<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/NCT02185300</url>
  </required_header>
  <id_info>
    <org_study_id>200401</org_study_id>
    <nct_id>NCT02185300</nct_id>
  </id_info>
  <brief_title>Bioavailability Study of a Dolutegravir Dispersible Tablet and Effect of Different Types of Water on the Dispersible Tablet in Healthy Volunteers</brief_title>
  <official_title>A Phase 1, Single Dose, Crossover, Relative Bioavailability Study of a Dolutegravir Dispersible Tablet as Compared to a Dolutegravir Pediatric Granule Formulation and Effect of Different Types of Water on the Dispersible Tablet in Healthy Volunteers(200401)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ViiV Healthcare</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>ViiV Healthcare</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Dolutegravir (DTG) is an HIV-1 integrase inhibitor approved in the United States, Canada,&#xD;
      Australia and EU. A dispersible tablet has been developed for pediatric use as an alternative&#xD;
      to the granule formulation, already in development, and the approved film-coated tablet. This&#xD;
      is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects.&#xD;
      The study will evaluate the relative bioavailability of five dosing regimens: 20 mg DTG&#xD;
      pediatric granules (Treatment A) and of DTG 20 mg dispersible tablets (DTG 20 mg DT) after&#xD;
      dispersed in: low mineral content(LMC) water (Treatment B); dispersed in CONTREX™ mineral&#xD;
      water (Treatment C); dispersed in low mineral content water and consumed after standing for&#xD;
      30 minutes (Treatment D) and dispersed in CONTREX mineral water and consumed after standing&#xD;
      for 30 minutes (Treatment E). Safety evaluations and serial PK samples will be collected&#xD;
      during each treatment period. A follow-up visit will occur 7-14 days after the last dose of&#xD;
      study drug. CONTREX is a trademark of Nestlé Waters Corporation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">September 2014</completion_date>
  <primary_completion_date type="Actual">September 2014</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>Crossover Assignment</intervention_model>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite of pharmacokinetic (PK) parameters following single dose administration of DTG 20 mg DT dispersed in LMC water</measure>
    <time_frame>Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)</time_frame>
    <description>PK parameters include area under the concentration-time curve from time zero extrapolated to infinite time (AUC [0-infinity]) Maximum observed concentration (Cmax) and apparent oral clearance (CL/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in CONTREX mineral water</measure>
    <time_frame>Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)</time_frame>
    <description>PK parameters include AUC (0-infinity), Cmax and CL/F</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water with 30-minute holding</measure>
    <time_frame>Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)</time_frame>
    <description>PK parameters include AUC (0-infinity), Cmax and CL/F</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water</measure>
    <time_frame>Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)</time_frame>
    <description>PK parameters include area under the plasma concentration-time curve from time of dose administration to time of last quantifiable post-dose sample [AUC(0-t)]; observed concentration at 24h post-dose (C24); terminal elimination phase half-life (t½); lag time for absorption (tlag); and time to maximum observed concentration (tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in CONTREX mineral water</measure>
    <time_frame>Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)</time_frame>
    <description>PK parameters include AUC(0-t), C24; t½; tlag; and tmax will be evaluated for DTG 20 mg DT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water with 30-minute holding</measure>
    <time_frame>Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)</time_frame>
    <description>PK parameters include AUC(0-t), C24; t½; tlag; and tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite of PK parameters following single dose administration of DTG 20 mg DT in CONTREX mineral water with 30-minute holding</measure>
    <time_frame>Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)</time_frame>
    <description>PK parameters include AUC (0-infinity), Cmax, CL/F, AUC(0-t); C24; t½; tlag; and tmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Palatability of DTG 20 mg DT</measure>
    <time_frame>Day 1 (Period 1 only)</time_frame>
    <description>Palatability questionnaire containing 11 questions will be administered to each subject within 10 minutes following the dose of DTG (Period 1 only)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety as assessed by number of subjects with adverse events, change from baseline in vital signs and as toxicity grading of clinical laboratory tests</measure>
    <time_frame>Up to 14 weeks</time_frame>
