xml: <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/NCT05965414</url>
    </required_header>
    <id_info>
      <org_study_id>ATI-CS-001</org_study_id>
      <secondary_id>1R44AG076299</secondary_id>
      <nct_id>NCT05965414</nct_id>
    </id_info>
    <brief_title>Safety and Pharmacokinetics of Single Ascending Doses and Multiple Ascending Doses of CS6253 in Healthy Volunteers</brief_title>
    <official_title>A Phase 1 Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Pharmacokinetics of Single Ascending Doses and Multiple Ascending Doses of CS6253 in Healthy Volunteers and in APOE4 Carriers</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Artery Therapeutics, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute on Aging (NIA)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>Artery Therapeutics, Inc.</source>
    <oversight_info>
      <has_dmc>Yes</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>
        -  Phase 1A SAD: Five or more cohorts of 8 healthy volunteers (HVs) will receive a single&#xD;
             IV bolus injection of study drug or placebo. The first 4 cohorts will be male only. The&#xD;
             last cohort will be repeated with the max safe dose of the previous cohorts in healthy&#xD;
             elderly subjects (male and female of non childbearing potential, &gt; 50years)&#xD;
  &#xD;
          -  Phase 1B MAD: Two or more cohorts of 8 male and female HVs will receive multiple (4) IV&#xD;
             bolus injections of study drug or placebo every 72 hours.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a randomized, double-blind, placebo-controlled study in HV and in APOE4 carriers.&#xD;
  &#xD;
        Phase 1A Single Ascending Dose (SAD): In 5 or more sequential SAD cohorts of 8 (6 active:2&#xD;
        placebo) HVs a single IV bolus injection (CS6253 1, 2.4, 6, and 10 mg/kg or placebo) will be&#xD;
        administered and PK, safety, and biomarkers will be assessed. The first 4 cohorts will&#xD;
        include males only. In the fifth cohort 8 (6 active:2 placebo) subjects, male and female of&#xD;
        non-childbearing potential and at least 50 years old, will be administered CS6253 at equal to&#xD;
        or lower doses than the maximum safe SAD dose in HV.&#xD;
  &#xD;
        CSF will not be collected in the first 2 SAD cohorts. In the following cohorts, CSF will be&#xD;
        collected before dosing and over 24 hours after dosing. Additional cohorts may be added as&#xD;
        needed and deemed safe and appropriate by the Data Safety Monitoring Board (DSMB).&#xD;
  &#xD;
        Phase 1B Multiple Ascending Dose (MAD): In 2 or more sequential MAD cohorts of 8 (6 active:2&#xD;
        placebo) male and female HVs at least 50 years old on average ≥ 3/sex/cohort; ≥ 4 APOE4&#xD;
        carriers/cohort, will be administered multiple IV bolus injections. Cohort 1 will be&#xD;
        administered CS6253 at 75% of the maximum safe SAD dose in subjects at least 50 years old or&#xD;
        placebo, and if no Treatment Emerging Adverse Events (TEAEs), in Cohort 2 at 100% of the&#xD;
        maximum safe SAD dose or placebo will be administered every 72 hours x 4 doses and PK,&#xD;
        safety, and biomarkers will be assessed. Plasma PK will be assessed after first and fourth&#xD;
        dose in all cohorts. CSF will be collected before dosing and over 24 hours in conjunction&#xD;
        with the fourth dose. Cohorts of 8 subjects (6 active:2 placebo) may be added at doses equal&#xD;
        to or lower than the maximum safe MAD dose to further explore CS6253 brain exposure and&#xD;
        Pharmacodynamics (PD) dependency on APOE4 isoform and sex.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 4, 2023</start_date>
    <completion_date type="Anticipated">September 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</primary_completion_date>
    <phase>Early 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>SAD:&#xD;
  5 cohorts 8 of healthy volunteers each will receive single ascending doses of either study drug or placebo (6 active:2 placebo).&#xD;
  MAD:&#xD;
  2 or more cohorts 8 of healthy male and female volunteers each will receive single ascending doses of either study drug or placebo (6 active:2 placebo). The subjects will be stratified on their APOE4 status. Each cohort needs to have at least 4 APOE4 carriers.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>Neither the investigator nor the subject will know who has received the study drug or the placebo, The injections will be prepared by an unblinded pharmacist according to the randomization list.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Safety and tolerability of CS6253</measure>
