<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/NCT03032536</url>
  </required_header>
  <id_info>
    <org_study_id>AL-3778-1002</org_study_id>
    <secondary_id>U1111-1187-4391</secondary_id>
    <nct_id>NCT03032536</nct_id>
  </id_info>
  <brief_title>Study of the Relative Oral Bioavailability of AL-3778 Tablets and Drug Interaction With Entecavir or Tenofovir Disoproxil Fumarate in Healthy Volunteers</brief_title>
  <official_title>A Randomized, Open-label, Multi-part Study of the Relative Oral Bioavailability of AL-3778 Tablets and Drug Interaction With Entecavir or Tenofovir Disoproxil Fumarate in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alios Biopharma Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alios Biopharma Inc.</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 is an open-label, randomized, multi-part study to evaluate the relative oral&#xD;
      bioavailability of a tablet formulation of AL-3778 (formerly NVR 3-778) administered under&#xD;
      fasted and fed conditions (Parts 1 and 2) and the drug-drug interaction between AL-3778 and&#xD;
      entecavir or tenofovir disoproxil fumarate (Part 3).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision.&#xD;
  </why_stopped>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Actual">June 28, 2017</completion_date>
  <primary_completion_date type="Actual">June 28, 2017</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Maximum observed plasma concentration (Cmax)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUC∞)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 1 (Cmax. Day 1)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 1 (Cmin, Day 1)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval on Day 1 (AUC0-Τ, Day 1)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Minimum observed plasma concentration (C_min)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Predose plasma concentrations (C_0-h)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Last observed plasma concentration (C_last)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Time of the maximum observed plasma concentration (T_max)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Time to last measurable plasma concentration (T_last)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Apparent oral clearance (CL/F)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Apparent volume of distribution (Vz/F)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Apparent terminal half-life (t½)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 14 (Cmax. Day 14)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 14 (Cmin, Day 14)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval, tau, on Day 14 (AUC0-Τ, Day 14)</measure>
    <time_frame>At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence, nature, and severity of adverse events</measure>
    <time_frame>Screening to Day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Vital Signs during and after study drug administration</measure>
    <time_frame>Day 1 to Day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in physical examinations during and after study drug administration</measure>
    <time_frame>Day 1 to Day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in clinical laboratory results during and after study drug administration</measure>
    <time_frame>Day 1 to Day 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in electrocardiogram results during and after study drug administration</measure>
    <time_frame>Day 1 to Day 22</time_frame>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Hepatitis B</condition>
  <condition>Chronic Hepatitis B</condition>
  <condition>Viral Hepatitis B</condition>
  <arm_group>
    <arm_group_label>Treatments A, B, C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 1: Cross-Over&#xD;
Treatment A: AL-3778 6 x 100-mg capsules (fasted) once.&#xD;
Treatment B: AL-3778 2 x 300-mg tablets (fasted) once&#xD;
Treatment C: AL-3778 2 x 300-mg tablets (high-fat meal) once.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatments D, E, F</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 2 (optional): Cross-Over&#xD;
Treatment D: AL-3778 2×300-mg tablets (fasted) once.&#xD;
Treatment E: AL-3778 tablet Dose (fasted) once. Dose will match Treatment F dose and will be:&#xD;
1000mg: 2 x 500-mg OR&#xD;
800mg: 1 x 300-mg + 1 x 500-mg OR&#xD;
700mg: 1 x 200-mg + 1 x 500-mg&#xD;
Treatment F: AL-3778 tablet Dose (high-fat meal) once. Dose will match Treatment E dose and will be:&#xD;
1000mg: 2 x 500-mg OR&#xD;
800mg: 1 x 300-mg + 1 x 500-mg OR&#xD;
700mg: 1 x 200-mg + 1 x 500-mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment G</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 3: AL-3778 twice daily administered under fasted conditions for 14 days.&#xD;
Dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:&#xD;
600mg: 2 x 300-mg OR&#xD;
1000mg: 2 x 500-mg OR&#xD;
