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/NCT06030375</url>
    </required_header>
    <id_info>
      <org_study_id>KAN0004</org_study_id>
      <secondary_id>2019-004585-18</secondary_id>
      <nct_id>NCT06030375</nct_id>
    </id_info>
    <brief_title>Safety, Tolerability and Pharmacokinetics After Continuous Infusion of KAND567</brief_title>
    <official_title>Safety, Tolerability and Pharmacokinetics After Continuous Infusion of KAND567. A Single-centre, Placebo-controlled, Randomised, Double-blind Study in Healthy Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Kancera AB</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Kancera AB</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 study was planned to consist of 24 healthy subjects in 3 dosing cohorts receiving a&#xD;
        continuous i.v. infusion of KAND567 or placebo for 6 h (6 subjects on active and 2 subjects&#xD;
        on placebo per cohort), with the option of two additional cohorts of the same size and group&#xD;
        composition.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The 3 planned dose levels of KAND567 were based on preliminary data from previous i.v.&#xD;
        infusions and were chosen to obtain approximate Css levels of 0.5, 1.0 and 2.0 μM. The dose&#xD;
        levels were 33.8 mg/6 h (cohort 1), 67 mg/6 h (cohort 2), or 134 mg/6 h (cohort 3).&#xD;
  &#xD;
        Each cohort of participants was planned to consist of 8 subjects (2 on placebo and 6 on&#xD;
        active drug), i.e. a total of 24 subjects. A sentinel approach was used for all three&#xD;
        cohorts, starting dosing with two subjects (one on active drug, one on placebo). If safe and&#xD;
        tolerable, an additional two or three subjects will be administered. If safe and tolerable,&#xD;
        the remaining three or four subjects of the cohort were dosed. There was an evaluation of&#xD;
        safety and tolerability from the previous cohort prior to proceeding to the next cohort.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">February 17, 2020</start_date>
    <completion_date type="Actual">April 27, 2020</completion_date>
    <primary_completion_date type="Actual">April 27, 2020</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>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>The physical appearance of the KAND567 solution is a clear transparent solution with a distinct smell. An unblinded pharmacist or registered nurse at the study centre therefore prepared the dosing solutions.&#xD;
  There were two unblinded persons working together, one person handled the IMP and perform the dispensing according to the randomisation list and the other person monitored the process.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Safety and tolerability after continuous infusion of KAND567, as measured by adverse events (AEs)</measure>
      <time_frame>From the first IMP administration (Day 1) until the last follow-up visit (Day 30)</time_frame>
      <description>Measured by the occurrence of AEs and serious adverse events (SAEs)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety and tolerability after continuous infusion of KAND567, as measured by vital signs</measure>
      <time_frame>From the first IMP administration (Day 1) until the last follow-up visit (Day 30)</time_frame>
      <description>Measured by the occurrence of clinically abnormal vital signs</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety and tolerability after continuous infusion of KAND567, as measured by ECG</measure>
      <time_frame>From the first IMP administration (Day 1) until the last follow-up visit (Day 30)</time_frame>
      <description>Measured by the occurrence of clinically abnormal electrocardiography (ECG)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Safety and tolerability after continuous infusion of KAND567, as measured by lab safety tests</measure>
      <time_frame>From the first IMP administration (Day 1) until the last follow-up visit (Day 30)</time_frame>
      <description>Measured by the occurrence of clinically abnormal lab test results (routine clinical chemistry, haematology, and urinalysis)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by Css</measure>
      <time_frame>From the first IMP administration (Day 1) until Day 2</time_frame>
      <description>Measured by plasma drug concentration at steady state (Css)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by AUC</measure>
      <time_frame>From the first IMP administration (Day 1) until Day 2</time_frame>
      <description>Measured by the area under the plasma concentration-time curve (AUC)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by t1/2z</measure>
      <time_frame>From the first IMP administration (Day 1) until Day 2</time_frame>
      <description>Measured by terminal half-life (t1/2z)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by Vss</measure>
      <time_frame>From the first IMP administration (Day 1) until Day 2</time_frame>
      <description>Measured by the apparent volume of distribution at steady state (Vss)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by CL</measure>
      <time_frame>From the first IMP administration (Day 1) until Day 2</time_frame>
      <description>Measured by the systemic clearance (CL)</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">23</enrollment>
    <condition>Healthy</condition>
    <arm_group>
      <arm_group_label>KAND567 in ascending doses</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>In each of the 3 cohorts, 6 subjects were planned to be randomised to receive KAND567. The dose levels were 33.8 mg/6 h (cohort 1), 67 mg/6 h (cohort 2), or 134 mg/6 h (cohort 3).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>In each of the 3 cohorts, 2 subjects were planned to be randomised to receive Placebo.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>KAND567</intervention_name>
      <description>Continuous intravenous infusion for 6 hours</description>
      <arm_group_label>KAND567 in ascending doses</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Continuous intravenous infusion for 6 hours</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Provision of written informed consent prior to any study specific procedures&#xD;
  &#xD;
