<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/NCT03276858</url>
  </required_header>
  <id_info>
    <org_study_id>CRN00808-01</org_study_id>
    <nct_id>NCT03276858</nct_id>
  </id_info>
  <brief_title>Single and Multiple-Ascending Dose Study of CRN00808 in Healthy Volunteers</brief_title>
  <official_title>A Double-Blind, Randomized, Placebo-Controlled, Single- And-Multiple-Dose Study to Evaluate the Safety, PK, and PD of CRN00808 in Healthy Volunteers and to Determine the Effect of CRN00808 on Midazolam PK</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Crinetics Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Crinetics Pharmaceuticals 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>
      This single-center study will be conducted in 3 phases: a single-ascending dose phase (up to&#xD;
      8 cohorts, 8 subjects/cohort), a multiple-dose phase (up to 5 cohorts, 9 subjects/cohort),&#xD;
      and a midazolam drug-drug interaction phase (one cohort of 8 subjects).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The single-dose phase initiates with ascending doses of an oral solution followed by a 3-way&#xD;
      crossover food effect and bioavailability (capsule formulation) cohort. Serum IGF-1 levels&#xD;
      and GHRH-analog stimulated GH levels will be assessed as pharmacodynamics measures.&#xD;
&#xD;
      The first multiple-dose (7 days dosing) cohort will be initiated after the PK and safety data&#xD;
      are available from the single-dose phase. Subsequent multiple-dose cohorts will have 10 days&#xD;
      of dosing. Serum IGF-1 level and GH levels will be assessed as pharmacodynamics measures.&#xD;
&#xD;
      The last cohort in the study is midazolam drug-drug interaction study. The dose will be&#xD;
      selected based on review of all pharmacokinetic and safety data for the single-dose and&#xD;
      multiple-dose cohorts completed. On Day 1, 8 subjects will receive a single oral 2 mg dose of&#xD;
      midazolam. Starting on Day 3 through Day 8, subjects will receive daily doses of CRN00808. On&#xD;
      Day 9, subjects will be administered CRN00808 and 2 mg midazolam together.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 22, 2017</start_date>
  <completion_date type="Actual">April 30, 2018</completion_date>
  <primary_completion_date type="Actual">April 30, 2018</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>Single and multiple-dose cohorts are placebo-controlled. The midazolam cohort does not have placebo.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blind study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 single ascending doses using clinical assessments, telemetry, and Holter monitoring and subject self-reporting</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>ECG, clinical laboratory parameters, vital signs, physical examinations, telemetry, Holter monitoring</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 multiple ascending doses using clinical assessments and subject self-reporting</measure>
    <time_frame>Day 1 through Day 21</time_frame>
    <description>ECG, clinical laboratory parameters, vital signs, physical examinations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC of CRN00808 single ascending doses</measure>
    <time_frame>Day 1 through Day 7</time_frame>
    <description>plasma AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of CRN00808 single ascending doses</measure>
    <time_frame>Day 1 through Day 7</time_frame>
    <description>plasma Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 of CRN00808 single ascending doses</measure>
    <time_frame>Day 1 through Day 7</time_frame>
    <description>plasma t1/2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of CRN00808 single ascending doses</measure>
    <time_frame>Day 1 through Day 7</time_frame>
    <description>plasma Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of CRN00808 multiple ascending doses</measure>
    <time_frame>Day 1 through Day 20</time_frame>
    <description>plasma AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of CRN00808 multiple ascending doses</measure>
    <time_frame>Day 1 through Day 20</time_frame>
    <description>plasma Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 of CRN00808 multiple ascending doses</measure>
    <time_frame>Day 1 through Day 20</time_frame>
    <description>plasma t1/2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of CRN00808 multiple ascending doses</measure>
    <time_frame>Day 1 through Day 20</time_frame>
    <description>plasma Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels</measure>
    <time_frame>Day -1 and Day 1</time_frame>
    <description>Suppression of serum GH induced by a GH secretagogue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of CRN00808 on pharmacokinetics of midazolam</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>midazolam plasma AUC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of CRN00808 on Cmax of midazolam</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>midazolam plasma Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of CRN00808 on t1/2 of midazolam</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>midazolam plasma t 1/2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of CRN00808 on Tmax of midazolam</measure>
    <time_frame>Day 1 through Day 10</time_frame>