800mg: 1 x 300-mg + 1 x 500-mg OR&#xD;
700mg: 1 x 200-mg + 1 x 500-mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment H</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Part 3: Entecavir 0.5 mg once daily administered under fasted conditions for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment I</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 3: AL-3778 twice daily with entecavir 0.5 mg once daily both administered under fasted conditions for 14 days.&#xD;
AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:&#xD;
600mg: 2 x 300-mg OR&#xD;
1000mg: 2 x 500-mg OR&#xD;
800mg: 1 x 300-mg + 1 x 500-mg OR&#xD;
700mg: 1 x 200-mg + 1 x 500-mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment J</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Part 3: Tenofovir disoproxil fumarate 300 mg once daily administered under fasted conditions for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment K</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part 3: AL-3778 twice daily and tenofovir disoproxil fumarate 300 mg once daily both administered under fasted conditions for 14 days.&#xD;
AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:&#xD;
600mg: 2 x 300-mg OR&#xD;
1000mg: 2 x 500-mg OR&#xD;
800mg: 1 x 300-mg + 1 x 500-mg OR&#xD;
700mg: 1 x 200-mg + 1 x 500-mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AL-3778</intervention_name>
    <description>AL-3778 tablets or capsules</description>
    <arm_group_label>Treatment G</arm_group_label>
    <arm_group_label>Treatment I</arm_group_label>
    <arm_group_label>Treatment K</arm_group_label>
    <arm_group_label>Treatments A, B, C</arm_group_label>
    <arm_group_label>Treatments D, E, F</arm_group_label>
    <other_name>NVR 3-778, JNJ-63595948, ALS-003778</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entecavir</intervention_name>
    <description>Entecavir once daily for 14 days</description>
    <arm_group_label>Treatment H</arm_group_label>
    <arm_group_label>Treatment I</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir disoproxil fumarate</intervention_name>
    <description>Tenofovir disoproxil fumarate once daily for 14 days</description>
    <arm_group_label>Treatment J</arm_group_label>
    <arm_group_label>Treatment K</arm_group_label>
    <other_name>Viread</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria for All Subjects:&#xD;
&#xD;
          1. Subject has provided written consent.&#xD;
&#xD;
          2. In the investigator's opinion, the subject is able to understand and comply with&#xD;
             protocol requirements, instructions, and study restrictions and is likely to complete&#xD;
             the study as planned.&#xD;
&#xD;
          3. Subject is in good health as deemed by the investigator, based on the totality of&#xD;
             findings following a medical evaluation, including medical history, physical&#xD;
             examination, laboratory tests and ECG.&#xD;
&#xD;
          4. Male or female, 18-60 years of age.&#xD;
&#xD;
          5. Body mass index 18-30 kg/m2, inclusive. The minimum weight is 50 kg.&#xD;
&#xD;
          6. A female subject is eligible to participate in this study if she is of&#xD;
             non-childbearing potential (defined as females with a documented tubal ligation,&#xD;
             bilateral oophorectomy or hysterectomy) or postmenopausal (defined as 12 months of&#xD;
             spontaneous amenorrhea and follicle stimulating hormone level within the laboratory's&#xD;
             reference range for postmenopausal females). A post-menopausal female receiving&#xD;
             hormone replacement therapy who is willing to discontinue hormone therapy 28 days&#xD;
             before study drug dosing and agrees to remain off hormone replacement therapy for the&#xD;
             duration of the study may be eligible for study participation.&#xD;
&#xD;
          7. If male, subject is surgically sterile or practicing required forms of birth control&#xD;
             until 6 months after the last dose of the study drug(s). Males must agree to refrain&#xD;
             from sperm donation from check-in through 6 months after the last dose of the study&#xD;
             drug(s).&#xD;
&#xD;
          8. Subject has been a nonsmoker and has not used nicotine or nicotine-containing products&#xD;
             for at least 6 months.&#xD;
&#xD;
          9. Subjects who participated in Part 1 and/or Part 2 may participate in subsequent&#xD;
             Part(s) upon satisfactory completion of a posttreatment visit, 7 days (+2 days)&#xD;
             following the subject's last dose, and provided they continue to meet all of the&#xD;
             inclusion criteria and none of the exclusion criteria.&#xD;
&#xD;
        Main exclusion criteria:&#xD;
&#xD;
          1. Subject is mentally or legally incapacitated, has significant emotional problems at&#xD;
