<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/NCT03277755</url>
  </required_header>
  <id_info>
    <org_study_id>CR108294</org_study_id>
    <secondary_id>64294178HPC1020</secondary_id>
    <nct_id>NCT03277755</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Odalasvir and AL-335 Alone and in Combination With Simeprevir in Participants With Moderately Impaired Hepatic Function</brief_title>
  <official_title>An Open-label Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Odalasvir and AL-335 Alone and in Combination With Simeprevir in Subjects With Moderately Impaired Hepatic Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</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>
      The purpose of this study is to evaluate the pharmacokinetics (PK) of AL-335, odalasvir (ODV)&#xD;
      and its metabolites ALS-022399 and ALS-022227, after a single oral dose of ODV and AL-335&#xD;
      respectively, in participants with moderately impaired hepatic function compared to&#xD;
      participants with normal hepatic function. Also to evaluate the steady-state PK of AL-335 and&#xD;
      its metabolites ALS-022399 and ALS-022227, ODV and simeprevir (SMV) after multiple oral doses&#xD;
      of the combination of AL-335+ODV+SMV, in participants with moderately impaired hepatic&#xD;
      function compared to participants with normal hepatic function.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Development program of JNJ-4178 was discontinued.&#xD;
  </why_stopped>
  <start_date type="Anticipated">September 11, 2017</start_date>
  <completion_date type="Anticipated">December 22, 2017</completion_date>
  <primary_completion_date type="Anticipated">December 22, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolites ALS-022399 and ALS-022227</measure>
    <time_frame>Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose</time_frame>
    <description>Cmax is defined as maximum observed plasma concentration of AL-335 and its metabolites ALS-022399 and ALS-022227.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of AL-335 and its Metabolites ALS-022399 and ALS-022227</measure>
    <time_frame>Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose</time_frame>
    <description>The AUC (0-last) is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335 and its Metabolites ALS-022399 and ALS-022227</measure>
    <time_frame>Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose</time_frame>
    <description>The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C (last)/ lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Maximum Observed Plasma Concentration (Cmax) of Odalasvir (ODV)</measure>
    <time_frame>Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose</time_frame>
    <description>Cmax is defined as maximum observed plasma concentration of ODV.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of ODV</measure>
    <time_frame>Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose</time_frame>
    <description>The AUC (0-last) is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV</measure>
    <time_frame>Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose</time_frame>
    <description>The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC (last) and C (last)/lambda(z); wherein AUC (last) is area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Maximum Observed Plasma Concentration (Cmax) of Simeprevir (SMV)</measure>
    <time_frame>Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose</time_frame>
    <description>Cmax is defined as maximum observed plasma concentration of SMV.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC[0-24]) of SMV</measure>
    <time_frame>Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose</time_frame>
    <description>The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Maximum Observed Plasma Concentration (Cmax) of ODV</measure>
    <time_frame>Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose</time_frame>
    <description>Cmax is defined as maximum observed plasma concentration of ODV.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours Postdose (AUC[0-24]) of ODV</measure>
    <time_frame>Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose</time_frame>
    <description>The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV</measure>
    <time_frame>Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose</time_frame>
    <description>The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C (last)/ lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolites ALS-022399 and ALS-022227</measure>
    <time_frame>Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose</time_frame>
    <description>Cmax is defined as maximum observed plasma concentration of AL-335 and its metabolites ALS-022399 and ALS-022227.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) Postdose of AL-335 and its metabolites ALS-022399 and ALS-022227</measure>
    <time_frame>Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose</time_frame>
