<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/NCT04489797</url>
  </required_header>
  <id_info>
    <org_study_id>D822FC00008</org_study_id>
    <nct_id>NCT04489797</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Effects of Proton-pump Inhibitor on Acalabrutinib Capsule When Administered Orally With COCA-COLA in Healthy Participants</brief_title>
  <official_title>A Phase I, Open-label, Randomized, Single-dose Study of Acalabrutinib in Healthy Subjects to Evaluate the Effect of Proton-pump Inhibitor (Rabeprazole) on Acalabrutinib Capsule When Administered Orally With COCA-COLA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Acerta Pharma BV</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</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 study is being conducted to support the clinical development of acalabrutinib in&#xD;
      participants who need treatment with proton pump inhibitors while taking acalabrutinib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single-center, randomized study in healthy participants to evaluate&#xD;
      the effect of proton-pump inhibitors (rabeprazole; PPI) on acalabrutinib 100-mg capsule dosed&#xD;
      orally with COCA-COLA. Participants will receive a single dose of acalabrutinib alone or with&#xD;
      rabeprazole, and pharmacokinetic (PK), safety and tolerability will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Actual">August 28, 2020</completion_date>
  <primary_completion_date type="Actual">August 28, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>This is open-label, randomized, single-dose study. The participants will be divided in 2 treatment arms as follows:&#xD;
Arm A (only acalabrutinib)&#xD;
Arm B (acalabrutinib + rabeprazole)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under plasma concentration-time curve from time zero to infinity (AUCinf)</measure>
    <time_frame>Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2</time_frame>
    <description>Assessment of AUCinf for acalabrutinib and ACP-5862 (metabolite of acalabrutinib) following administration of capsule with and without rabeprazole.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)</measure>
    <time_frame>Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2</time_frame>
    <description>Assessment of AUClast for acalabrutinib and ACP-5862 following administration of capsule with and without rabeprazole.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2</time_frame>
    <description>Assessment of Cmax for acalabrutinib and ACP-5862 following administration of capsule with and without rabeprazole.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events and serious adverse events</measure>
    <time_frame>From screening until Follow-up visit (Upto 5 to 6 Weeks)</time_frame>
    <description>Assessment of the safety and tolerability of acalabrutinib capsule when administered with COCA-COLA and rabeprazole.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Infectious Disease</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive single oral dose of acalabrutinib capsule with 100 mL of water.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive single oral dose of acalabrutinib capsule taken with 100 mL of COCA-COLA along with 20 mg rabeprazole.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acalabrutinib</intervention_name>
    <description>Participants will receive single oral dose of acalabrutinib on day 1 as per the arms they are randomized.</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rabeprazole</intervention_name>
    <description>Participants will receive twice daily oral dose of 20 mg rabeprazole on days -3, -2, and -1.</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Capable of giving signed informed consent.&#xD;
&#xD;
          -  Male participants and their female partners/spouses must adhere to the contraception&#xD;
             methods.&#xD;
&#xD;
          -  Female participants must have a negative pregnancy test at screening, must not be&#xD;
             lactating, and must be of non-childbearing potential, confirmed at screening by&#xD;
             fulfilling one of the following criteria:&#xD;
&#xD;
               -  Postmenopausal defined as amenorrhea for at least 12 months following cessation&#xD;
                  of all exogenous hormonal treatments and follicle stimulating hormone levels in&#xD;
                  the postmenopausal range.&#xD;
&#xD;
               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral&#xD;
                  oophorectomy, or bilateral salpingectomy but not bilateral tubal ligation.&#xD;
&#xD;
          -  Have a body mass index between 18.5 and 30 kg/m^2, inclusive, and weigh at least 50 kg&#xD;
             and no more than 100 kg, inclusive, at screening.&#xD;
&#xD;
          -  Understands the study procedures in the informed consent form and willing and able to&#xD;
             comply with the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History or presence of any clinically significant disease (including active&#xD;
             coronavirus disease 2019 infection).&#xD;
&#xD;
          -  History or presence of gastrointestinal, hepatic or renal disease, or any other&#xD;
             condition known to interfere with absorption, distribution, metabolism, or excretion&#xD;
             of drugs.&#xD;
&#xD;
          -  Any clinically significant illness, medical/surgical procedure, or trauma within 30&#xD;
             days of the first administration of investigational medicinal product (IMP).&#xD;
&#xD;
          -  Any clinically significant abnormalities in hematology, coagulation, clinical&#xD;
             chemistry, or urinalysis results, at screening defined as:&#xD;
&#xD;
               -  Hemoglobin less than lower limit of normal.&#xD;
&#xD;
               -  Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase&#xD;
                  or serum bilirubin (total and direct) &gt; 1.5 upper limit of normal.&#xD;
&#xD;
          -  Any clinically significant abnormal findings in vital signs at screening (eg, systolic&#xD;
             blood pressure [BP] &lt; 90 mmHg or ≥ 140 mmHg; diastolic BP &lt; 50 mmHg or ≥ 90 mmHg;&#xD;
             pulse &lt; 50 or &gt; 90 bpm).&#xD;
&#xD;
          -  Any clinically significant abnormalities on standard 12-lead electrocardiogram at&#xD;
             screening.&#xD;
&#xD;
          -  Any positive result on screening for serum Hepatitis B surface antigen, hepatitis B,&#xD;
             hepatitis C, and Human immunodeficiency virus antibody.&#xD;
&#xD;
          -  Has received a new chemical entity within 90 days of the first administration of IMP&#xD;
             in this study. The period of exclusion begins 90 days after the final dose or 30 days&#xD;
