Bioavailability Study of 10 Milligram (mg) and 5 mg Tablets Versus Conventional Tablets of Dolutegravir
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Conventional dolutegravir 10 mg tablet; Conventional dolutegravir 50 mg tablet; Dispersible dolutegravir 5 mg tablet; Conventional dolutegravir 25 mg tablet
Intervention description: Single dose of five 10 mg DTG tablets will be administered directly to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 1. DTG will be a white, round shaped, biconvex tablet.; Single dose of one 50 mg tablet will be administered directly to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 1. DTG will be a white, round shaped, biconvex tablet.; Single dose of five 5 mg DTG tablets will be administered as dispersed in water or direct to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 2. DTG will be a white, round shaped, biconvex tablet.; Single dose of one 25 mg DTG tablet will be administered directly to mouth with 240 mL of water in the morning to randomized subjects in fasting state present in Part 2. DTG will be a white, round shaped, biconvex tablet.
Intervention MeSH terms: Dolutegravir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Dispersible tablets; Bioavailability; Dolutegravir; Healthy; Conventional tablets

Summary:

      The aim of this cross-over study is to compare the relative bioavailability and
      pharmacokinetic parameters of both 10 mg conventional tablets and 5 mg dispersible tablets of
      dolutegravir (DTG) with that of 25 mg or 50 mg conventional DTG tablets. The study will be
      carried out in 2 parts. Part 1 of the study will be open-label, 2 period designs with a wash
      out period of at least 7 days between the dosing periods. Subjects will be randomized to
      receive either single dose of five 10 mg DTG tablets or one 50 mg DTG tablet in a crossover
      manner in the fasting state. Part 2 of the study will be a 3 period crossover design with a
      wash out period of at least 7 days between the dosing periods. Subjects will be randomized to
      receive either single dose of five 5 mg DTG tablets (administered as dispersed with water or
      directly to mouth) or one 25 mg DTG tablet in a crossover manner in the fasting state.
      Subjects will have a follow-up visit 7-10 days post last dose of study treatment.
      Approximately 14 healthy subjects will participate in Part 1 and approximately 24 healthy
      subjects will participate in Part 2 of the study. The total duration of Part 1 will be
      approximately 7 to 8 weeks and that of part 2 will be approximately 8 to 9 weeks.

      TIVICAY® is a trademark of the GlaxoSmithKline group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Between 18 and 65 years of age inclusive, at the time of signing the informed consent.

          -  Healthy as determined by the investigator or medically qualified designee based on a
             medical evaluation including medical history, physical examination, laboratory tests
             and cardiac evaluation (history and electrocardiogram [ECG]). A subject with a
             clinical abnormality or laboratory parameter(s) which is/are not specifically listed
             in the inclusion or exclusion criteria, outside the reference range for the population
             being studied may be included only if the investigator in consultation with the
             Medical Monitor agree and document that the finding is unlikely to introduce
             additional risk factors and will not interfere with the study procedures.

          -  Body weight >= 50 kilogram (kg) for males and >= 45 kg for females and body mass index
             (BMI) within the range 18.5 - 31.0 kg per meter square (kg/m^2) (inclusive).

          -  Male or female. Non-reproductive potential defined as: Pre-menopausal females with one
             of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion
             procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy;
             Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous
             amenorrhea [in questionable cases a blood sample with simultaneous follicle
             stimulating hormone (FSH) and estradiol levels consistent with menopause]. Females on
             hormone replacement therapy (HRT) and whose menopausal status is in doubt will be
             required to use one of the highly effective contraception methods if they wish to
             continue their HRT during the study. Otherwise, they must discontinue HRT to allow
             confirmation of post-menopausal status prior to study enrolment. Reproductive
             potential and agrees to follow one of the options listed in the Modified List of
             Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential
             (FRP) from 30 days prior to the first dose of study medication and until 2 weeks after
             dosing with study medication and completion of the follow-up visit.

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions.

        Exclusion Criteria:

          -  Alanine amino transferase (ALT) and bilirubin >1.5x Upper limit of normal (ULN)
             (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct
             bilirubin <35 percent).

          -  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 Milliseconds (msec).

          -  Unable to refrain from the use of prescription [that is (i.e. or non-prescription
             drugs, including vitamins, herbal and dietary supplements (including St John's Wort)
             within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives
             (whichever is longer) prior to the first dose of study medication, unless in the
             opinion of the Investigator and ViiV Medical Monitor the medication will not interfere
             with the study procedures or compromise subject safety.

          -  History of regular alcohol consumption within 6 months of the study defined as: an
             average weekly intake of >14 drinks for males or >7 drinks for females. One drink is
             equivalent to 12 gram (g) of alcohol: 12 ounces (360 milliliters [mL]) of beer, 5
             ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine- containing products within 1 month prior to screening.

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or Medical
             Monitor, contraindicates their participation.

          -  Creatinine clearance (CrCL) <90 mL/minute.

          -  A positive hepatitis B surface antigen (HBsAg) or a positive hepatitis B core antibody
             with a negative hepatitis B surface antibody, positive hepatitis C antibody test
             result at screening or within 3 months prior to first dose of study treatment.

          -  A positive pre-study drug/alcohol screen.

          -  A positive test for Human Immuno-deficiency Virus (HIV) antibody.

          -  Where participation in the study would result in donation of blood or blood product in
             excess of 500 mL within 56 days.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day.