    <description>The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1 and 2: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to 30-35 days after last drug intake (approximately up to 102 days)</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Hepatic Impairment</condition>
  <arm_group>
    <arm_group_label>Cohort1:Participants With Moderately Impaired Hepatic Function</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants With moderately impaired hepatic function will receive a single oral dose of AL-335 800 milligram (mg) (2 tablets of 400 mg AL-335) on Day 1 of Part 1 followed by a single oral dose of odalasvir (ODV) 25 mg (1 tablet of 25 mg ODV) on Day 8 of Part 1 and a combination of AL-335 800 mg (2 tablets of 400 mg AL-335) + ODV 25 mg (1 tablet of 25 mg ODV) + simeprevir (SMV) 75 mg (1 capsule of 75 mg SMV) once daily on Day 1 to 14 of Part 2. There will be a washout period between Part 1 and Part 2 of at least 14 days. Day 8 of Part 1 will be the start of the washout period. Prior to the start of study drug administration in Part 2, a safety review will be performed by the Sponsor.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Participants With Normal Hepatic Function</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with normal hepatic function will receive a single oral dose of AL-335 800 mg (2 tablets of 400 mg AL-335) on Day 1 of Part 1 followed by a single oral dose of ODV 25 mg (1 tablet of 25 mg ODV) on Day 8 of Part 1 and a combination of AL-335 800 mg (2 tablets of 400 mg AL-335) + ODV 25 mg (1 tablet of 25 mg ODV) + SMV 75 mg (1 capsule of 75 mg SMV) once daily on Day 1 to 14 of Part 2. There will be a washout period between Part 1 and Part 2 of at least 14 days. Day 8 of Part 1 will be the start of the washout period. Prior to the start of study drug administration in Part 2, a safety review will be performed by the Sponsor.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AL-335 800 mg</intervention_name>
    <description>Participants will receive AL-335 800 mg (2 tablets of 400 mg AL-335) single oral dose on Day 1 of part 1 and in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.</description>
    <arm_group_label>Cohort 2: Participants With Normal Hepatic Function</arm_group_label>
    <arm_group_label>Cohort1:Participants With Moderately Impaired Hepatic Function</arm_group_label>
    <other_name>JNJ-64146212</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ODV 25 mg</intervention_name>
    <description>Participants will receive ODV 25 mg (1 tablet of 25 mg ODV) single oral dose on Day 8 of part 1 and in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.</description>
    <arm_group_label>Cohort 2: Participants With Normal Hepatic Function</arm_group_label>
    <arm_group_label>Cohort1:Participants With Moderately Impaired Hepatic Function</arm_group_label>
    <other_name>JNJ-64289901</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SMV 75 mg</intervention_name>
    <description>Participants will receive SMV 75 mg in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.</description>
    <arm_group_label>Cohort 2: Participants With Normal Hepatic Function</arm_group_label>
    <arm_group_label>Cohort1:Participants With Moderately Impaired Hepatic Function</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must have a body mass index (BMI; weight in kilogram (kg) divided by the&#xD;
             square of height in meters) of 18.0 to 35.0 kilogram per meter square (kg/m^2)&#xD;
             extremes included, and a body weight not less than 50.0 kg&#xD;
&#xD;
          -  Participant must have a normal 12-lead electrocardiogram (ECG) (based on the mean&#xD;
             value of triplicate ECG parameters) consistent with normal cardiac conduction and&#xD;
             function at screening, as defined in the protocol&#xD;
&#xD;
          -  Absence of findings indicative of hepatocellular carcinoma in an ultrasonography&#xD;
             determined within 90 days prior to screening (or between screening and Day -1 of Part&#xD;
             1 of the study)&#xD;
&#xD;
          -  Contraceptive use by women should be consistent with local regulations regarding the&#xD;
             use of contraceptive methods for participants participating in clinical studies; a&#xD;
             female participant with non childbearing potential must be; a) postmenopausal, or b)&#xD;
             surgically sterile. Participant of childbearing potential must; a) have a negative&#xD;
             highly sensitive serum (beta human chorionic gonadotropin [beta hCG]) pregnancy test&#xD;
             at screening and a negative urine beta hCG pregnancy test at baseline (Day -1), and b)&#xD;
             not get pregnant from screening until at least 60 days after the end of treatment by&#xD;
             adhering to one of the acceptable methods of birth control to avoid pregnancy&#xD;
&#xD;
          -  Contraceptive use by men should be consistent with local regulations regarding the use&#xD;
             of contraceptive methods for participant participating in clinical studies: A male&#xD;
             participant: a) must either be surgically sterile, or b) must not be heterosexually&#xD;