             after the last visit whichever is the longest.&#xD;
&#xD;
          -  Plasma donation within 30 days of screening or any blood donation/loss more than 500&#xD;
             mL during the 90 days prior to screening.&#xD;
&#xD;
          -  History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or&#xD;
             history of hypersensitivity to drugs with a similar chemical structure or class to&#xD;
             acalabrutinib or rabeprazole.&#xD;
&#xD;
          -  Current smokers or those who have smoked or used nicotine products within the 90 days&#xD;
             prior to screening.&#xD;
&#xD;
          -  Positive screen for drugs of abuse or cotinine at screening.&#xD;
&#xD;
          -  Treatment with a strong cytochrome P450 3A (CYP3A) inhibitor (within 14 days before&#xD;
             first administration of IMP) or strong CYP3A inducer (within 28 days before first&#xD;
             administration of IMP).&#xD;
&#xD;
          -  Use of any prescribed or non-prescribed medication including antacids, analgesics&#xD;
             (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of&#xD;
             20 to 600 times the recommended daily dose) and minerals during the 14 days prior to&#xD;
             the first administration of IMP or longer if the medication has a long half-life.&#xD;
             Hormonal replacement therapy will not be allowed.&#xD;
&#xD;
          -  Known or suspected history of alcohol or drug abuse, or excessive intake of alcohol.&#xD;
&#xD;
          -  Excessive intake of caffeine-containing drinks or food or would likely be unable to&#xD;
             refrain from the use of caffeine-containing beverages during in-house stay at the&#xD;
             Clinical Unit.&#xD;
&#xD;
          -  Involvement of any AstraZeneca, Acerta Pharma, Parexel or study site employee or their&#xD;
             close relatives.&#xD;
&#xD;
          -  Judgment by the Investigator that the participant should not participate in the study&#xD;
             if they have any ongoing or recent (ie, during the screening period) minor medical&#xD;
             complaints that may interfere with the interpretation of study data or are considered&#xD;
             unlikely to comply with study procedures, restrictions, and requirements.&#xD;
&#xD;
          -  Participants who cannot communicate reliably with the Investigator.&#xD;
&#xD;
          -  Vulnerable participants, eg, kept in detention, protected adults under guardianship,&#xD;
             trusteeship, or committed to an institution by governmental or juridical order.&#xD;
&#xD;
          -  Inability to swallow acalabrutinib capsules.&#xD;
&#xD;
          -  Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper&#xD;
             respiratory tract infections). Note: Participants with localized cutaneous fungal&#xD;
             infections are eligible.&#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>Peter J. Winkle, MD FACP FACG CPI</last_name>
    <role>Principal Investigator</role>
    <affiliation>Anaheim Clinical Trials</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>October 29, 2020</last_update_submitted>
  <last_update_submitted_qc>October 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Bioavailability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acalabrutinib</mesh_term>
    <mesh_term>Rabeprazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:&#xD;
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_description>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </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/NCT04489797
org study id: D822FC00008
nct id: NCT04489797
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is being conducted to support the clinical development of acalabrutinib in
      participants who need treatment with proton pump inhibitors while taking acalabrutinib.
This is an open-label, single-center, randomized study in healthy participants to evaluate
      the effect of proton-pump inhibitors (rabeprazole; PPI) on acalabrutinib 100-mg capsule dosed
      orally with COCA-COLA. Participants will receive a single dose of acalabrutinib alone or with
      rabeprazole, and pharmacokinetic (PK), safety and tolerability will be assessed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is open-label, randomized, single-dose study. The participants will be divided in 2 treatment arms as follows:
Arm A (only acalabrutinib)
Arm B (acalabrutinib + rabeprazole)
primary purpose: Treatment
masking: None (Open Label)
measure: Area under plasma concentration-time curve from time zero to infinity (AUCinf)
time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2
description: Assessment of AUCinf for acalabrutinib and ACP-5862 (metabolite of acalabrutinib) following administration of capsule with and without rabeprazole.
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2
description: Assessment of AUClast for acalabrutinib and ACP-5862 following administration of capsule with and without rabeprazole.
measure: Maximum observed plasma concentration (Cmax)
time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose on Day 1, and 24 hours post-dose on Day 2
description: Assessment of Cmax for acalabrutinib and ACP-5862 following administration of capsule with and without rabeprazole.
measure: Number of participants with adverse events and serious adverse events
time frame: From screening until Follow-up visit (Upto 5 to 6 Weeks)
description: Assessment of the safety and tolerability of acalabrutinib capsule when administered with COCA-COLA and rabeprazole.
arm group label: Arm A
arm group type: Experimental
description: Participants will receive single oral dose of acalabrutinib capsule with 100 mL of water.
arm group label: Arm B
arm group type: Experimental
description: Participants will receive single oral dose of acalabrutinib capsule taken with 100 mL of COCA-COLA along with 20 mg rabeprazole.
intervention type: Drug
intervention name: Acalabrutinib
description: Participants will receive single oral dose of acalabrutinib on day 1 as per the arms they are randomized.
arm group label: Arm A
arm group label: Arm B
intervention type: Drug
intervention name: Rabeprazole
description: Participants will receive twice daily oral dose of 20 mg rabeprazole on days -3, -2, and -1.
arm group label: Arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Peter J. Winkle, MD FACP FACG CPI
role: Principal Investigator
affiliation: Anaheim Clinical Trials
facility: 
country: United States
responsible party type: Sponsor
mesh term: Communicable Diseases
mesh term: Infections
mesh term: Acalabrutinib
mesh term: Rabeprazole
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home