    <description>An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Vital signs include blood pressure and heart rate. Clinical laboratory parameters will include hematology and clinical chemistry</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Infection, Human Immunodeficiency Virus</condition>
  <arm_group>
    <arm_group_label>Sequence ABCDE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered treatments in the sequence ABCDE where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 minutes(mins), re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 minutes, re-dispersed, and then taken by subject</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence BCDEA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered treatments in the sequence BCDEA where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence CDEAB</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered treatments in the sequence CDEAB where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence DEABC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered treatments in the sequence DEABC where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence EABCD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject will be administered treatments in the sequence EABCD where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dolutegravir Pediatric Granules</intervention_name>
    <description>Dolutegravir pediatric granules are supplied as 40 grams bulk bottles containing 0.4% weight by weight of dolutegravir to be reconstituted with 73 mL of purified water to yield a dolutegravir concentration of 1.6 milligram / millilitre. 12.5 mL of reconstituted granules contain 20 mg DTG</description>
    <arm_group_label>Sequence ABCDE</arm_group_label>
    <arm_group_label>Sequence BCDEA</arm_group_label>
    <arm_group_label>Sequence CDEAB</arm_group_label>
    <arm_group_label>Sequence DEABC</arm_group_label>
    <arm_group_label>Sequence EABCD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dolutegravir Dispersible Tablet</intervention_name>
    <description>Dolutegravir is available as 5mg dispersible tablets and can be administered as 4 tablets dispersed in 12.5 mL LMC water and consumed immediately or 4 tablets dispersed in 12.5 mL CONTREX mineral water and consumed immediately or 4 tablets dispersed in 12.5 mL LMC water, allow to stand at room temperature for 30 mins, re-suspend mixture and consumed or 4 tablets dispersed in 12.5 mL CONTREX mineral water, allow to stand at room temperature for 30 mins, re-suspend mixture and consumed</description>
    <arm_group_label>Sequence ABCDE</arm_group_label>
    <arm_group_label>Sequence BCDEA</arm_group_label>
    <arm_group_label>Sequence CDEAB</arm_group_label>
    <arm_group_label>Sequence DEABC</arm_group_label>
    <arm_group_label>Sequence EABCD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Males or females aged between 18 and 65 years of age inclusive, at the time of signing&#xD;
             the informed consent.&#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 agree and documents that the finding is unlikely to introduce additional&#xD;
             risk factors and will not interfere with the study procedures.&#xD;
&#xD;
          -  Body weight +/- 50 kilogram (kg) for males and +/- 45 kg for females and body mass&#xD;
             index (BMI) within the range 18.5 - 31.0 kilogram/square meter (kg/m^2) (inclusive).&#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, bilateral&#xD;
             salpingectomy, bilateral oophorectomy or hysterectomy for this definition,&#xD;
             &quot;documented&quot; refers to the outcome of the investigator's/designee's review of the&#xD;
             subject's medical history for study eligibility, as obtained via a verbal interview&#xD;
             with the subject or from the subject's medical records; or postmenopausal defined as&#xD;
             12 months of spontaneous amenorrhea in questionable cases a blood sample with&#xD;
             simultaneous follicle stimulating hormone (FSH) &gt; 40 milli-international units per&#xD;
             milliliter (mIU/mL) and estradiol &lt; 40 picograms per milliliter (pg/ml) (&lt;147&#xD;
             picomole/liter [pmol/L]) is confirmatory. Child-bearing potential with negative&#xD;
             pregnancy test as determined by serum or urine human chorionic gonadotropin (hCG) test&#xD;
             at screening and prior to dosing AND agrees to use one of the contraception methods&#xD;
             for an appropriate period of time (as determined by the product label or investigator)&#xD;
             prior to the start of dosing to sufficiently minimize the risk of pregnancy at that&#xD;
             point. Female subjects must agree to use contraception until 5 days post-last dose OR&#xD;
             have only same-sex partners, when this is her preferred and usual lifestyle.&#xD;
&#xD;
          -  Capable of giving written informed consent, which includes compliance with the&#xD;
             requirements and restrictions listed in the consent form.&#xD;
&#xD;
          -  Alanine transaminase (ALT), alkaline phosphatase and bilirubin &lt;= 1.5x upper limit of&#xD;