             active from baseline until at least 60 days after the end of treatment or c) must be&#xD;
             practicing an acceptable method of birth control from baseline until at least 60 days&#xD;
             after the end of treatment, if heterosexually active with a woman of childbearing&#xD;
             potential&#xD;
&#xD;
          -  Participants with moderately impaired hepatic function (Cohort 1) must meet the&#xD;
             following additional inclusion criteria:&#xD;
&#xD;
               1. Participants must have a stable hepatic function as confirmed by serum bilirubin,&#xD;
                  serum albumin, prothrombin, ascites, and hepatic encephalopathy status measured&#xD;
                  during screening and those measured within 24 hours prior to first study drug&#xD;
                  administration on Day 1 in Part 1&#xD;
&#xD;
               2. Participants must be hepatically impaired with a Class B classification as&#xD;
                  defined by the Child Pugh classification of severity of liver disease, that is, a&#xD;
                  total Child-Pugh score of 7 to 9, inclusive.&#xD;
&#xD;
          -  Participants with normal hepatic function (Cohort 2) must meet the additional&#xD;
             inclusion criteria to be enrolled in the study: Participants must have a normal&#xD;
             hepatic function as confirmed by serum bilirubin, serum albumin, prothrombin, ascites,&#xD;
             and hepatic encephalopathy status measured during screening and those measured within&#xD;
             24 hours prior to first study drug administration on Day 1 in Part 1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has either: a history of renal insufficiency (estimated creatinine&#xD;
             clearance lesser than (&lt;) 90 milliliter per minute per 1.73 meter square&#xD;
             (mL/min/1.73m^2) for estimated glomerular filtration rate [eGFR] according to the&#xD;
             Chronic Kidney Disease Epidemiology Collaboration [CKD- EPI] equation) 18, or serum&#xD;
             creatinine grade 1 or greater than (&gt;) 1.1* upper limit of normal [ULN]) during&#xD;
             screening&#xD;
&#xD;
          -  Participant has any condition for which, in the opinion of the Investigator,&#xD;
             participation would not be in the best interest of the participant (example,&#xD;
             compromise the well-being), or that could prevent, limit, or confound the&#xD;
             protocol-specified assessments&#xD;
&#xD;
          -  Participant with any history of clinically significant skin disease such as, but not&#xD;
             limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticarial&#xD;
&#xD;
          -  Participant has known allergies, hypersensitivity, or intolerance to simeprevir (SMV),&#xD;
             odalasvir (ODV), or AL 335, or their excipients&#xD;
&#xD;
          -  Participant who smokes more than 10 cigarettes or 2 cigars or 2 pipes per day from&#xD;
             within 90 days before screening until the end of the study&#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>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>October 10, 2017</last_update_submitted>
  <last_update_submitted_qc>October 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2017</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>Adafosbuvir</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03277755
org study id: CR108294
secondary id: 64294178HPC1020
nct id: NCT03277755
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the pharmacokinetics (PK) of AL-335, odalasvir (ODV)
      and its metabolites ALS-022399 and ALS-022227, after a single oral dose of ODV and AL-335
      respectively, in participants with moderately impaired hepatic function compared to
      participants with normal hepatic function. Also to evaluate the steady-state PK of AL-335 and
      its metabolites ALS-022399 and ALS-022227, ODV and simeprevir (SMV) after multiple oral doses
      of the combination of AL-335+ODV+SMV, in participants with moderately impaired hepatic
      function compared to participants with normal hepatic function.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolites ALS-022399 and ALS-022227
time frame: Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose
description: Cmax is defined as maximum observed plasma concentration of AL-335 and its metabolites ALS-022399 and ALS-022227.
measure: Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of AL-335 and its Metabolites ALS-022399 and ALS-022227
time frame: Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose
description: The AUC (0-last) is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.
measure: Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335 and its Metabolites ALS-022399 and ALS-022227
time frame: Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose
description: The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C (last)/ lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of Odalasvir (ODV)
time frame: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
description: Cmax is defined as maximum observed plasma concentration of ODV.
