<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/NCT03797664</url>
  </required_header>
  <id_info>
    <org_study_id>CDX6114-004</org_study_id>
    <nct_id>NCT03797664</nct_id>
  </id_info>
  <brief_title>A Study of the Safety and Tolerability of CDX-6114 in Healthy Volunteers</brief_title>
  <official_title>A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of CDX-6114 Following Single, Ascending Oral Dose Administration to Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Codexis Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Codexis Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety and tolerability of an oral solution of&#xD;
      CDX-6114 when administered as a single dose in healthy volunteers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a second Phase 1, double-blind, placebo-controlled study in approximately 24 healthy&#xD;
      volunteers who are 18 to 55 years old. Three cohorts are planned each consisting of 8&#xD;
      subjects; the cohorts as planned are 7.5, 15.0 and 22.5 g of CDX-6114 (or matching placebo)&#xD;
      in oral solution. Increasing doses of CDX-6114 will be assessed sequentially un til the final&#xD;
      dose is evaluated or any of the stopping criteria are reached. Subjects will each receive&#xD;
      either a single dose of CDX-6114 or matching placebo, with food, and will then be followed&#xD;
      for a total of 22 days (3 weeks).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 14, 2018</start_date>
  <completion_date type="Actual">April 12, 2019</completion_date>
  <primary_completion_date type="Actual">April 12, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Dose-escalating, Randomized, Double-Blinded,. Placebo-Controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The incidence of treatment-emergent adverse events experienced by the subjects following oral administration of CDX-6114</measure>
    <time_frame>Up to 22 days after drug administartion</time_frame>
    <description>Will be measured by assessing the frequency and the nature of the AEs reported</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of CDX-6114</measure>
    <time_frame>Up to 24 hours after drug administration</time_frame>
    <description>Assessed by the serum levels of CDX-6114 following oral administration of CDX-6114</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics of CDX-6114</measure>
    <time_frame>Up to 24 hours after drug administration</time_frame>
    <description>Assessed by the plasma levels of phenylalanine and cinnamic acid following oral administration of CDX-6114</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Experimental: CDX-6114</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>7.5, 15.0 and 22.5g</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Comparator: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Phosphate Buffer Diluent Solution</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CDX-6114</intervention_name>
    <description>CDX-6114 will be administered as a single, oral dose solution at dose levels of 7.5, 15.0 and 22.5g</description>
    <arm_group_label>Experimental: CDX-6114</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Phosphate Buffer Diluent oral solution</description>
    <arm_group_label>Placebo Comparator: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male and female, non-smoking, subjects between the ages of 18 and 55 years,&#xD;
             inclusive, at the time of screening.&#xD;
&#xD;
          2. Have a body mass index (BMI) between 18.0 and 30.0 kg/m2 inclusive and weigh at least&#xD;
             50 kg and no more than 100 kg inclusive.&#xD;
&#xD;
          3. Good general health, as determined by an experienced physician based on a medical&#xD;
             evaluation including detailed medical history, full physical examination, including&#xD;
             blood pressure and pulse rate measurement, 12-lead electrocardiogram (ECG) and&#xD;
             clinical laboratory tests.&#xD;
&#xD;
          4. Male subjects and their female spouse/partner(s) who are of childbearing potential:&#xD;
&#xD;
               1. Must agree to stay abstinent (where abstinence is the preferred and usual&#xD;
                  life-style of the subject), starting at screening and continuing throughout the&#xD;
                  clinical study period, and for 90 days after study drug administration.&#xD;
&#xD;
                  Or&#xD;
&#xD;
               2. Must be using highly effective contraception consisting of 2 forms of birth&#xD;
                  control (1 of which must be a barrier method) starting at screening and&#xD;
                  continuing throughout the clinical study period, and for 90 days after study drug&#xD;
                  administration.&#xD;
&#xD;
               3. These requirements do not apply to participants in a same sex relationship.&#xD;
&#xD;
          5. Male subjects must agree not to donate sperm starting at screening and continuing&#xD;
             throughout the clinical study period, and for 90 days after study drug administration.&#xD;
&#xD;
          6. Female subjects of childbearing potential:&#xD;
&#xD;
               1. Must agree not to become pregnant during the clinical study period and for 30&#xD;