             the time of prestudy (screening) visit or expected during the conduct of the study or&#xD;
             has a history of a clinically significant psychiatric disorder over the last 5 to 10&#xD;
             years.&#xD;
&#xD;
          2. Subject has a history of any illness that, in the opinion of the investigator, would&#xD;
             confound the objectives or results of the study or poses an additional risk to the&#xD;
             subject by their participation in the study.&#xD;
&#xD;
          3. Subject has an estimated creatinine clearance of ≤80 mL/min based on the&#xD;
             Cockcroft-Gault equation; An actual creatinine clearance, as determined by a 24-hour&#xD;
             urine collection, may be used in place of, or in conjunction with, the Cockcroft-Gault&#xD;
             equation; subjects who have an actual or estimated creatinine clearance within 10% of&#xD;
             80 mL/min may be enrolled in the study at the discretion of the investigator.&#xD;
&#xD;
          4. Pregnant or nursing (lactating) females, confirmed by a positive human chorionic&#xD;
             gonadotropin laboratory test or females contemplating pregnancy. Men whose female&#xD;
             partners are pregnant or contemplating pregnancy from the date of screening until 6&#xD;
             months after their last dose of study drugs.&#xD;
&#xD;
          5. Clinically significant cardiovascular, respiratory, skeletal, renal, gastrointestinal,&#xD;
             hematologic, hepatic, immunological, neurologic, endocrine, genitourinary&#xD;
             abnormalities or disease or any other medical illness as determined by the&#xD;
             investigator or Sponsor's Medical Monitor.&#xD;
&#xD;
          6. Subject has a history of malignancy except completely excised basal cell carcinoma or&#xD;
             squamous cell carcinoma of the skin.&#xD;
&#xD;
          7. Subject lacks or has poor peripheral venous access.&#xD;
&#xD;
          8. Positive screening result for hepatitis B, hepatitis C and/or HIV serology.&#xD;
&#xD;
          9. Any condition that, in the opinion of the investigator, would compromise the study's&#xD;
             objectives or the well-being of the subject or prevent the subject from meeting the&#xD;
             study requirements.&#xD;
&#xD;
         10. Clinically significant abnormal ECG findings. Particularly, a history or family&#xD;
             history of prolonged QT syndrome (eg, torsade de pointes) or sudden cardiac death.&#xD;
&#xD;
         11. ECG with PR &gt;200 ms, QRS &gt;120 ms, QTcF &gt;450 ms, as assessed by triplicate 12-lead ECG&#xD;
             at the screening visit.&#xD;
&#xD;
         12. Subject has had major surgery, or clinically significant blood loss or elective blood&#xD;
             donation of significant volume (ie, &gt;500 mL) within 60 days of first dose of study&#xD;
             drug; &gt;1 unit of plasma within 7 days of first dose of study drug.&#xD;
&#xD;
         13. Abnormal heart rate, respiratory rate, temperature or blood pressure values outside of&#xD;
             the normal range (evaluated in a semi-recumbent or recumbent position after 5 minutes&#xD;
             of rest). One repeat measurement after an additional 5 minutes of rest is permitted.&#xD;
&#xD;
         14. Evidence of active infection.&#xD;
&#xD;
         15. Unwilling to abstain from alcohol for at least 48 hours prior to the start of dosing&#xD;
             through the study completion visit.&#xD;
&#xD;
         16. History of regular alcohol intake &gt;7 units per week of alcohol for females and &gt;14&#xD;
             units per week for males (one unit is defined as 10 g alcohol) within 3 months of the&#xD;
             screening visit.&#xD;
&#xD;
         17. The subject has a positive screening or Day -1 drugs of abuse screen.&#xD;
&#xD;
         18. The use of concomitant medications, including prescription, over the counter&#xD;
             medications, and herbal medications (such as St. John's Wort [Hypericum perforatum])&#xD;
             within 30 days prior to the first dose of study medication is excluded, unless&#xD;
             approved by the Sponsor's Medical Monitor. Occasional use of ibuprofen/paracetamol/&#xD;
             acetaminophen is permitted.&#xD;
&#xD;
         19. Subject has received an investigational drug (including investigational vaccines) or&#xD;
             used an invasive investigational medical device within 90 days before the planned&#xD;
             study drug.&#xD;
&#xD;
         20. Subject has a history of significant multiple and/or severe allergies, or has had an&#xD;
             anaphylactic reaction or significant intolerability to prescription or&#xD;
             non-prescription drugs or food.&#xD;
&#xD;
         21. Hypersensitivity to the active substances or to any of the excipients of AL-3778,&#xD;
             entecavir or tenofovir disoproxil fumarate.&#xD;
