<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/NCT02184637</url>
  </required_header>
  <id_info>
    <org_study_id>200951</org_study_id>
    <nct_id>NCT02184637</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Pharmacokinetics of a Single Dose of Tafenoquine Co-administered With Either Artemether + Lumefantrine or Dihydroartemisinin + Piperaquine Tetraphosphate</brief_title>
  <official_title>A Five-cohort, Randomized, Open-label, Parallel-group Study to Evaluate the Pharmacokinetics of a Single Dose of Tafenoquine (SB252263) 300mg When Co-administered With the Artemisinin-based Combination Therapies (ACT) Artemether + Lumefantrine (AL) and Dihydroartemisinin + Piperaquine Tetraphosphate (DHA+PQP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medicines for Malaria Venture</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a single-centre, 5-cohort, randomized open-label, parallel-group study in&#xD;
      healthy volunteer subjects. This study aims to provide sufficient pharmacokinetic (PK)&#xD;
      evidence to support the safe usage of Tafenoquine (TQ) in studies and markets where the&#xD;
      Artemisinin-based Combination Therapies (ACTs) are the standard of care for patients with&#xD;
      Plasmodium vivax malaria (i.e., co administration with TQ). The objective of this study is to&#xD;
      assess the pharmacokinetics, safety and tolerability of TQ when co-administered with the&#xD;
      chosen ACTs (AL and DHA + PQP), administered concomitantly in healthy subjects. Specifically,&#xD;
      the study will evaluate whether there are drug-drug interactions between TQ and each of the&#xD;
      ACTs and if these interactions are considered to be clinically significant. The co-primary&#xD;
      objectives of this study are to characterize both the effects of a 300 milligram (mg) single&#xD;
      dose of TQ on the pharmacokinetics; changes in (area under the concentration-time curve from&#xD;
      0 to time t) AUC (0-t), AUC (0-infinity), and maximum observed concentration (Cmax) of each&#xD;
      of the two Artemisinin-based Combination Therapies (ACT) according to their prescribed dose&#xD;
      when co-administered as well as the effects of the ACTs on the PK of TQ.&#xD;
&#xD;
      A total of 120 subjects (24 subjects in each of 5 cohorts) are planned to be enrolled in&#xD;
      order to ensure a target sample size of at least 22 subjects completing the study per cohort.&#xD;
      All subjects will arrive in the unit at least 24 hours prior to dosing and be discharged&#xD;
      after 72-hour post first dose assessments have been completed. Subjects will return for&#xD;
      outpatient visits on Days 7, 14, 21, 28, and 56 after first dose.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2014</start_date>
  <completion_date type="Actual">April 8, 2015</completion_date>
  <primary_completion_date type="Actual">April 8, 2015</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>Ratios of Geometric mean (90% [confidence interval] CI) for DHA+PQP AUC and Cmax for treatment groups: Cohort 1 (TQ + DHA+PQP) versus (vs.) cohort 3 (DHA+PQP)</measure>
    <time_frame>Up to Day 56</time_frame>
    <description>Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratios of geometric mean [90% CI] for A/DHA/L AUC and Cmax for treatment groups: Cohort 2 (TQ + AL) vs. cohort 4 (AL).</measure>
    <time_frame>Up to Day 56</time_frame>
    <description>Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratios of geometric mean [90% CI] for TQ AUC and Cmax for treatment groups: Cohort 1 (TQ + DHA+PQP) vs. cohort 5 (TQ).</measure>
    <time_frame>Up to Day 56</time_frame>
    <description>Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratios of geometric mean [90% CI] for TQ AUC and Cmax for treatment groups: Cohort 2 (TQ + AL) vs. cohort 5 (TQ).</measure>
    <time_frame>Up to Day 56</time_frame>
    <description>Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic endpoints including changes in time to Cmax (Tmax) and apparent terminal phase half-life (t½) for TQ, as data permit.</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic endpoints including changes in Tmax and t½ for each of the ACTs, as data permit.</measure>
    <time_frame>Up to Day 56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in safety laboratory measures (including haemoglobin change from baseline [mean of pre-dose and Day-1 results])</measure>
    <time_frame>Day -1 to Day 28</time_frame>
    <description>Laboratory assessments will include haematology, clinical chemistry and urinalysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of adverse events (AEs)</measure>
    <time_frame>Day -1 to Day 56</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum change from baseline in QT interval corrected for heart rate by Fridericia's formula (QTcF) for all cohorts</measure>
    <time_frame>Day 1 to Day 56</time_frame>
