<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/NCT04446507</url>
  </required_header>
  <id_info>
    <org_study_id>SARO.19.004</org_study_id>
    <nct_id>NCT04446507</nct_id>
  </id_info>
  <brief_title>A Pharmacokinetic Study of Saroglitazar Magnesium in Subjects With Severe Renal Impairment and Normal Renal Function</brief_title>
  <official_title>A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Saroglitazar Magnesium in Participants With Normal Renal Function and Participants With Severe Renal Impairment.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zydus Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zydus Therapeutics Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a Phase 1, Open-label Study of Participants with Normal Renal Function and&#xD;
      Participants with Sever Renal Impairment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 32 participants will be enrolled:&#xD;
&#xD;
      Group 1 (Severe renal impairment not on HD, eGFR &lt;30) - 16 subjects Subjects will be enrolled&#xD;
      and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by&#xD;
      another 8 subjects who will receive 4 mg dose).&#xD;
&#xD;
      Group 2 (Normal renal function eGFR ≥90) - 16 subjects Subjects in this group will be matched&#xD;
      according to age (± 10 years), sex, and weight (± 10 kg) with participants in Group 1 (Severe&#xD;
      renal impairment not on HD) on a one to one basis based on demographic characteristic. In&#xD;
      this group, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium&#xD;
      and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Anticipated">August 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2024</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>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC from time zero to infinity (AUC0-∞)</measure>
    <time_frame>Before dosing on Day 1 through Day 7</time_frame>
    <description>The area under the plasma concentration versus time curve from zero to infinity will be calculated by adding Ct/Kel to AUCt, where Ct is the last quantifiable concentration and Kel is the elimination rate constant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC from time zero to the last quantifiable concentration (AUC0-t)</measure>
    <time_frame>Before dosing on Day 1 through Day 7</time_frame>
    <description>The area under the plasma concentration versus time curve will be calculated using the linear trapezoidal rule from the zero time point to the last quantifiable concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>Before dosing on Day 1 through Day 7</time_frame>
    <description>Maximum measured plasma concentration over the time span specified.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax</measure>
    <time_frame>Before dosing on Day 1 through Day 7</time_frame>
    <description>Time of the maximum measured plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>t1/2</measure>
    <time_frame>Before dosing on Day 1 through Day 7</time_frame>
    <description>The half-life will be calculated by the equation tHalf = 0.693/ Kel. Kel (The terminal elimination rate constant) will be obtained from the slope of the line, fitted by linear least squares regression, through the terminal points of the natural log of the concentration versus time plot for these points</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CL/F</measure>
    <time_frame>Before dosing on Day 1 through Day 7</time_frame>
    <description>Clearance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vz/F</measure>
    <time_frame>Before dosing on Day 1 through Day 7</time_frame>
    <description>Volume of distribution</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Urine Pharmacokinetic: Ae</measure>
    <time_frame>Before dosing on Day 1 through Day 5</time_frame>
    <description>Amount of drug excreted during each collection interval</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of AEs</measure>
    <time_frame>Before dosing on Day 1 through Day 12</time_frame>
    <description>Incidence and severity of AEs as a measure of safety and tolerability will be measured and reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unbound Fraction</measure>
    <time_frame>Day 1</time_frame>
    <description>Unbound fraction in plasma of Saroglitazar</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unbound concentration</measure>
    <time_frame>Day 1</time_frame>
    <description>Unbound concentration in plasma of Saroglitazar</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">32</enrollment>