             the normal range (ULN) (isolated bilirubin &gt;1.5xULN is acceptable if bilirubin is&#xD;
             fractionated and direct bilirubin &lt;35%). A single repeat from screening to period 1,&#xD;
             day -1 is allowed for eligibility determination.&#xD;
&#xD;
          -  QT duration corrected for heart rate (QTc) &lt; 450 millisecond (msec), using Bazett&#xD;
             Correction Formula, QT correction using Bazett Formula (QTcB). A single repeat from&#xD;
             screening to period 1, day -1 is allowed for eligibility determination.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  A positive test for Human Immunodeficiency Virus (HIV) antibody.&#xD;
&#xD;
          -  Pregnant females as determined by positive serum or urine hCG test at screening or&#xD;
             prior to dosing.&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as: an&#xD;
             average weekly intake of &gt;14 drinks for males or &gt;7 drinks for females. One drink is&#xD;
             equivalent to 12 grams (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL)&#xD;
             of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.&#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;
          -  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;
          -  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;
          -  Lactating females.&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody&#xD;
             result within 3 months of screening&#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;
          -  Regular use of tobacco- or nicotine-containing products within 60 days prior to&#xD;
             screening.&#xD;
&#xD;
          -  Unable to refrain from the use of prescription 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;
          -  The subject's systolic blood pressure is outside the range of 90-140 millimeters of&#xD;
             mercury (mmHg), or diastolic pressure is outside the range of 45-90 mmHg, or heart&#xD;
             rate is outside the range of 50-100 beats per minute (bpm) for female subjects or&#xD;
             45-110 bpm for male subjects. A single repeat from screening to period 1, day -1 is&#xD;
             allowed for eligibility determination.&#xD;
&#xD;
          -  Exclusion criteria for screening electrocardiogram (ECG) (a single repeat is allowed&#xD;
             for eligibility determination): Heart rate - For males &lt;45 and &gt;110 bpm and for&#xD;
             females &lt;50 and &gt;100 bpm, PR Interval &lt;120 and &gt;220 msec, QRS duration &lt;70 and &gt;120&#xD;
             msec, QTc interval (Bazett) &gt;450 msec, evidence of previous myocardial infarction&#xD;
             (Does not include ST segment changes associated with repolarization), any clinically&#xD;
             significant arrhythmia which, in the opinion of the investigator and GSK Medical&#xD;
             Monitor, will interfere with the safety for the individual subject, or any conduction&#xD;
             abnormality with the exception of 1st degree atrioventricular block or incomplete&#xD;
             right bundle branch block&#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>ViiV Healthcare</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2014</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>November 26, 2014</last_update_submitted>
  <last_update_submitted_qc>November 26, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 2, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GSK1349572</keyword>
  <keyword>granule</keyword>
  <keyword>pediatric</keyword>
  <keyword>CONTREX mineral water</keyword>
  <keyword>free-acid</keyword>
  <keyword>chelating</keyword>
  <keyword>cations</keyword>
  <keyword>divalent</keyword>
  <keyword>dolutegravir</keyword>
  <keyword>dispersible tablet</keyword>
  <keyword>relative bioavailability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dolutegravir</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/NCT02185300
org study id: 200401
nct id: NCT02185300
lead sponsor: 
collaborator: 
has dmc: No
Dolutegravir (DTG) is an HIV-1 integrase inhibitor approved in the United States, Canada,
      Australia and EU. A dispersible tablet has been developed for pediatric use as an alternative
      to the granule formulation, already in development, and the approved film-coated tablet. This
      is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects.
      The study will evaluate the relative bioavailability of five dosing regimens: 20 mg DTG
      pediatric granules (Treatment A) and of DTG 20 mg dispersible tablets (DTG 20 mg DT) after
      dispersed in: low mineral content(LMC) water (Treatment B); dispersed in CONTREX™ mineral
      water (Treatment C); dispersed in low mineral content water and consumed after standing for
      30 minutes (Treatment D) and dispersed in CONTREX mineral water and consumed after standing
      for 30 minutes (Treatment E). Safety evaluations and serial PK samples will be collected
      during each treatment period. A follow-up visit will occur 7-14 days after the last dose of
      study drug. CONTREX is a trademark of Nestlé Waters Corporation.
