Dolutegravir Pediatric Liquid Formulation Study
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Dolutegravir dispersible tablet; Dolutegravir oral suspension; Dolutegravir oral solution
Intervention description: DTG will be available as an oral tablet with dosing strength of 5 mg 2 tablet will be dispersed in water will be administered orally for prescribed regimen.; DTG will be available as an oral suspension with dosing strength of 5 mg per milliliter (ml) or 2 mg per ml with miglyol 812N or ethyl cellulose in miglyol 812N as vehicle for suspension administered orally for prescribed regimen.; DTG will be available as an oral solution with dosing strength of 2 mg per ml will be administered orally for prescribed regimen.
Intervention MeSH terms: Dolutegravir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: The study is non-randomized 6 period, 6 way fixed sequential design.
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Dolutegravir; Human immunodeficiency virus; Sequential study; Dispersible tablet; Suspension; Liquid solution

Summary:

      This is an open-label, single-center, single dose, non-randomized, sequential, fixed-sequence
      study, which will evaluate pharmacokinetics (PK) of dolutegravir (DTG) in healthy adult
      subjects. The study will contain 6 periods with five prototype liquid formulations for
      evaluation in fasted state. In period 1, 2 and 3 single reference dose of 2 dispersible
      tablets of 5 milligram DTG will be administered and at least 2 liquid prototype DTG
      formulations (containing a target total dose of 10mg DTG). There will be a wash-out period of
      7 days between each period. In period 4 through 6, there would be options to evaluate
      additional prototype liquid formulations. The total duration of study will be up to 17 weeks.
      DTG has been found to be safe and effective in adults infected with human immunodeficiency
      virus (HIV). DTG dispersible tablets have been developed primarily for use in children from 4
      weeks to 6 years of age, and a DTG liquid formulation are is being developed to study the
      appropriate dose needed for the HIV-exposed and infected neonatal population in the first
      four weeks of life. Approximately 18 subjects will be enrolled in this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be 18 to 55 years of age inclusive, at the time of signing the informed
             consent.

          -  Subjects who are overtly healthy as determined by medical evaluation including medical
             history, physical examination, laboratory tests, and cardiac evaluation.

          -  Body weight >= 50 kg (110 pounds [lbs]) for men and >=45 kg (99 lbs) for women and
             body mass index (BMI) within the range 18.5-31.0 kilogram per meter square (kg/m^2)
             (inclusive).

          -  Male and female subjects will be part of study. A female subject is eligible to
             participate if she is not pregnant or breastfeeding, and is not a woman of
             childbearing potential (WOCBP).

          -  Additional requirements for pregnancy testing, if needed, during and after study
             intervention; The investigator is responsible for review of medical history, menstrual
             history, and recent sexual activity to decrease the risk for inclusion of a woman with
             an early undetected pregnancy.

          -  Subject should be capable of giving signed informed consent as which includes
             compliance with the requirements and restrictions listed in the informed consent form
             (ICF).

        Exclusion Criteria:

          -  History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
             endocrine, hematological, or neurological disorders capable of significantly altering
             the absorption, metabolism, or elimination of drugs; constituting a risk when taking
             the study intervention; or interfering with the interpretation of data.

          -  Abnormal blood pressure as determined by the investigator.

          -  Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).

          -  Bilirubin >1.5times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin
             is fractionated and direct bilirubin <35%).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  QT correction using Fridericia Formula (QTcF) >450 millisecond (msec)

          -  Past or intended use of over-the-counter or prescription medication (including herbal
             medications) within 7 days prior to dosing. Paracetamol.

          -  History of allergy or sensitivity to DTG.

          -  Participation in the study would result in loss of blood or blood products in excess
             of 500 mL within 56 days.

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day.

          -  Current enrollment or past participation within the last 30 days before signing of
             consent in this or any other clinical study involving an investigational study
             intervention or any other type of medical research.

          -  Presence of Hepatitis B surface antigen (HBsAg), or a positive hepatitis B core
             antibody with a negative hepatitis B surface antibody at screening.

          -  Positive Hepatitis C antibody test result at screening: Subjects with positive
             Hepatitis C antibody due to prior resolved disease can be enrolled, only if a
             confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.

          -  Positive Hepatitis C RNA test result at screening or within 3 months prior to first
             dose of study intervention.

          -  Positive pre-study drug/alcohol screen.

          -  Positive HIV antibody test.

          -  Regular use of known drugs of abuse.

          -  Regular alcohol consumption within one month prior to the study defined as: For the
             United Kingdom an average weekly intake of >14 units for males or females. One unit is
             equivalent to 8 gram (g) of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL)
             of wine or 1 (25 mL) measure of spirits.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6
             months prior to screening.