experimental
description: Each subject will receive a single oral dose of AT1001 150 mg administered orally with 240 mL room temperature water after at least a 4-hour fast
intervention type: Drug
intervention name: AT1001 150 mg
description: AT1001 150mg is available as a capsule
arm group label: AT1001 150 mg
other name: migalastat HCl
other name: GR181413A
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Monitor, Clinical Research
role: Study Director
affiliation: Amicus Therapeutics
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fabry Disease
mesh term: Renal Insufficiency