  <condition>Renal Impairment</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in severe renal impairment group will be enrolled and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by another 8 subjects who will receive 4 mg dose).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects (Normal renal function eGFR ≥90) will be matched according to age (± 10 years), sex, and weight (± 10 kg) with participants in Group 1 (Severe renal impairment not on HD) on a one to one basis based on demographic characteristic. Here, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saroglitazar magnesium</intervention_name>
    <description>1 dose of 2mg and 4 mg Saroglitazar magnesium will be given to subjects on Day 1</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>not any</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ability to comprehend and willingness to sign a written ICF for the study.&#xD;
&#xD;
          2. Male or female subjects aged 18 to 80 years (inclusive) at the time of signing the&#xD;
             ICF.&#xD;
&#xD;
          3. Participants will be classified at screening by renal function as determined by the&#xD;
             modification of diet in renal disease (MDRD) formula for estimated glomerular&#xD;
             filtration rate (eGFR) in subjects with chronic kidney disease (CKD). Classification&#xD;
             will be repeated at Day -1, if the renal function classification for the participant&#xD;
             is not the same at the two time points, enrollment of the participant will be based on&#xD;
             eGFR at screening.&#xD;
&#xD;
          4. Group 2 (Normal renal function) subjects, should be in good health as determined by no&#xD;
             clinically significant deviations from normal for medical history, physical&#xD;
             examination, vital signs, 12 lead electrocardiograms (ECGs), or laboratory&#xD;
             examinations at screening or Day-1.&#xD;
&#xD;
          5. Group 1 (Severe renal impairment not on HD, eGFR &lt;30) subjects, may have medical&#xD;
             findings consistent with their degree of renal impairment, as determined by medical&#xD;
             history, physical examination, vital signs, ECGs, and clinical laboratory examinations&#xD;
             at screening and Day -1. Participants are eligible if abnormal findings are considered&#xD;
             not clinically significant by the Investigator.&#xD;
&#xD;
          6. Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.&#xD;
&#xD;
          7. Females must be non-pregnant, non-lactating and of non-childbearing potential or using&#xD;
             highly efficient contraception for the full duration of the study. Female of&#xD;
             childbearing potential and Males must agree to use contraception for the full duration&#xD;
             of the study.&#xD;
&#xD;
          8. Ability to swallow and retain oral medication.&#xD;
&#xD;
          9. Laboratory test values within normal limits or considered not clinically significant&#xD;
             by the investigator for subjects in Group 2 with normal renal function. Must have eGFR&#xD;
             ≥ 90 by MDRD calculation.&#xD;
&#xD;
         10. Group 2 patients with normal renal function must match in age (± 10 years), sex, and&#xD;
             weight (± 10 kg) with severe renal impairment participants in the Group 1.&#xD;
&#xD;
         11. Laboratory test values for severe renal impairment subjects must be clinically&#xD;
             acceptable to the Investigator and meet all of the following parameters at screening:&#xD;
&#xD;
               1. ALT value ≤ 3 × ULN&#xD;
&#xD;
               2. AST value ≤ 3 × ULN&#xD;
&#xD;
               3. Absolute neutrophil count (ANC) ≥ 750/mm3&#xD;
&#xD;
               4. Platelets ≥ 50,000/mm3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any significant, unstable medical condition or other instability that would prevent&#xD;
             the subject from participating in the study as determined by the investigator or&#xD;
             designee.&#xD;
&#xD;
          2. History of malignancy of any type in the last 3 years of screening, with the exception&#xD;
             of the following: in situ cervical or breast cancer or surgically excised non-melanoma&#xD;
             skin cancers (i.e. basal cell or squamous cell carcinoma).&#xD;
&#xD;
          3. History of stomach or intestinal surgery or resection within the six months prior to&#xD;
             screening that would potentially alter absorption and/or excretion of orally&#xD;
             administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair&#xD;
             will be allowed).&#xD;
&#xD;
          4. History of any significant drug allergy (such as anaphylaxis) deemed clinically&#xD;
             relevant by the investigator.&#xD;
&#xD;
          5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of asymptomatic gallstones) or other hepatic abnormalities that in&#xD;
             the opinion of the investigator would preclude the subject from participation in the&#xD;
             study.&#xD;
&#xD;
          6. Any major surgery within 3 months of screening.&#xD;
&#xD;
