Study to Evaluate Pharmacokinetics, Safety and Tolerability of Dolutegravir and Rilpivirine (JULUCA™) 50 Milligram (mg)/25 mg Tablets in Healthy Subjects of Japanese Descent
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: JULUCA (Dolutegravir and Rilpivirine) 50mg/25mg FDC tablet
Intervention description: JULUCA tablets will be administered orally once daily with a meal. It will be available as a fixed dose combination of Dolutegravir 50mg and Rilpivirine 25mg.
Intervention MeSH terms: Dolutegravir; Rilpivirine; Dolutegravir, rilpivirine drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Dolutegravir, Rilpivirine, HIV infection, Fixed-dose combination, Japanese, Pharmacokinetics

Summary:

      Dolutegravir (DTG), a human immunodeficiency virus (HIV)-1 integrase inhibitor (INI), and
      Rilpivirine (RPV), a non-nucleoside HIV-1 reverse transcriptase inhibitor (NNRTI), are each
      approved in the United States (US), European Union, and other countries for the treatment of
      HIV-1 infection. JULUCA is a combination of Dolutegravir and Rilpivirine indicated for the
      treatment of HIV-1 infection in antiretroviral (ARV) experienced adult subjects who are
      switching from their current antiretroviral treatment to the 2-drug combination. Although,
      the pharmacokinetics (PK), safety and tolerability of DTG/RPV (50 milligram [mg]/25mg)
      fixed-dose combination (FDC) tablets have been extensively studied, these parameters have not
      been assessed exclusively in Japanese subjects. This study will evaluate the
      pharmacokinetics, safety and tolerability of a single dose DTG/RPV 50 mg/25 mg FDC in a
      healthy adult Japanese population to support a post-approval commitment for DTG/RPV 50 mg/25
      mg FDC in Japan.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be 18 to 55 years of age, at the time of signing the informed consent

          -  Subjects who were born in Japan with 4 ethnic Japanese grandparents. Subjects who have
             not lived outside Japan for more than 10 years and who are Japanese passport holders
             (current or expired)

          -  Subjects who are overtly healthy as determined by medical evaluation including medical
             history, physical examination, laboratory tests, and cardiac monitoring (history and
             electrocardiogram [ECG])

          -  Subjects with body weight >=50 kilogram (kg) (110 pounds) for men and >=45kg (99
             pounds) for women and body mass index (BMI) within the range 18.5-31.0 kg per square
             meter (kg/m^2)

          -  Male or female subjects; Male subjects with no specific restrictions

          -  A female subject is eligible to participate if she is not pregnant or breastfeeding,
             and not a woman of childbearing potential (WOCBP)

          -  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

          -  Subjects capable of giving signed informed consent, which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol

        Exclusion Criteria:

          -  Subjects with history of current 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

          -  Subjects with abnormal blood pressure (as determined by the investigator)

          -  Subjects with alanine transaminase (ALT) >1.5 times upper limit of normal (ULN)

          -  Subjects with bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is
             acceptable if bilirubin is fractionated and direct bilirubin <35%)

          -  Subjects with current or chronic history of liver disease, or known hepatic or biliary
             abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)

          -  Subjects with QTcF >460 millisecond (msec)(Based on the average of the
             12-Lead-electrocardiogram (ECG) triplicate readings obtained at Screening) (Note: The
             QTc is the QT interval corrected for heart rate according to Fridericia's formula
             (QTcF), and/or another method, machine-read or manually over-read. The specific
             formula that will be used to determine eligibility and discontinuation for an
             individual subject should be determined prior to initiation of the study. In other
             words, several different formulae cannot be used to calculate the QTc for an
             individual subject and then the lowest QTc value used to include or discontinue the
             subject from the trial)

          -  Subjects with past or intended use of over-the-counter or prescription medication
             including herbal medications within 7 days (or 14 days if the drug is a potential
             enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing. Acetaminophen,
             at doses of <=2 grams per day, is allowed for use any time during the study

          -  Participation in the study would result in loss of blood or blood products in excess
             of 500 milliliter (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 any other clinical study involving an investigational study intervention or
             any other type of medical research

          -  Subjects with presence of Hepatitis B surface antigen (HBsAg) at screening or within 3
             months prior to first dose of study intervention

          -  Subjects with positive Hepatitis C antibody test result at screening or within 3
             months prior to first dose of study intervention (Note: Subjects with positive
             Hepatitis C antibody due to prior resolved disease can be enrolled, only if a
             confirmatory negative Hepatitis C RNA test is obtained)

          -  Subjects with positive Hepatitis C RNA test result at screening or within 3 months
             prior to first dose of study intervention (Note: Test is optional and subjects with
             negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA
             testing)

          -  Subjects with positive pre-study drug or alcohol screen

          -  Subjects with positive human immunodeficiency virus (HIV) antibody test

          -  Subjects with regular use of known drugs of abuse

          -  Subjects with creatinine clearance (CrCL) <60 milliliter per minute

          -  Employment with Janssen, ViiV, GlaxoSmithKline(GSK), or with the Investigator or study
             site, with direct involvement in the proposed study or other studies under the
             direction of that Investigator or study site, as well as family members of the
             employees or the Investigator

          -  Subjects with 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

          -  Subjects with regular alcohol consumption within 6 months prior to the study defined
             as: An average weekly intake of >14 units for males or >7 units for females. One unit
             is equivalent to 8 gram of alcohol: a half-pint (approximately 240mL) of beer, 1 glass
             (125mL) of wine or 1 (25mL) measure of spirits

          -  Subjects with sensitivity to heparin or heparin-induced thrombocytopenia

          -  Subjects with sensitivity to any of the study interventions, or components thereof, or
             drug or other allergy that, in the opinion of the investigator or medical monitor,
             contraindicates participation in the study