      <time_frame>SAD: After dosing and until 72 hours after dosing; MAD: After dosing until day 13 (72 hours after the last dosing on day 10)</time_frame>
      <description>All treatment emerging Adverse Events (TAEs) will be recorded until the SAD: Day 4 and MAD: Day 13</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Plasma: AUC0-last</measure>
      <time_frame>Pharmacokinetics (PK) samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:</time_frame>
      <description>Area under the concentration-time curve until the last quantifiable concentration</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Plasma: AUC0-inf</measure>
      <time_frame>PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:</time_frame>
      <description>Area under the concentration time curve from time 0 extrapolated to infinity</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Plasma: Cmax</measure>
      <time_frame>PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:</time_frame>
      <description>Maximum observed plasma concentration (eg C0)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Plasma: Kel</measure>
      <time_frame>PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:</time_frame>
      <description>Terminal elimination rate constant</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Plasma: t1/2</measure>
      <time_frame>PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:</time_frame>
      <description>Terminal elimination half-life</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Plasma: Clearance (CL/F)</measure>
      <time_frame>PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:</time_frame>
      <description>Apparent clearance</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Plasma: Vd/F</measure>
      <time_frame>PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:</time_frame>
      <description>Apparent volume of distribution</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-Cerebrospinal Fluid (CSF): AUC0-last</measure>
      <time_frame>PK samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.</time_frame>
      <description>In cohorts 3-5:Area under the concentration-time curve in CSF until the last quantifiable concentration</description>
    </primary_outcome>
    <primary_outcome>
      <measure>SAD-CSF: Cmax</measure>
      <time_frame>PK samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.</time_frame>
      <description>In cohorts 3-5:Maximum observed CSF concentration (eg C0)concentration</description>
    </primary_outcome>
    <primary_outcome>
      <measure>MAD-Plasma: AUC0-last</measure>
      <time_frame>PK samples will be collected after the first and fourth doses (Day 1 and Day 10) at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hours postdose.</time_frame>
      <description>Area under the concentration-time curve until the last quantifiable concentration</description>
    </primary_outcome>
    <primary_outcome>
      <measure>MAD-Plasma: Cmax</measure>
      <time_frame>PK samples will be collected after the first and fourth doses (Day 1 and Day 10) at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hours postdose.</time_frame>
      <description>Maximum observed plasma concentration (eg C0)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>MAD-CSF:AUC0-last</measure>
      <time_frame>CSF collection by lumbar puncture (LP) will be performed before the first dose. At the fourth dose, on Day 10, serial CSF samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.</time_frame>
      <description>Area under the concentration-time curve until the last quantifiable concentration</description>
    </primary_outcome>
    <primary_outcome>
      <measure>MAD-CSF: Cmax</measure>
      <time_frame>CSF collection by lumbar puncture (LP) will be performed before the first dose. At the fourth dose, on Day 10, serial CSF samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.</time_frame>
      <description>Maximum observed CSF concentration (eg C0)</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">64</enrollment>
    <condition>Alzheimer's Disease</condition>
    <arm_group>
      <arm_group_label>CS6253 Solution for Injection</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>SAD: Single ascending doses: CS6253 Solution for Injection dosing, 50 mg/mL, will be weight based and provided from single use 2 mL vials containing approximately 100 mg CS6253 in phosphate buffered saline (PBS) solution&#xD;