&#xD;
         22. Subject has known allergy to heparin or history of heparin-induced thrombocytopenia.&#xD;
&#xD;
         23. Abnormal biochemistry or hematology laboratory results obtained at screening&#xD;
             determined to be clinically significant by the Investigator. Screening ALT, AST, GGT,&#xD;
             albumin, and total bilirubin must be within normal ranges. Creatine kinase &gt;1.5 x ULN&#xD;
             is exlusionary&#xD;
&#xD;
         24. Unwillingness or inability to comply with the study protocol for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William D Kennedy, MD</last_name>
    <role>Study Director</role>
    <affiliation>Alios Biopharma Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Auckland Clinical Studies</name>
      <address>
        <city>Auckland</city>
        <zip>1010</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christchurch Clinical Studies Trust</name>
      <address>
        <city>Christchurch</city>
        <zip>8011</zip>
        <country>New Zealand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>New Zealand</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>October 13, 2017</last_update_submitted>
  <last_update_submitted_qc>October 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 16, 2017</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>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis B</mesh_term>
    <mesh_term>Hepatitis B, Chronic</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Entecavir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be provided per regulatory requirements.</ipd_description>
  </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/NCT03032536
org study id: AL-3778-1002
secondary id: U1111-1187-4391
nct id: NCT03032536
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, randomized, multi-part study to evaluate the relative oral
      bioavailability of a tablet formulation of AL-3778 (formerly NVR 3-778) administered under
      fasted and fed conditions (Parts 1 and 2) and the drug-drug interaction between AL-3778 and
      entecavir or tenofovir disoproxil fumarate (Part 3).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AL-3778, entecavir, tenofovir: Maximum observed plasma concentration (Cmax)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to last measurable concentration (AUClast)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUC∞)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 1 (Cmax. Day 1)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1
measure: AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 1 (Cmin, Day 1)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1
measure: AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval on Day 1 (AUC0-Τ, Day 1)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1
measure: AL-3778, entecavir, tenofovir: Minimum observed plasma concentration (C_min)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Predose plasma concentrations (C_0-h)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Last observed plasma concentration (C_last)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Time of the maximum observed plasma concentration (T_max)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Time to last measurable plasma concentration (T_last)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Apparent oral clearance (CL/F)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Apparent volume of distribution (Vz/F)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Apparent terminal half-life (t½)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14 and once per day on Day 8, 10, 12, and 22
measure: AL-3778, entecavir, tenofovir: Maximum observed plasma concentration on Day 14 (Cmax. Day 14)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14
measure: AL-3778, entecavir, tenofovir: Minimum observed plasma concentration on Day 14 (Cmin, Day 14)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 14
measure: AL-3778, entecavir, tenofovir: Area under the plasma concentration-time curve from time 0 to dosing interval, tau, on Day 14 (AUC0-Τ, Day 14)
time frame: At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours after dosing on Day 1 and 14
measure: Incidence, nature, and severity of adverse events
time frame: Screening to Day 22
measure: Changes in Vital Signs during and after study drug administration
time frame: Day 1 to Day 22
measure: changes in physical examinations during and after study drug administration
time frame: Day 1 to Day 22
measure: changes in clinical laboratory results during and after study drug administration
time frame: Day 1 to Day 22
measure: changes in electrocardiogram results during and after study drug administration
time frame: Day 1 to Day 22
arm group label: Treatments A, B, C
arm group type: Experimental
description: Part 1: Cross-Over
Treatment A: AL-3778 6 x 100-mg capsules (fasted) once.