allocation: Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: Composite of pharmacokinetic (PK) parameters following single dose administration of DTG 20 mg DT dispersed in LMC water
time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
description: PK parameters include area under the concentration-time curve from time zero extrapolated to infinite time (AUC [0-infinity]) Maximum observed concentration (Cmax) and apparent oral clearance (CL/F)
measure: Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in CONTREX mineral water
time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
description: PK parameters include AUC (0-infinity), Cmax and CL/F
measure: Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water with 30-minute holding
time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
description: PK parameters include AUC (0-infinity), Cmax and CL/F
measure: Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water
time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
description: PK parameters include area under the plasma concentration-time curve from time of dose administration to time of last quantifiable post-dose sample [AUC(0-t)]; observed concentration at 24h post-dose (C24); terminal elimination phase half-life (t½); lag time for absorption (tlag); and time to maximum observed concentration (tmax)
measure: Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in CONTREX mineral water
time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
description: PK parameters include AUC(0-t), C24; t½; tlag; and tmax will be evaluated for DTG 20 mg DT
measure: Composite of PK parameters following single dose administration of DTG 20 mg DT dispersed in LMC water with 30-minute holding
time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
description: PK parameters include AUC(0-t), C24; t½; tlag; and tmax
measure: Composite of PK parameters following single dose administration of DTG 20 mg DT in CONTREX mineral water with 30-minute holding
time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose), Day 2 (24 hours) and Day 3 (48 hours)
description: PK parameters include AUC (0-infinity), Cmax, CL/F, AUC(0-t); C24; t½; tlag; and tmax
measure: Palatability of DTG 20 mg DT
time frame: Day 1 (Period 1 only)
description: Palatability questionnaire containing 11 questions will be administered to each subject within 10 minutes following the dose of DTG (Period 1 only)
measure: Safety as assessed by number of subjects with adverse events, change from baseline in vital signs and as toxicity grading of clinical laboratory tests
time frame: Up to 14 weeks
description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Vital signs include blood pressure and heart rate. Clinical laboratory parameters will include hematology and clinical chemistry
arm group label: Sequence ABCDE
arm group type: Experimental
description: Subject will be administered treatments in the sequence ABCDE where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 minutes(mins), re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 minutes, re-dispersed, and then taken by subject
arm group label: Sequence BCDEA
arm group type: Experimental
description: Subject will be administered treatments in the sequence BCDEA where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject
arm group label: Sequence CDEAB
arm group type: Experimental
description: Subject will be administered treatments in the sequence CDEAB where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject
arm group label: Sequence DEABC
arm group type: Experimental
description: Subject will be administered treatments in the sequence DEABC where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject
arm group label: Sequence EABCD
arm group type: Experimental
description: Subject will be administered treatments in the sequence EABCD where, A = Single dose of DTG 20 mg of the pediatric granule formulation reconstituted with purified water; B = Single dose of DTG 20 mg DT dispersed in LMC water; C = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water; D= Single dose of DTG 20 mg DT dispersed in LMC water, held for 30 mins, re-dispersed, and then taken by subject; E = Single dose of DTG 20 mg DT dispersed in CONTREX mineral water, held for 30 mins, re-dispersed, and then taken by subject
intervention type: Drug
intervention name: Dolutegravir Pediatric Granules
description: Dolutegravir pediatric granules are supplied as 40 grams bulk bottles containing 0.4% weight by weight of dolutegravir to be reconstituted with 73 mL of purified water to yield a dolutegravir concentration of 1.6 milligram / millilitre. 12.5 mL of reconstituted granules contain 20 mg DTG
arm group label: Sequence ABCDE
arm group label: Sequence BCDEA
arm group label: Sequence CDEAB
arm group label: Sequence DEABC
arm group label: Sequence EABCD
intervention type: Drug
intervention name: Dolutegravir Dispersible Tablet
description: Dolutegravir is available as 5mg dispersible tablets and can be administered as 4 tablets dispersed in 12.5 mL LMC water and consumed immediately or 4 tablets dispersed in 12.5 mL CONTREX mineral water and consumed immediately or 4 tablets dispersed in 12.5 mL LMC water, allow to stand at room temperature for 30 mins, re-suspend mixture and consumed or 4 tablets dispersed in 12.5 mL CONTREX mineral water, allow to stand at room temperature for 30 mins, re-suspend mixture and consumed
arm group label: Sequence ABCDE
arm group label: Sequence BCDEA
arm group label: Sequence CDEAB
arm group label: Sequence DEABC
arm group label: Sequence EABCD
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: ViiV Healthcare
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Dolutegravir