  MAD: Multiple ascending doses (4x every 72 hours): CS6253 Solution for Injection dosing, 50 mg/mL, will be weight based and provided from single use 2 mL vials containing approximately 100 mg CS6253 in phosphate buffered saline (PBS) solution</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>SAD and MAD: Placebo control will be provided from vials containing physiological saline for injection in an equal amount as necessary for the active arm.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>CS6253 Solution for Injection</intervention_name>
      <description>Solution for intra-venous injection, 50mg CS6253 /mL. Single-use vials containing 100 mg CS6253 (2 mL of 50 mg/mL concentration)</description>
      <arm_group_label>CS6253 Solution for Injection</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Physiological saline solution for intra-venous injection</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male HVs at least 18 years old.&#xD;
  &#xD;
            2. a) Cohort 5 only: Male and female HVs at least 50 years old and if female be of&#xD;
               non-childbearing potential, i.e. meet at least one of the following criteria:&#xD;
               postsurgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation)&#xD;
               or postmenopausal (amenorrheic for at least 2 years and a serum follicle-stimulating&#xD;
               hormone (FSH) &gt; 30 IU/L).&#xD;
  &#xD;
               b) If subject is male, must be willing to use acceptable contraception from Day 1&#xD;
               until 30 days after the last dose of study drug.&#xD;
  &#xD;
            3. The subject has a body mass index (BMI) within 18-32 kg/m² (inclusive).&#xD;
  &#xD;
            4. The subject is in reasonably good health as determined by medical history and physical&#xD;
               examination and clinical laboratory tests.&#xD;
  &#xD;
            5. The subject is willing and able to speak, read, and understand Spanish and give signed&#xD;
               informed consent.&#xD;
  &#xD;
            6. The subject must agree to comply with a lumbar catheterization and collection of blood&#xD;
               and CSF samples (SAD Cohorts 3-5 only and MAD cohorts).&#xD;
  &#xD;
            7. The subject is willing and able to comply with all testing and requirements defined in&#xD;
               the protocol.&#xD;
  &#xD;
            8. The subject is willing, deemed compliant, and able to remain at the Clinical Research&#xD;
               Unit (CRU) for the duration of the confinement period and return for all outpatient&#xD;
               visits.&#xD;
  &#xD;
          Phase 1B MAD&#xD;
  &#xD;
          The eligibility criteria for the Phase 1B MAD study are the same as described for Phase 1A&#xD;
          SAD, with the following exceptions:&#xD;
  &#xD;
            1. At least 50 years old and female need to be of non-childbearing potential&#xD;
  &#xD;
            2. Known to have at least 1 APOE4 allele (homozygous or heterozygous). Note: this&#xD;
               criterion applies to on average for the MAD at least 4 APOE4 subjects per cohort.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Subjects who meet any of the following criteria will not be enrolled:&#xD;
  &#xD;
            1. The subject has any clinically significant deviations from normal in physical&#xD;
               examination, ECG, or clinical laboratory tests, as determined by the investigator.&#xD;
  &#xD;
            2. The subject has an increased bleeding risk or is treated with anti-coagulation&#xD;
               therapies including but not limited to aspirin, coumarin, warfarin and heparin.&#xD;
  &#xD;
            3. The subject has had a clinically significant illness within 30 days of check-in, as&#xD;
               determined by the investigator.&#xD;
  &#xD;
            4. The subject has a history of significant neurological, hepatic, renal, endocrine,&#xD;
               cardiovascular, gastrointestinal, pulmonary, or metabolic disease.&#xD;
  &#xD;
            5. History of Type 2 diabetes mellitus or hemoglobin A1c (HbA1c) &gt; 7%.&#xD;
  &#xD;
            6. Fasting triglycerides &gt; 400 mg/dL&#xD;
  &#xD;
            7. Estimated glomerular filtration rate (eGFR) &lt; 30 mL/min/1.73 m2 (Cockcroft-Gault&#xD;
               formula)&#xD;
  &#xD;
            8. The subject has changed the frequency or dose of chronic medication within the last 8&#xD;
               weeks.&#xD;
  &#xD;
            9. The subject has a history of substance abuse or a positive alcohol or urine drug&#xD;
               screen at screening or at check-in.&#xD;