          7. Donation of blood or blood products within 3 months prior to screening.&#xD;
&#xD;
          8. Blood transfusion within 2 weeks of Day -1.&#xD;
&#xD;
          9. Current active infectious disease requiring systemic antibiotic, antifungal, or&#xD;
             antiviral treatment.&#xD;
&#xD;
         10. Use or intend to use any medications/products known to alter drug absorption,&#xD;
             metabolism, or elimination processes, including St. John's Wort, within 21 days prior&#xD;
             to screening, unless deemed acceptable by the Investigator.&#xD;
&#xD;
         11. Receiving or has received any investigational drug within the 30 days or 5 halflives&#xD;
             (whichever is longer), before receiving Saroglitazar Magnesium.&#xD;
&#xD;
         12. Group 2 (Normal renal function) subjects, who have a history of renal disease or renal&#xD;
             injury as indicated by an abnormal BUN or creatinine at screening or Day-1.&#xD;
&#xD;
         13. Group 1 (Severe renal impairment) subjects, who have had a change in renal disease&#xD;
             status within 30 days of screening, as documented by the participant's medical history&#xD;
             and deemed clinically significant by the investigator.&#xD;
&#xD;
         14. For healthy renal function subjects, QT interval corrected for heart rate using&#xD;
             Fridericia's method (QTcF) &gt; 450 msec, confirmed by repeat measurement. In renal&#xD;
             impaired subjects QTcF &gt; 500 msec, confirmed by repeat measurement; no second or third&#xD;
             degree AV block.&#xD;
&#xD;
         15. Group 1 subjects, who use or intend to use any over-the-counter (vitamins, minerals,&#xD;
             and phytotherapeutic/herbal/plant-derived preparations) or prescription medications&#xD;
             within 30 days or 5 half-lives (whichever is longer) prior to enrollment, with the&#xD;
             exception of hormone replacement therapy and therapies for renal disease and&#xD;
             treatments of associated disorders that have been stable for at least 30 days prior to&#xD;
             screening and until Day 1, unless deemed acceptable by the investigator (or designee).&#xD;
&#xD;
         16. Group 2 Subjects who have taken any prescription medications or over-the counter&#xD;
             medications, including herbal products, within 14 days prior to start of study drug&#xD;
             dosing, with the exception of vitamins, acetaminophen, hormonal contraceptive&#xD;
             medications and/or any other over-the-counter product approved by the investigator.&#xD;
&#xD;
         17. Positive alcohol breath test at the time of check-in or those subjects who have&#xD;
             current alcohol or substance abuse judged by the investigator to potentially interfere&#xD;
             with subject compliance or subject safety.&#xD;
&#xD;
         18. Positive test for drugs of abuse at screening or admission.&#xD;
&#xD;
         19. Any subject with poor peripheral venous access.&#xD;
&#xD;
         20. Human immunodeficiency virus (HIV) type 1 antibody, HBsAg or HCV-Ab positive at&#xD;
             screening.&#xD;
&#xD;
         21. Additional exclusion criteria for Severe Renal Impairment subjects:&#xD;
&#xD;
               1. History of nephrectomy or renal transplant&#xD;
&#xD;
               2. Any type of dialysis within 3 months prior to screening&#xD;
&#xD;
               3. Electrolyte abnormality or other screening laboratory value deemed clinically&#xD;
                  significant by investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Eric Lawitz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>American Research Corporation @ Texas Liver Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dr. Deven V. Parmar, MD</last_name>
    <phone>+971-43998280</phone>
    <phone_ext>121</phone_ext>
    <email>deven.parmar@zydusdiscovery.ae</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dr. Farheen A. Shaikh</last_name>
    <phone>+971-43998280</phone>
    <phone_ext>105</phone_ext>
    <email>Farheen.arifahmed@zydusdiscovery.ae</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>American Research Corporation @ Texas Liver Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dr. Eric Lawitz, MD</last_name>
      <phone>210-253-3426</phone>
      <email>lawitz@txliver.com</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>August 6, 2023</last_update_submitted>
  <last_update_submitted_qc>August 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</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>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/NCT04446507
org study id: SARO.19.004
nct id: NCT04446507
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This will be a Phase 1, Open-label Study of Participants with Normal Renal Function and
      Participants with Sever Renal Impairment.