    <description>The baseline measurement will be the average of the triplicate measurements taken on pre-dose Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcF at 52-hours post-first dose for subjects who receive DHA+PQP (cohort 1 and 3)</measure>
    <time_frame>Pre-dose (Day 1) and 52-hours post-dose ( Day 3)</time_frame>
    <description>The baseline measurement will be the average of the triplicate measurements taken on pre-dose Day 1.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Malaria, Vivax</condition>
  <arm_group>
    <arm_group_label>Cohort 1- TQ w/DHA+PQP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tafenoquine (TQ) will be co-administered with Dihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) on Day 1. DHA+PQP alone will be administered at 24 hours (h) (Day 2) and 48 h (Day 3) post first dose administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 - TQ w/AL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tafenoquine co-administered with Artemether + Lumefantrine (AL) on Day 1. AL alone will be administered at 8h (Day 1), 24h and 36h (Day 2), 48h and 60 h (Day 3) post first dose administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3 - DHA+PQP alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) will be administered on Day 1 and at 24 hours (Day 2) and 48 hours (Day 3) post first dose administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4 - AL alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Artemether + Lumefantrine will be administered on Day 1 and 8h, 24 and 36h (Day 2), 48h and 60 h(Day 3) post first dose administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 5 - TQ alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single dose of Tafenoquine will be administered on Day 1</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tafenoquine</intervention_name>
    <description>A dark pink, capsule-shaped, film-coated tablet containing 150mg tafenoquine. To be administered orally</description>
    <arm_group_label>Cohort 1- TQ w/DHA+PQP</arm_group_label>
    <arm_group_label>Cohort 2 - TQ w/AL</arm_group_label>
    <arm_group_label>Cohort 5 - TQ alone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dihydroartemisinin + Piperaquine tetraphosphate</intervention_name>
    <description>White, oblong, biconvex, film-coated tablet with a break-line and marked on one side with two &quot;σ&quot; letters containing 320 mg piperaquine tetraphosphate (as the tetrahydrate; PQP) and 40 mg dihydroartemisinin (DHA). To be administered orally</description>
    <arm_group_label>Cohort 1- TQ w/DHA+PQP</arm_group_label>
    <arm_group_label>Cohort 3 - DHA+PQP alone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Artemether + Lumefantrine</intervention_name>
    <description>Light yellow, round tablet with &quot;NC&quot; debossed on one side and &quot;CG&quot; on the other, containing 20 mg artemether and 120 mg lumefantrine. To be administered orally</description>
    <arm_group_label>Cohort 2 - TQ w/AL</arm_group_label>
    <arm_group_label>Cohort 4 - AL alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy as determined by a responsible and experienced physician, based on a medical&#xD;
             evaluation including medical history, physical examination, laboratory tests and&#xD;
             cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s),&#xD;
             which is/are not specifically listed in the inclusion or exclusion criteria, outside&#xD;
             the reference range for the population being studied may be included only if the&#xD;
             Investigator and GlaxoSmithKline (GSK) Medical Monitor agree and document that the&#xD;
             finding is unlikely to introduce additional risk factors and will not interfere with&#xD;
             the study procedures. Subjects whose laboratory values are outside the normal ranges&#xD;
             will be excluded from enrolment.&#xD;
&#xD;
          -  Male or female aged between 18 and 65 years of age inclusive, at the time of signing&#xD;
             the informed consent.&#xD;
&#xD;
          -  Alanine Aminotransferase (ALT), alkaline phosphatase and bilirubin &lt;=1.5x Upper Limit&#xD;
             of Normal (ULN) (isolated bilirubin &gt;1.5xULN is acceptable if bilirubin is&#xD;
             fractionated and direct bilirubin &lt;35%).&#xD;
&#xD;
          -  QTcF &lt;440 milliseconds (msec) based on averaged corrected QT interval (QTc) values of&#xD;
             triplicate electrocardiogram (ECGs) obtained over a brief recording period at&#xD;
             screening and no history of additional risk factors for Torsades des Pointes (e.g.,&#xD;
             heart failure or family history of Long QT Syndrome).&#xD;
&#xD;
          -  A female subject is eligible to participate if she is of: Non-childbearing potential&#xD;
             defined as pre-menopausal females with a documented tubal ligation or hysterectomy&#xD;
             [for this definition, &quot;documented&quot; refers to the outcome of the&#xD;