            -  Body weight &gt; 50 kg&#xD;
  &#xD;
            -  Body Mass Index (BMI) ≥ 19 and ≤ 30 kg/m^2 at screening&#xD;
  &#xD;
            -  Healthy male and female subjects aged ≥ 18 and ≤ 65 years at screening&#xD;
  &#xD;
            -  Male subjects must agree to use an adequate method of contraception. Male subjects who&#xD;
               are heterosexually active must use, with their partner, a condom AND one of the&#xD;
               following methods of highly effective contraception from the time of IMP&#xD;
               administration until 90 days after dosing of IMP.&#xD;
  &#xD;
                 -  oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable or&#xD;
                    implanted hormonal contraceptives&#xD;
  &#xD;
                 -  intrauterine device&#xD;
  &#xD;
                 -  intrauterine system (for example progestin-releasing coil)&#xD;
  &#xD;
                 -  vasectomized male (with appropriate post vasectomy documentation of the absence&#xD;
                    of sperm in the ejaculate)&#xD;
  &#xD;
                 -  bilateral tubal occlusion or hysterectomy&#xD;
  &#xD;
            -  Female subject must be of non-childbearing potential (defined as pre-menopausal&#xD;
               females with a documented tubal ligation or hysterectomy or bilateral oophorectomy; or&#xD;
               as post-menopausal females defined as 12 months' amenorrhoea [in questionable cases a&#xD;
               blood sample with simultaneous follicle stimulating hormone 25-140 IE/L and estradiol&#xD;
               &lt; 200 pmol/L is confirmatory])&#xD;
  &#xD;
            -  Willingness and ability to comply with study procedures, visit schedules, study&#xD;
               restrictions and requirements&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Present or known history of clinically significant cardio- or cerebrovascular,&#xD;
               pulmonary, renal, hepatic, neurological, mental, metabolic, endocrine, haematological,&#xD;
               gastrointestinal disorder, significant respiratory disease, sleep apnoea, narcolepsy&#xD;
               or any other major disorder that may interfere with the objectives of the study, as&#xD;
               judged by the investigator&#xD;
  &#xD;
            -  Any clinically significant abnormalities in physical examination, electrocardiogram&#xD;
               (ECG; e.g. QTcF&gt;450 ms), clinical chemistry, haematology or urinalysis results at&#xD;
               screening, as judged by the investigator&#xD;
  &#xD;
            -  Clinically significant abnormal blood pressure (treated or untreated), defined as&#xD;
               systolic pressure above or equal to 160 mmHg and/or diastolic blood pressure above or&#xD;
               equal to 90 mmHg at screening&#xD;
  &#xD;
            -  Pulse rate &lt; 45 bpm at screening&#xD;
  &#xD;
            -  Clinically significant illness within the 5 days prior to the administration of the&#xD;
               IMP&#xD;
  &#xD;
            -  Any positive result on screening for serum hepatitis B surface antigen, hepatitis C&#xD;
               antibody or human immunodeficiency virus (HIV)&#xD;
  &#xD;
            -  Known or suspected drug or alcohol abuse or positive screen for drugs of abuse test or&#xD;
               positive alcohol breath test at screening visit or any time prior to randomisation&#xD;
  &#xD;
            -  Smoking &gt; 5 cigarettes per day, or inability to refrain from smoking or using other&#xD;
               nicotine-containing products during the stay at the study centre.&#xD;
  &#xD;
            -  Subject who has received any investigational drug within the last 3 months before&#xD;
               administration of IMP&#xD;
  &#xD;
            -  Plasma donation within one month of screening visit, or any blood donation/ blood loss&#xD;
               &gt; 450 mL during the 3 months prior to screening visit&#xD;
  &#xD;
            -  Use of the herbal remedy St. John's Wort within two weeks prior to the first dose of&#xD;
               the IMP (induces cytochrome P450-3A4)&#xD;
  &#xD;
            -  Use of prescribed medication during the two weeks prior to the administration of the&#xD;
               IMP (or longer if the prescribed medication has a half-life long enough to potentially&#xD;
               expose the subject to any significant systemic exposure, as judged by the&#xD;
               investigator)&#xD;
  &#xD;
            -  Use of over-the-counter drugs (including herbals (St. John's Wort - see above),&#xD;
               vitamins and minerals) during one week prior to the administration of the IMP or need&#xD;
               for concomitant medication during the study. However, occasional paracetamol for pain&#xD;
               relief is allowed (up to 3 g per 24 hours)&#xD;
  &#xD;
            -  Female subjects: Positive pregnancy test at screening visit or at any time prior to&#xD;
               randomisation&#xD;
  &#xD;
            -  Investigator considers the subject unlikely to comply with study procedures,&#xD;
               restrictions and requirements&#xD;
  &#xD;
            -  Subject has an eGFR &lt; 80 mL/min/1.73m^2 at screening.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Mika Scheinin, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Clinical Research Services Turku (CRST)</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Clinical Research Services Turku (CRST)</name>
        <address>
          <city>Turku</city>
          <zip>20520</zip>
          <country>Finland</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Finland</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 24, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</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>
  
  
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/NCT06030375
  org study id: KAN0004
  secondary id: 2019-004585-18
  nct id: NCT06030375
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The study was planned to consist of 24 healthy subjects in 3 dosing cohorts receiving a
        continuous i.v. infusion of KAND567 or placebo for 6 h (6 subjects on active and 2 subjects
        on placebo per cohort), with the option of two additional cohorts of the same size and group
        composition.