Treatment B: AL-3778 2 x 300-mg tablets (fasted) once
Treatment C: AL-3778 2 x 300-mg tablets (high-fat meal) once.
arm group label: Treatments D, E, F
arm group type: Experimental
description: Part 2 (optional): Cross-Over
Treatment D: AL-3778 2×300-mg tablets (fasted) once.
Treatment E: AL-3778 tablet Dose (fasted) once. Dose will match Treatment F dose and will be:
1000mg: 2 x 500-mg OR
800mg: 1 x 300-mg + 1 x 500-mg OR
700mg: 1 x 200-mg + 1 x 500-mg
Treatment F: AL-3778 tablet Dose (high-fat meal) once. Dose will match Treatment E dose and will be:
1000mg: 2 x 500-mg OR
800mg: 1 x 300-mg + 1 x 500-mg OR
700mg: 1 x 200-mg + 1 x 500-mg
arm group label: Treatment G
arm group type: Experimental
description: Part 3: AL-3778 twice daily administered under fasted conditions for 14 days.
Dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:
600mg: 2 x 300-mg OR
1000mg: 2 x 500-mg OR
800mg: 1 x 300-mg + 1 x 500-mg OR
700mg: 1 x 200-mg + 1 x 500-mg
arm group label: Treatment H
arm group type: Active Comparator
description: Part 3: Entecavir 0.5 mg once daily administered under fasted conditions for 14 days
arm group label: Treatment I
arm group type: Experimental
description: Part 3: AL-3778 twice daily with entecavir 0.5 mg once daily both administered under fasted conditions for 14 days.
AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:
600mg: 2 x 300-mg OR
1000mg: 2 x 500-mg OR
800mg: 1 x 300-mg + 1 x 500-mg OR
700mg: 1 x 200-mg + 1 x 500-mg
arm group label: Treatment J
arm group type: Active Comparator
description: Part 3: Tenofovir disoproxil fumarate 300 mg once daily administered under fasted conditions for 14 days
arm group label: Treatment K
arm group type: Experimental
description: Part 3: AL-3778 twice daily and tenofovir disoproxil fumarate 300 mg once daily both administered under fasted conditions for 14 days.
AL-3778 dose will be determined by Part 1 and/or Part 2 and will be one of the following tablet dosages:
600mg: 2 x 300-mg OR
1000mg: 2 x 500-mg OR
800mg: 1 x 300-mg + 1 x 500-mg OR
700mg: 1 x 200-mg + 1 x 500-mg
intervention type: Drug
intervention name: AL-3778
description: AL-3778 tablets or capsules
arm group label: Treatment G
arm group label: Treatment I
arm group label: Treatment K
arm group label: Treatments A, B, C
arm group label: Treatments D, E, F
other name: NVR 3-778, JNJ-63595948, ALS-003778
intervention type: Drug
intervention name: Entecavir
description: Entecavir once daily for 14 days
arm group label: Treatment H
arm group label: Treatment I
intervention type: Drug
intervention name: Tenofovir disoproxil fumarate
description: Tenofovir disoproxil fumarate once daily for 14 days
arm group label: Treatment J
arm group label: Treatment K
other name: Viread
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: William D Kennedy, MD
role: Study Director
affiliation: Alios Biopharma Inc.
facility: 
facility: 
country: New Zealand
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Hepatitis B
mesh term: Hepatitis B, Chronic
mesh term: Hepatitis
mesh term: Tenofovir
mesh term: Entecavir
sharing ipd: Yes
ipd description: Data will be provided per regulatory requirements.