             investigator's/designee's review of the subject's medical history for study&#xD;
             eligibility, as obtained via a verbal interview with the subject or from the subject's&#xD;
             medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in&#xD;
             questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH)&#xD;
             &gt; 40 milli-international units per (MIU)/ millilitre (mL) and estradiol &lt;40 picograms&#xD;
             (pg)/mL (&lt;147 picomoles (pmol)/liter [L]) is confirmatory]. [Females on hormone&#xD;
             replacement therapy (HRT) and whose menopausal status is in doubt will be required to&#xD;
             use one of the contraception methods, if they wish to continue their HRT during the&#xD;
             study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal&#xD;
             status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse&#xD;
             between the cessation of therapy and the blood draw; this interval depends on the type&#xD;
             and dosage of HRT. Following confirmation of their post-menopausal status, they can&#xD;
             resume use of HRT during the study without use of a contraceptive method.];&#xD;
             Child-bearing potential with negative pregnancy test as determined by serum or urine&#xD;
             human chorionic gonadotropin (hCG) test at screening or prior to dosing AND Agrees to&#xD;
             use one of the contraception methods for an appropriate period of time (as determined&#xD;
             by the product label or investigator) prior to the start of dosing to sufficiently&#xD;
             minimize the risk of pregnancy at that point. Female subjects must agree to use&#xD;
             contraception until 56-days post first dose. OR has only same-sex partners, when this&#xD;
             is her preferred and usual lifestyle.&#xD;
&#xD;
          -  Body Mass Index (BMI) within the range 18.5 to 31.0 kilogram/square meter (kg/m^2)&#xD;
             (inclusive) and body weight between &gt;=36kilogram (kg) and &lt;=100kg.&#xD;
&#xD;
          -  Capable of giving written informed consent, which includes compliance with the&#xD;
             requirements and restrictions listed in the consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The subject's average triplicate (at screening after approximately 5 minutes at rest&#xD;
             in the semi-supine position) systolic blood pressure is outside the range of 80-140&#xD;
             millimeters of mercury (mmHg), or diastolic blood pressure is outside the range of&#xD;
             45-90mmHg or heart rate is outside the range of 40-100 beats per minute (bpm).&#xD;
&#xD;
          -  Where participation in the study would result in donation of blood or blood products&#xD;
             in excess of 500 mL within a 56-day period.&#xD;
&#xD;
          -  Lactating females.&#xD;
&#xD;
        Criteria Based Upon Medical Histories:&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as: an&#xD;
             average weekly intake of &gt;21 units for males or &gt;14 units for females. One unit is&#xD;
             equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1&#xD;
             glass (125 mL) of wine or 1 (25 mL) measure of spirits.&#xD;
&#xD;
          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.&#xD;
&#xD;
          -  History of sensitivity to any of the study medications, or components thereof or a&#xD;
             history of drug or other allergy that, in the opinion of the investigator or GSK&#xD;
             Medical Monitor, contraindicates their participation.&#xD;
&#xD;
          -  History of thalassaemia; or current or past history of methemoglobinemia or&#xD;
             methemoglobin percentage above the reference range at screening.&#xD;
&#xD;
          -  The subject has participated in a clinical trial and has received an investigational&#xD;
             product within the following time period prior to the first dosing day in the current&#xD;
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the&#xD;
             investigational product (whichever is longer).&#xD;
&#xD;
          -  Exposure to more than four new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Consumption of Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic&#xD;
             citrus fruits, or grapefruit hybrids from 7 days prior to the first dose of study&#xD;
             medication.&#xD;
&#xD;
          -  Use of prescription (except female contraception) or non-prescription drugs, including&#xD;
             vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or&#xD;
             14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is&#xD;
             longer) prior to the first dose of study medication, unless in the opinion of the&#xD;
             Investigator and GSK Medical Monitor the medication will not interfere with the study&#xD;
             procedures or compromise subject safety.&#xD;
&#xD;
        Criteria Based Upon Diagnostic Assessments:&#xD;