A total of 32 participants will be enrolled:

      Group 1 (Severe renal impairment not on HD, eGFR <30) - 16 subjects Subjects will be enrolled
      and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by
      another 8 subjects who will receive 4 mg dose).

      Group 2 (Normal renal function eGFR ≥90) - 16 subjects Subjects in this group will be matched
      according to age (± 10 years), sex, and weight (± 10 kg) with participants in Group 1 (Severe
      renal impairment not on HD) on a one to one basis based on demographic characteristic. In
      this group, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium
      and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUC from time zero to infinity (AUC0-∞)
time frame: Before dosing on Day 1 through Day 7
description: The area under the plasma concentration versus time curve from zero to infinity will be calculated by adding Ct/Kel to AUCt, where Ct is the last quantifiable concentration and Kel is the elimination rate constant.
measure: AUC from time zero to the last quantifiable concentration (AUC0-t)
time frame: Before dosing on Day 1 through Day 7
description: The area under the plasma concentration versus time curve will be calculated using the linear trapezoidal rule from the zero time point to the last quantifiable concentration.
measure: Cmax
time frame: Before dosing on Day 1 through Day 7
description: Maximum measured plasma concentration over the time span specified.
measure: Tmax
time frame: Before dosing on Day 1 through Day 7
description: Time of the maximum measured plasma concentration.
measure: t1/2
time frame: Before dosing on Day 1 through Day 7
description: The half-life will be calculated by the equation tHalf = 0.693/ Kel. Kel (The terminal elimination rate constant) will be obtained from the slope of the line, fitted by linear least squares regression, through the terminal points of the natural log of the concentration versus time plot for these points
measure: CL/F
time frame: Before dosing on Day 1 through Day 7
description: Clearance
measure: Vz/F
time frame: Before dosing on Day 1 through Day 7
description: Volume of distribution
measure: Urine Pharmacokinetic: Ae
time frame: Before dosing on Day 1 through Day 5
description: Amount of drug excreted during each collection interval
measure: Incidence of AEs
time frame: Before dosing on Day 1 through Day 12
description: Incidence and severity of AEs as a measure of safety and tolerability will be measured and reported.
measure: Unbound Fraction
time frame: Day 1
description: Unbound fraction in plasma of Saroglitazar
measure: Unbound concentration
time frame: Day 1
description: Unbound concentration in plasma of Saroglitazar
arm group label: Group 1
arm group type: Experimental
description: Subjects in severe renal impairment group will be enrolled and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by another 8 subjects who will receive 4 mg dose).
arm group label: Group 2
arm group type: Experimental
description: Subjects (Normal renal function eGFR ≥90) will be matched according to age (± 10 years), sex, and weight (± 10 kg) with participants in Group 1 (Severe renal impairment not on HD) on a one to one basis based on demographic characteristic. Here, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium.
intervention type: Drug
intervention name: Saroglitazar magnesium
description: 1 dose of 2mg and 4 mg Saroglitazar magnesium will be given to subjects on Day 1
arm group label: Group 1
arm group label: Group 2
other name: not any
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Dr. Eric Lawitz, MD
role: Principal Investigator
affiliation: American Research Corporation @ Texas Liver Institute
last name: Dr. Deven V. Parmar, MD
phone: +971-43998280
phone ext: 121
email: deven.parmar@zydusdiscovery.ae
last name: Dr. Farheen A. Shaikh
phone: +971-43998280
phone ext: 105
email: Farheen.arifahmed@zydusdiscovery.ae
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Renal Insufficiency