  &#xD;
           10. The subject has a positive serum hepatitis B surface antigen or positive&#xD;
               anti-hepatitis C virus test at the Screening Visit.&#xD;
  &#xD;
           11. Have positive test results for, or evidence of active infection with, human&#xD;
               immunodeficiency virus type 1 or 2, or hepatitis B, or C.&#xD;
  &#xD;
           12. The subject has received an investigational drug within 30 days of Check-in.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Alberto M. Borobia Perez, MD, Ass.Prof</last_name>
      <role>Principal Investigator</role>
      <affiliation>Universidad Autónoma de Madrid, Farmacología y Terapéutica / Facultad de Medicina</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nikola Helmberg, PhD</last_name>
      <phone>+4366488397558</phone>
      <email>nhelmberg@neuroscios.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Barbara Fridrich</last_name>
      <phone>+4366488869909</phone>
      <email>bfridrich@neuroscios.com</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>January 26, 2023</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 20, 2023</last_update_submitted>
    <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 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>Alzheimer Disease</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>No individual participant data will be shared</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05965414
  org study id: ATI-CS-001
  secondary id: 1R44AG076299
  nct id: NCT05965414
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  -  Phase 1A SAD: Five or more cohorts of 8 healthy volunteers (HVs) will receive a single
             IV bolus injection of study drug or placebo. The first 4 cohorts will be male only. The
             last cohort will be repeated with the max safe dose of the previous cohorts in healthy
             elderly subjects (male and female of non childbearing potential, > 50years)
  
          -  Phase 1B MAD: Two or more cohorts of 8 male and female HVs will receive multiple (4) IV
             bolus injections of study drug or placebo every 72 hours.
  This is a randomized, double-blind, placebo-controlled study in HV and in APOE4 carriers.
  
        Phase 1A Single Ascending Dose (SAD): In 5 or more sequential SAD cohorts of 8 (6 active:2
        placebo) HVs a single IV bolus injection (CS6253 1, 2.4, 6, and 10 mg/kg or placebo) will be
        administered and PK, safety, and biomarkers will be assessed. The first 4 cohorts will
        include males only. In the fifth cohort 8 (6 active:2 placebo) subjects, male and female of
        non-childbearing potential and at least 50 years old, will be administered CS6253 at equal to
        or lower doses than the maximum safe SAD dose in HV.
  
        CSF will not be collected in the first 2 SAD cohorts. In the following cohorts, CSF will be
        collected before dosing and over 24 hours after dosing. Additional cohorts may be added as
        needed and deemed safe and appropriate by the Data Safety Monitoring Board (DSMB).
  
        Phase 1B Multiple Ascending Dose (MAD): In 2 or more sequential MAD cohorts of 8 (6 active:2
        placebo) male and female HVs at least 50 years old on average ≥ 3/sex/cohort; ≥ 4 APOE4
        carriers/cohort, will be administered multiple IV bolus injections. Cohort 1 will be
        administered CS6253 at 75% of the maximum safe SAD dose in subjects at least 50 years old or
        placebo, and if no Treatment Emerging Adverse Events (TEAEs), in Cohort 2 at 100% of the
        maximum safe SAD dose or placebo will be administered every 72 hours x 4 doses and PK,
        safety, and biomarkers will be assessed. Plasma PK will be assessed after first and fourth
        dose in all cohorts. CSF will be collected before dosing and over 24 hours in conjunction
        with the fourth dose. Cohorts of 8 subjects (6 active:2 placebo) may be added at doses equal
        to or lower than the maximum safe MAD dose to further explore CS6253 brain exposure and
        Pharmacodynamics (PD) dependency on APOE4 isoform and sex.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: SAD:
  5 cohorts 8 of healthy volunteers each will receive single ascending doses of either study drug or placebo (6 active:2 placebo).
  MAD:
  2 or more cohorts 8 of healthy male and female volunteers each will receive single ascending doses of either study drug or placebo (6 active:2 placebo). The subjects will be stratified on their APOE4 status. Each cohort needs to have at least 4 APOE4 carriers.