&#xD;
          -  Subjects with a haemoglobin values outside the lower limit of normal range. A single&#xD;
             repeat is allowed for eligibility determination.&#xD;
&#xD;
          -  Documented phenotypic Glucose-6-phosphate dehydrogenase (G6PD) deficiency, determined&#xD;
             by a quantitative assay of enzyme activity. Defined as &lt;70% of locally defined median.&#xD;
&#xD;
          -  Potassium &lt;4.0 millimoles (mmol)/L and Magnesium &lt;1.8 mg/ deciliter (dL). Subjects&#xD;
             with potassium (K) and magnesium (Mg) values below these screening or on Day-1 may be&#xD;
             treated with oral supplementation and be retested for eligibility prior to dosing.&#xD;
&#xD;
          -  Cotinine levels indicative of smoking or history or regular use of tobacco- or&#xD;
             nicotine-containing products within 30 days prior to screening.&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody&#xD;
             result within 3 months of screening&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  A positive test for human immunodeficiency virus (HIV) antibody.&#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>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 3, 2014</study_first_submitted>
  <study_first_submitted_qc>July 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>July 10, 2017</last_update_submitted>
  <last_update_submitted_qc>July 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Malaria</keyword>
  <keyword>Artemisinin-based Combination Therapies (ACT)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
    <mesh_term>Malaria, Vivax</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lumefantrine</mesh_term>
    <mesh_term>Artemether</mesh_term>
    <mesh_term>Piperaquine</mesh_term>
    <mesh_term>Artenimol</mesh_term>
    <mesh_term>Tafenoquine</mesh_term>
    <mesh_term>Artemether, Lumefantrine Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>200951</doc_id>
      <doc_type>Dataset Specification</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>200951</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>200951</doc_id>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>200951</doc_id>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>200951</doc_id>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>200951</doc_id>
      <doc_type>Annotated Case Report Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>200951</doc_id>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
  </study_docs>
  <!-- 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/NCT02184637
org study id: 200951
nct id: NCT02184637
lead sponsor: 
collaborator: 
has dmc: No
This will be a single-centre, 5-cohort, randomized open-label, parallel-group study in
      healthy volunteer subjects. This study aims to provide sufficient pharmacokinetic (PK)
      evidence to support the safe usage of Tafenoquine (TQ) in studies and markets where the
      Artemisinin-based Combination Therapies (ACTs) are the standard of care for patients with
      Plasmodium vivax malaria (i.e., co administration with TQ). The objective of this study is to
      assess the pharmacokinetics, safety and tolerability of TQ when co-administered with the
      chosen ACTs (AL and DHA + PQP), administered concomitantly in healthy subjects. Specifically,
      the study will evaluate whether there are drug-drug interactions between TQ and each of the
      ACTs and if these interactions are considered to be clinically significant. The co-primary
      objectives of this study are to characterize both the effects of a 300 milligram (mg) single
      dose of TQ on the pharmacokinetics; changes in (area under the concentration-time curve from
      0 to time t) AUC (0-t), AUC (0-infinity), and maximum observed concentration (Cmax) of each
      of the two Artemisinin-based Combination Therapies (ACT) according to their prescribed dose
      when co-administered as well as the effects of the ACTs on the PK of TQ.

      A total of 120 subjects (24 subjects in each of 5 cohorts) are planned to be enrolled in
      order to ensure a target sample size of at least 22 subjects completing the study per cohort.
      All subjects will arrive in the unit at least 24 hours prior to dosing and be discharged
      after 72-hour post first dose assessments have been completed. Subjects will return for
      outpatient visits on Days 7, 14, 21, 28, and 56 after first dose.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ratios of Geometric mean (90% [confidence interval] CI) for DHA+PQP AUC and Cmax for treatment groups: Cohort 1 (TQ + DHA+PQP) versus (vs.) cohort 3 (DHA+PQP)
time frame: Up to Day 56
description: Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.
measure: Ratios of geometric mean [90% CI] for A/DHA/L AUC and Cmax for treatment groups: Cohort 2 (TQ + AL) vs. cohort 4 (AL).
time frame: Up to Day 56
description: Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.