                  days after study drug administration.&#xD;
&#xD;
               2. Must have a negative serum pregnancy test at screening.&#xD;
&#xD;
               3. If heterosexually active, must agree to consistently use a form of highly&#xD;
                  effective birth control, in combination with a barrier method starting at&#xD;
                  screening and continuing throughout the clinical study period, and for 30 days&#xD;
                  after study drug administration&#xD;
&#xD;
                  Or&#xD;
&#xD;
               4. Must agree to stay abstinent, (where abstinence is the preferred and usual&#xD;
                  life-style of the subject), starting at screening and continuing throughout the&#xD;
                  clinical study period, and for 30 days after study drug administration.&#xD;
&#xD;
               5. These requirements do not apply to participants in a same sex relationship.&#xD;
&#xD;
          7. Female subjects of non-childbearing potential:&#xD;
&#xD;
               1. Must have a confirmed clinical history of sterility&#xD;
&#xD;
                  Or&#xD;
&#xD;
               2. Must be postmenopausal as defined as: amenorrhea for at least 1 year prior to&#xD;
                  screening and a laboratory confirmed serum follicle stimulating hormone (FSH)&#xD;
                  level ≥ 40mIU/mL.&#xD;
&#xD;
          8. Female subjects must agree not to breastfeed starting at screening and continuing&#xD;
             throughout the clinical study period, and for 90 days after study drug administration.&#xD;
&#xD;
          9. Female subjects must agree not to donate ova starting at screening and continuing&#xD;
             throughout the clinical study period, and for 90 days after study drug administration.&#xD;
&#xD;
         10. Subject must be competent to understand the nature of the study &amp; capable of giving&#xD;
             written informed consent. Be willing to report for the scheduled study visits and&#xD;
             communicate to study personnel about adverse events and concomitant medication use.&#xD;
&#xD;
         11. Subject must abstain from the following foods from 1 week prior to study drug&#xD;
             administration until the last PK sample has been obtained: grapefruit juice or&#xD;
             products, pomegranate juice or products, foods containing poppy seeds, and/or drinks&#xD;
             or foods containing quinine (e.g., tonic water) or Seville oranges (e.g., orange&#xD;
             marmalade).&#xD;
&#xD;
         12. Subject agrees not to participate in another interventional study while participating&#xD;
             in the present clinical study.&#xD;
&#xD;
             -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Female subject who has been pregnant within the 6 months prior to screening or&#xD;
             breastfeeding within the 3 months prior to screening.&#xD;
&#xD;
          2. Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease&#xD;
             (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies&#xD;
             and childhood asthma) at time of study drug administration.&#xD;
&#xD;
          3. Current or chronic history of gastrointestinal illness or conditions interfering with&#xD;
             normal gastrointestinal anatomy or motility. Examples include gastrointestinal bypass&#xD;
             surgery, cholecystectomy, partial or total gastrectomy, gastric band surgery, small&#xD;
             bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis,&#xD;
             irritable bowel syndrome (IBS) or celiac sprue.&#xD;
&#xD;
          4. Treatment with any anti-platelet and/or anticoagulant medication.&#xD;
&#xD;
          5. Evidence or history of specific food intolerance. Examples include gluten intolerance,&#xD;
             lactose intolerance, or dairy food intolerance or any food/ingredient included in the&#xD;
             protein breakfast.&#xD;
&#xD;
          6. A positive result, on screening, for serum hepatitis B surface antigen (HBsAg),&#xD;
             hepatitis A virus antibodies (HAV), hepatitis C virus antibodies (HCV) or antibodies&#xD;
             to human immunodeficiency virus type 1 (HIV-1) and/or type 2 (HIV-2).&#xD;
&#xD;
          7. A positive pre-study drug/alcohol screen. However, there is the option to re-screen&#xD;
             during the screening period at the discretion of the PI or delegate in the case of a&#xD;
             positive pre-study drug screen for a prescribed medication e.g. codeine.&#xD;
&#xD;
          8. Subject has a history of drinking &gt; 21 units of alcohol/week for male subjects or &gt; 14&#xD;
             units of alcohol/week for female subjects within the 3 months prior to screening.&#xD;
&#xD;
          9. Subject has a history of regular smoking (daily or most days in a week) or the use of&#xD;
             nicotine products (3 or more nicotine-containing products) within the 6 months prior&#xD;
             to screening.&#xD;
&#xD;
         10. Subjects who show evidence of use of any recreational drugs of abuse on testing or&#xD;
             recent history (within the 3 months prior to screening).&#xD;
&#xD;
         11. Subject has a pulse rate &lt;40 or &gt; 100 bpm; mean systolic blood pressure (SBP) &gt; 140&#xD;