  The 3 planned dose levels of KAND567 were based on preliminary data from previous i.v.
        infusions and were chosen to obtain approximate Css levels of 0.5, 1.0 and 2.0 μM. The dose
        levels were 33.8 mg/6 h (cohort 1), 67 mg/6 h (cohort 2), or 134 mg/6 h (cohort 3).
  
        Each cohort of participants was planned to consist of 8 subjects (2 on placebo and 6 on
        active drug), i.e. a total of 24 subjects. A sentinel approach was used for all three
        cohorts, starting dosing with two subjects (one on active drug, one on placebo). If safe and
        tolerable, an additional two or three subjects will be administered. If safe and tolerable,
        the remaining three or four subjects of the cohort were dosed. There was an evaluation of
        safety and tolerability from the previous cohort prior to proceeding to the next cohort.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: The physical appearance of the KAND567 solution is a clear transparent solution with a distinct smell. An unblinded pharmacist or registered nurse at the study centre therefore prepared the dosing solutions.
  There were two unblinded persons working together, one person handled the IMP and perform the dispensing according to the randomisation list and the other person monitored the process.
  measure: Safety and tolerability after continuous infusion of KAND567, as measured by adverse events (AEs)
  time frame: From the first IMP administration (Day 1) until the last follow-up visit (Day 30)
  description: Measured by the occurrence of AEs and serious adverse events (SAEs)
  measure: Safety and tolerability after continuous infusion of KAND567, as measured by vital signs
  time frame: From the first IMP administration (Day 1) until the last follow-up visit (Day 30)
  description: Measured by the occurrence of clinically abnormal vital signs
  measure: Safety and tolerability after continuous infusion of KAND567, as measured by ECG
  time frame: From the first IMP administration (Day 1) until the last follow-up visit (Day 30)
  description: Measured by the occurrence of clinically abnormal electrocardiography (ECG)
  measure: Safety and tolerability after continuous infusion of KAND567, as measured by lab safety tests
  time frame: From the first IMP administration (Day 1) until the last follow-up visit (Day 30)
  description: Measured by the occurrence of clinically abnormal lab test results (routine clinical chemistry, haematology, and urinalysis)
  measure: Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by Css
  time frame: From the first IMP administration (Day 1) until Day 2
  description: Measured by plasma drug concentration at steady state (Css)
  measure: Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by AUC
  time frame: From the first IMP administration (Day 1) until Day 2
  description: Measured by the area under the plasma concentration-time curve (AUC)
  measure: Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by t1/2z
  time frame: From the first IMP administration (Day 1) until Day 2
  description: Measured by terminal half-life (t1/2z)
  measure: Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by Vss
  time frame: From the first IMP administration (Day 1) until Day 2
  description: Measured by the apparent volume of distribution at steady state (Vss)
  measure: Pharmacokinetics (PK) after continuous infusion of KAND567, as measured by CL
  time frame: From the first IMP administration (Day 1) until Day 2
  description: Measured by the systemic clearance (CL)
  arm group label: KAND567 in ascending doses
  arm group type: Active Comparator
  description: In each of the 3 cohorts, 6 subjects were planned to be randomised to receive KAND567. The dose levels were 33.8 mg/6 h (cohort 1), 67 mg/6 h (cohort 2), or 134 mg/6 h (cohort 3).
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: In each of the 3 cohorts, 2 subjects were planned to be randomised to receive Placebo.
  intervention type: Drug
  intervention name: KAND567
  description: Continuous intravenous infusion for 6 hours
  arm group label: KAND567 in ascending doses
  intervention type: Other
  intervention name: Placebo
  description: Continuous intravenous infusion for 6 hours
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Mika Scheinin, MD, PhD
  role: Principal Investigator
  affiliation: Clinical Research Services Turku (CRST)
  facility: 
  country: Finland
  responsible party type: Sponsor
  sharing ipd: No