    <description>midazolam plasma Tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative bioavailability of capsule formulation</measure>
    <time_frame>Day 1 to Day 7</time_frame>
    <description>single-dose crossover arm only</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of food on Cmax of CRN00808</measure>
    <time_frame>Day 1 to Day 7</time_frame>
    <description>plasma Cmax compared with and without food in single dose arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of food on AUC of CRN00808</measure>
    <time_frame>Day 1 to Day 7</time_frame>
    <description>Plasma AUC compared with and without food in single dose arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics of CRN00808 in multiple ascending dose cohorts assessed by serum IGF-1 and GH</measure>
    <time_frame>Day -1 to Day 21</time_frame>
    <description>serum IGF-1 and GH</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">99</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>CRN00808 Oral Solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CRN00808 oral solution, single-dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CRN00808 Oral Capsule</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CRN00808 oral capsule, single-dose and multiple-doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Oral Solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral solution, single-dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Oral Capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral capsule, single-dose and multiple doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Midazolam Oral Solution</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CRN00808</intervention_name>
    <description>Investigational drug</description>
    <arm_group_label>CRN00808 Oral Capsule</arm_group_label>
    <arm_group_label>CRN00808 Oral Solution</arm_group_label>
    <arm_group_label>Midazolam Oral Solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Solution</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo Oral Solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam oral solution</intervention_name>
    <description>Midazolam as part of the drug-drug interaction arm of the study</description>
    <arm_group_label>Midazolam Oral Solution</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo Oral Capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI 18 to 30 kg/m2&#xD;
&#xD;
          -  Females postmenopausal or surgically sterile&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any uncontrolled or active major systemic disease including, but not limited to:&#xD;
             acromegaly (with or without pituitary surgery or radiation therapy), cardiac,&#xD;
             pulmonary, gastrointestinal, metabolic, urogenital, neurological, immunological,&#xD;
             psychiatric, or neoplastic disorder with metastatic potential&#xD;
&#xD;
          -  History or presence of malignancy within the past 5 years. Subjects who have been&#xD;
             successfully treated (for 3 months or longer) with no recurrence of basal or squamous&#xD;
             cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled.&#xD;
&#xD;
          -  Use of any investigational drug within the past 60 days or 5 half-lives, whichever is&#xD;
             longer&#xD;
&#xD;
          -  Have a medically significant abnormality observed during screening or the admission&#xD;
             physical examination or in any other baseline measurements&#xD;
&#xD;
          -  Use of any prior medication without approval of the investigator within 14 days prior&#xD;
             to admission&#xD;
&#xD;
          -  Tested positive at screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis&#xD;
             C antibody (HCV-Ab) or has a history of a positive result&#xD;
&#xD;
          -  History of alcohol or substance abuse in the past 6 months&#xD;
&#xD;
          -  Any condition that in the opinion of the investigator would jeopardize the subject's&#xD;
             appropriate participation in this Phase 1 study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason Lickliter, MBBS PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nucleus Network</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nucleus Network</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>August 27, 2018</last_update_submitted>
  <last_update_submitted_qc>August 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
  </intervention_browse>
  <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/NCT03276858
org study id: CRN00808-01
nct id: NCT03276858
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This single-center study will be conducted in 3 phases: a single-ascending dose phase (up to
      8 cohorts, 8 subjects/cohort), a multiple-dose phase (up to 5 cohorts, 9 subjects/cohort),
      and a midazolam drug-drug interaction phase (one cohort of 8 subjects).
The single-dose phase initiates with ascending doses of an oral solution followed by a 3-way
      crossover food effect and bioavailability (capsule formulation) cohort. Serum IGF-1 levels
      and GHRH-analog stimulated GH levels will be assessed as pharmacodynamics measures.

      The first multiple-dose (7 days dosing) cohort will be initiated after the PK and safety data
      are available from the single-dose phase. Subsequent multiple-dose cohorts will have 10 days
      of dosing. Serum IGF-1 level and GH levels will be assessed as pharmacodynamics measures.