             mmHg; mean diastolic blood pressure (DBP) &gt; 90 mmHg at screening. Repeat measurements&#xD;
             are allowed at the discretion of the PI or delegate.&#xD;
&#xD;
         12. Subject has any clinically significant abnormalities at screening in rhythm,&#xD;
             conduction or morphology of the resting ECG and any clinically significant&#xD;
             abnormalities in the 12-lead ECG, as considered by the Investigator, that may&#xD;
             interfere with the interpretation of QTc interval changes including abnormal ST-T wave&#xD;
             morphology.&#xD;
&#xD;
         13. Subject has prolonged QTcF (QT interval corrected for heart rate using Fridericia's&#xD;
             formula) &gt; 450 ms for male subjects or &gt; 470 ms for female subjects, or shortened QTcF&#xD;
             &lt; 300 ms or a family history of prolonged QT syndrome, at screening.&#xD;
&#xD;
         14. Subject has any clinically significant abnormalities in clinical chemistry,&#xD;
             hematology, or urinalysis at screening as judged by the Investigator, including:&#xD;
             Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase&#xD;
             (ALP), gamma glutamyl transferase (GGT) or Total bilirubin (TBL) more than 1.5 times&#xD;
             the Upper Limit of Normal (ULN).&#xD;
&#xD;
         15. Plasma donation within the 14 days prior to screening or any whole blood&#xD;
             donation/significant blood loss &gt; 500 mL during the 3 months prior to screening.&#xD;
&#xD;
         16. Treatment with any Investigational Drug or Device/Treatment within the 30 days prior&#xD;
             to the administration of study drug.&#xD;
&#xD;
         17. Use of any prescribed or non-prescribed medication including, herbal and dietary&#xD;
             supplements, antacids, analgesics (other than oral contraceptives, paracetamol or&#xD;
             multi-vitamins) during the two weeks prior to the administration of the study drug, or&#xD;
             up to a minimum of 5 times the half-life of the medication if it has a long half-life.&#xD;
&#xD;
         18. Previous treatment with CDX-6114 active study drug (but not placebo) in study&#xD;
             CDX6114-001.&#xD;
&#xD;
         19. Known allergy or adverse reaction history to any of the oral dose formulation&#xD;
             components e.g. mannitol&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sam Salman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Linear Clinical Services</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Linear Clinical Services</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>August 2, 2021</last_update_submitted>
  <last_update_submitted_qc>August 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03797664
org study id: CDX6114-004
nct id: NCT03797664
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to assess the safety and tolerability of an oral solution of
      CDX-6114 when administered as a single dose in healthy volunteers
This is a second Phase 1, double-blind, placebo-controlled study in approximately 24 healthy
      volunteers who are 18 to 55 years old. Three cohorts are planned each consisting of 8
      subjects; the cohorts as planned are 7.5, 15.0 and 22.5 g of CDX-6114 (or matching placebo)
      in oral solution. Increasing doses of CDX-6114 will be assessed sequentially un til the final
      dose is evaluated or any of the stopping criteria are reached. Subjects will each receive
      either a single dose of CDX-6114 or matching placebo, with food, and will then be followed
      for a total of 22 days (3 weeks).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Dose-escalating, Randomized, Double-Blinded,. Placebo-Controlled
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-Blind
measure: The incidence of treatment-emergent adverse events experienced by the subjects following oral administration of CDX-6114
time frame: Up to 22 days after drug administartion
description: Will be measured by assessing the frequency and the nature of the AEs reported
measure: Pharmacokinetics of CDX-6114
time frame: Up to 24 hours after drug administration
description: Assessed by the serum levels of CDX-6114 following oral administration of CDX-6114
measure: Pharmacodynamics of CDX-6114
time frame: Up to 24 hours after drug administration
description: Assessed by the plasma levels of phenylalanine and cinnamic acid following oral administration of CDX-6114
arm group label: Experimental: CDX-6114
arm group type: Experimental
description: 7.5, 15.0 and 22.5g
arm group label: Placebo Comparator: Placebo
arm group type: Placebo Comparator
description: Phosphate Buffer Diluent Solution
intervention type: Drug
intervention name: CDX-6114
description: CDX-6114 will be administered as a single, oral dose solution at dose levels of 7.5, 15.0 and 22.5g
arm group label: Experimental: CDX-6114
intervention type: Drug
intervention name: Placebo
description: Phosphate Buffer Diluent oral solution
arm group label: Placebo Comparator: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sam Salman
role: Principal Investigator
affiliation: Linear Clinical Services
facility: 
country: Australia
responsible party type: Sponsor
sharing ipd: No