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: Neither the investigator nor the subject will know who has received the study drug or the placebo, The injections will be prepared by an unblinded pharmacist according to the randomization list.
  measure: Safety and tolerability of CS6253
  time frame: SAD: After dosing and until 72 hours after dosing; MAD: After dosing until day 13 (72 hours after the last dosing on day 10)
  description: All treatment emerging Adverse Events (TAEs) will be recorded until the SAD: Day 4 and MAD: Day 13
  measure: SAD-Plasma: AUC0-last
  time frame: Pharmacokinetics (PK) samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:
  description: Area under the concentration-time curve until the last quantifiable concentration
  measure: SAD-Plasma: AUC0-inf
  time frame: PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:
  description: Area under the concentration time curve from time 0 extrapolated to infinity
  measure: SAD-Plasma: Cmax
  time frame: PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:
  description: Maximum observed plasma concentration (eg C0)
  measure: SAD-Plasma: Kel
  time frame: PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:
  description: Terminal elimination rate constant
  measure: SAD-Plasma: t1/2
  time frame: PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:
  description: Terminal elimination half-life
  measure: SAD-Plasma: Clearance (CL/F)
  time frame: PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:
  description: Apparent clearance
  measure: SAD-Plasma: Vd/F
  time frame: PK samples will be collected at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours postdose; MAD:
  description: Apparent volume of distribution
  measure: SAD-Cerebrospinal Fluid (CSF): AUC0-last
  time frame: PK samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.
  description: In cohorts 3-5:Area under the concentration-time curve in CSF until the last quantifiable concentration
  measure: SAD-CSF: Cmax
  time frame: PK samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.
  description: In cohorts 3-5:Maximum observed CSF concentration (eg C0)concentration
  measure: MAD-Plasma: AUC0-last
  time frame: PK samples will be collected after the first and fourth doses (Day 1 and Day 10) at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hours postdose.
  description: Area under the concentration-time curve until the last quantifiable concentration
  measure: MAD-Plasma: Cmax
  time frame: PK samples will be collected after the first and fourth doses (Day 1 and Day 10) at predose and at 0.16, 0.5, 1, 2, 4, 8, 12, 24, 48 and 72 hours postdose.
  description: Maximum observed plasma concentration (eg C0)
  measure: MAD-CSF:AUC0-last
  time frame: CSF collection by lumbar puncture (LP) will be performed before the first dose. At the fourth dose, on Day 10, serial CSF samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.
  description: Area under the concentration-time curve until the last quantifiable concentration
  measure: MAD-CSF: Cmax
  time frame: CSF collection by lumbar puncture (LP) will be performed before the first dose. At the fourth dose, on Day 10, serial CSF samples will be collected by lumbar catheter starting predose, and at 0.5, 2, 8, 12 and 24 hours postdose.
  description: Maximum observed CSF concentration (eg C0)
  arm group label: CS6253 Solution for Injection
  arm group type: Active Comparator
  description: SAD: Single ascending doses: CS6253 Solution for Injection dosing, 50 mg/mL, will be weight based and provided from single use 2 mL vials containing approximately 100 mg CS6253 in phosphate buffered saline (PBS) solution
  MAD: Multiple ascending doses (4x every 72 hours): CS6253 Solution for Injection dosing, 50 mg/mL, will be weight based and provided from single use 2 mL vials containing approximately 100 mg CS6253 in phosphate buffered saline (PBS) solution
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: SAD and MAD: Placebo control will be provided from vials containing physiological saline for injection in an equal amount as necessary for the active arm.
  intervention type: Drug
  intervention name: CS6253 Solution for Injection
  description: Solution for intra-venous injection, 50mg CS6253 /mL. Single-use vials containing 100 mg CS6253 (2 mL of 50 mg/mL concentration)
  arm group label: CS6253 Solution for Injection
  intervention type: Drug
  intervention name: Placebo
  description: Physiological saline solution for intra-venous injection
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Alberto M. Borobia Perez, MD, Ass.Prof
  role: Principal Investigator
  affiliation: Universidad Autónoma de Madrid, Farmacología y Terapéutica / Facultad de Medicina
  last name: Nikola Helmberg, PhD
  phone: +4366488397558
  email: nhelmberg@neuroscios.com
  last name: Barbara Fridrich
  phone: +4366488869909
  email: bfridrich@neuroscios.com
  responsible party type: Sponsor
  mesh term: Alzheimer Disease
  sharing ipd: No
  ipd description: No individual participant data will be shared