measure: Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of ODV
time frame: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
description: The AUC (0-last) is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.
measure: Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV
time frame: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
description: The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC (last) and C (last)/lambda(z); wherein AUC (last) is area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
measure: Part 2: Maximum Observed Plasma Concentration (Cmax) of Simeprevir (SMV)
time frame: Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose
description: Cmax is defined as maximum observed plasma concentration of SMV.
measure: Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC[0-24]) of SMV
time frame: Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose
description: The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.
measure: Part 2: Maximum Observed Plasma Concentration (Cmax) of ODV
time frame: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose
description: Cmax is defined as maximum observed plasma concentration of ODV.
measure: Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours Postdose (AUC[0-24]) of ODV
time frame: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose
description: The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.
measure: Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV
time frame: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose
description: The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C (last)/ lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
measure: Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolites ALS-022399 and ALS-022227
time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose
description: Cmax is defined as maximum observed plasma concentration of AL-335 and its metabolites ALS-022399 and ALS-022227.
measure: Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) Postdose of AL-335 and its metabolites ALS-022399 and ALS-022227
time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose
description: The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.
measure: Part 1 and 2: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability
time frame: Up to 30-35 days after last drug intake (approximately up to 102 days)
description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.
arm group label: Cohort1:Participants With Moderately Impaired Hepatic Function
arm group type: Experimental
description: Participants With moderately impaired hepatic function will receive a single oral dose of AL-335 800 milligram (mg) (2 tablets of 400 mg AL-335) on Day 1 of Part 1 followed by a single oral dose of odalasvir (ODV) 25 mg (1 tablet of 25 mg ODV) on Day 8 of Part 1 and a combination of AL-335 800 mg (2 tablets of 400 mg AL-335) + ODV 25 mg (1 tablet of 25 mg ODV) + simeprevir (SMV) 75 mg (1 capsule of 75 mg SMV) once daily on Day 1 to 14 of Part 2. There will be a washout period between Part 1 and Part 2 of at least 14 days. Day 8 of Part 1 will be the start of the washout period. Prior to the start of study drug administration in Part 2, a safety review will be performed by the Sponsor.
arm group label: Cohort 2: Participants With Normal Hepatic Function
arm group type: Experimental
description: Participants with normal hepatic function will receive a single oral dose of AL-335 800 mg (2 tablets of 400 mg AL-335) on Day 1 of Part 1 followed by a single oral dose of ODV 25 mg (1 tablet of 25 mg ODV) on Day 8 of Part 1 and a combination of AL-335 800 mg (2 tablets of 400 mg AL-335) + ODV 25 mg (1 tablet of 25 mg ODV) + SMV 75 mg (1 capsule of 75 mg SMV) once daily on Day 1 to 14 of Part 2. There will be a washout period between Part 1 and Part 2 of at least 14 days. Day 8 of Part 1 will be the start of the washout period. Prior to the start of study drug administration in Part 2, a safety review will be performed by the Sponsor.
intervention type: Drug
intervention name: AL-335 800 mg
description: Participants will receive AL-335 800 mg (2 tablets of 400 mg AL-335) single oral dose on Day 1 of part 1 and in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.
arm group label: Cohort 2: Participants With Normal Hepatic Function
arm group label: Cohort1:Participants With Moderately Impaired Hepatic Function
other name: JNJ-64146212
intervention type: Drug
intervention name: ODV 25 mg
description: Participants will receive ODV 25 mg (1 tablet of 25 mg ODV) single oral dose on Day 8 of part 1 and in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.
arm group label: Cohort 2: Participants With Normal Hepatic Function
arm group label: Cohort1:Participants With Moderately Impaired Hepatic Function
other name: JNJ-64289901
intervention type: Drug
intervention name: SMV 75 mg
description: Participants will receive SMV 75 mg in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.
arm group label: Cohort 2: Participants With Normal Hepatic Function
arm group label: Cohort1:Participants With Moderately Impaired Hepatic Function
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
country: United States
responsible party type: Sponsor
mesh term: Adafosbuvir