      The last cohort in the study is midazolam drug-drug interaction study. The dose will be
      selected based on review of all pharmacokinetic and safety data for the single-dose and
      multiple-dose cohorts completed. On Day 1, 8 subjects will receive a single oral 2 mg dose of
      midazolam. Starting on Day 3 through Day 8, subjects will receive daily doses of CRN00808. On
      Day 9, subjects will be administered CRN00808 and 2 mg midazolam together.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Single and multiple-dose cohorts are placebo-controlled. The midazolam cohort does not have placebo.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blind study
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 single ascending doses using clinical assessments, telemetry, and Holter monitoring and subject self-reporting
time frame: Day 1 through Day 10
description: ECG, clinical laboratory parameters, vital signs, physical examinations, telemetry, Holter monitoring
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of CRN00808 multiple ascending doses using clinical assessments and subject self-reporting
time frame: Day 1 through Day 21
description: ECG, clinical laboratory parameters, vital signs, physical examinations
measure: AUC of CRN00808 single ascending doses
time frame: Day 1 through Day 7
description: plasma AUC
measure: Cmax of CRN00808 single ascending doses
time frame: Day 1 through Day 7
description: plasma Cmax
measure: t1/2 of CRN00808 single ascending doses
time frame: Day 1 through Day 7
description: plasma t1/2
measure: Tmax of CRN00808 single ascending doses
time frame: Day 1 through Day 7
description: plasma Tmax
measure: AUC of CRN00808 multiple ascending doses
time frame: Day 1 through Day 20
description: plasma AUC
measure: Cmax of CRN00808 multiple ascending doses
time frame: Day 1 through Day 20
description: plasma Cmax
measure: t1/2 of CRN00808 multiple ascending doses
time frame: Day 1 through Day 20
description: plasma t1/2
measure: Tmax of CRN00808 multiple ascending doses
time frame: Day 1 through Day 20
description: plasma Tmax
measure: Pharmacodynamics of CRN00808 in single ascending dose cohorts assessed by GHRH analog stimulated GH levels
time frame: Day -1 and Day 1
description: Suppression of serum GH induced by a GH secretagogue
measure: Effect of CRN00808 on pharmacokinetics of midazolam
time frame: Day 1 through Day 10
description: midazolam plasma AUC
measure: Effect of CRN00808 on Cmax of midazolam
time frame: Day 1 through Day 10
description: midazolam plasma Cmax
measure: Effect of CRN00808 on t1/2 of midazolam
time frame: Day 1 through Day 10
description: midazolam plasma t 1/2
measure: Effect of CRN00808 on Tmax of midazolam
time frame: Day 1 through Day 10
description: midazolam plasma Tmax
measure: Relative bioavailability of capsule formulation
time frame: Day 1 to Day 7
description: single-dose crossover arm only
measure: Effect of food on Cmax of CRN00808
time frame: Day 1 to Day 7
description: plasma Cmax compared with and without food in single dose arm
measure: Effect of food on AUC of CRN00808
time frame: Day 1 to Day 7
description: Plasma AUC compared with and without food in single dose arm
measure: Pharmacodynamics of CRN00808 in multiple ascending dose cohorts assessed by serum IGF-1 and GH
time frame: Day -1 to Day 21
description: serum IGF-1 and GH
arm group label: CRN00808 Oral Solution
arm group type: Experimental
description: CRN00808 oral solution, single-dose
arm group label: CRN00808 Oral Capsule
arm group type: Experimental
description: CRN00808 oral capsule, single-dose and multiple-doses
arm group label: Placebo Oral Solution
arm group type: Placebo Comparator
description: Placebo oral solution, single-dose
arm group label: Placebo Oral Capsule
arm group type: Placebo Comparator
description: Placebo oral capsule, single-dose and multiple doses
arm group label: Midazolam Oral Solution
arm group type: Other
description: Midazolam oral solution, two single-doses as part of the drug-drug interaction arm of the study
intervention type: Drug
intervention name: CRN00808
description: Investigational drug
arm group label: CRN00808 Oral Capsule
arm group label: CRN00808 Oral Solution
arm group label: Midazolam Oral Solution
intervention type: Drug
intervention name: Placebo Oral Solution
description: Placebo
arm group label: Placebo Oral Solution
intervention type: Drug
intervention name: Midazolam oral solution
description: Midazolam as part of the drug-drug interaction arm of the study
arm group label: Midazolam Oral Solution
intervention type: Drug
intervention name: Placebo oral capsule
description: Placebo
arm group label: Placebo Oral Capsule
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jason Lickliter, MBBS PhD
role: Principal Investigator
affiliation: Nucleus Network
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Midazolam
mesh term: Pharmaceutical Solutions
sharing ipd: No