measure: Ratios of geometric mean [90% CI] for TQ AUC and Cmax for treatment groups: Cohort 1 (TQ + DHA+PQP) vs. cohort 5 (TQ).
time frame: Up to Day 56
description: Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.
measure: Ratios of geometric mean [90% CI] for TQ AUC and Cmax for treatment groups: Cohort 2 (TQ + AL) vs. cohort 5 (TQ).
time frame: Up to Day 56
description: Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.
measure: Pharmacokinetic endpoints including changes in time to Cmax (Tmax) and apparent terminal phase half-life (t½) for TQ, as data permit.
time frame: Up to Day 56
measure: Pharmacokinetic endpoints including changes in Tmax and t½ for each of the ACTs, as data permit.
time frame: Up to Day 56
measure: Changes in safety laboratory measures (including haemoglobin change from baseline [mean of pre-dose and Day-1 results])
time frame: Day -1 to Day 28
description: Laboratory assessments will include haematology, clinical chemistry and urinalysis.
measure: Frequency of adverse events (AEs)
time frame: Day -1 to Day 56
description: An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
measure: Maximum change from baseline in QT interval corrected for heart rate by Fridericia's formula (QTcF) for all cohorts
time frame: Day 1 to Day 56
description: The baseline measurement will be the average of the triplicate measurements taken on pre-dose Day 1.
measure: Change from baseline in QTcF at 52-hours post-first dose for subjects who receive DHA+PQP (cohort 1 and 3)
time frame: Pre-dose (Day 1) and 52-hours post-dose ( Day 3)
description: The baseline measurement will be the average of the triplicate measurements taken on pre-dose Day 1.
arm group label: Cohort 1- TQ w/DHA+PQP
arm group type: Experimental
description: Tafenoquine (TQ) will be co-administered with Dihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) on Day 1. DHA+PQP alone will be administered at 24 hours (h) (Day 2) and 48 h (Day 3) post first dose administration.
arm group label: Cohort 2 - TQ w/AL
arm group type: Experimental
description: Tafenoquine co-administered with Artemether + Lumefantrine (AL) on Day 1. AL alone will be administered at 8h (Day 1), 24h and 36h (Day 2), 48h and 60 h (Day 3) post first dose administration.
arm group label: Cohort 3 - DHA+PQP alone
arm group type: Experimental
description: Dihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) will be administered on Day 1 and at 24 hours (Day 2) and 48 hours (Day 3) post first dose administration
arm group label: Cohort 4 - AL alone
arm group type: Experimental
description: Artemether + Lumefantrine will be administered on Day 1 and 8h, 24 and 36h (Day 2), 48h and 60 h(Day 3) post first dose administration
arm group label: Cohort 5 - TQ alone
arm group type: Experimental
description: A single dose of Tafenoquine will be administered on Day 1
intervention type: Drug
intervention name: Tafenoquine
description: A dark pink, capsule-shaped, film-coated tablet containing 150mg tafenoquine. To be administered orally
arm group label: Cohort 1- TQ w/DHA+PQP
arm group label: Cohort 2 - TQ w/AL
arm group label: Cohort 5 - TQ alone
intervention type: Drug
intervention name: Dihydroartemisinin + Piperaquine tetraphosphate
description: White, oblong, biconvex, film-coated tablet with a break-line and marked on one side with two "σ" letters containing 320 mg piperaquine tetraphosphate (as the tetrahydrate; PQP) and 40 mg dihydroartemisinin (DHA). To be administered orally
arm group label: Cohort 1- TQ w/DHA+PQP
arm group label: Cohort 3 - DHA+PQP alone
intervention type: Drug
intervention name: Artemether + Lumefantrine
description: Light yellow, round tablet with "NC" debossed on one side and "CG" on the other, containing 20 mg artemether and 120 mg lumefantrine. To be administered orally
arm group label: Cohort 2 - TQ w/AL
arm group label: Cohort 4 - AL alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United States
responsible party type: Sponsor
mesh term: Malaria
mesh term: Malaria, Vivax
mesh term: Lumefantrine
mesh term: Artemether
mesh term: Piperaquine
mesh term: Artenimol
mesh term: Tafenoquine
mesh term: Artemether, Lumefantrine Drug Combination
sharing ipd: Yes
ipd description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 