Phase I Study of GSK2982772 in Japanese Healthy Male Participants
Condition: Autoimmune Diseases
MeSH terms: Autoimmune Diseases
Intervention: GSK2982772; Placebo
Intervention description: GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route; Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Study will comprise of four TPs, each of at least 7 days in duration with subjects in-house for 4 nights (through 72 hours after the first dose). During each TP, subjects will be admitted to the unit, day before dosing and will be discharged after completion of 72 hours post-dose assessments. dose will be administered TID, in an ascending manner. Every individual subject will receive placebo and GSK2982772 (60, 120,240 mg TID) as per assigned sequence. For TID dosing, GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hour (the second dosing) and 14 hour (the third dosing) on Day 1 in each period. On Day 1, subjects will fast 8hour overnight prior to first dose. breakfast will be served approximately 2hour after first dose. Lunch and dinner will be served between 2 to 3hour prior to second and third doses, respectively. A washout of atleast 7-days between the TP doses for each individual subject.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: It is a double-blinded study, where the subjects, investigators and the site-staff will be blinded.
Enrollment: 13.0
Sex: Male
Minimum age: 20 Years
Maximum age: 64 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Sentinel-dosing; GSK2982772; Japnese; Dose-ascending; Crossover; Healthy

Summary:

      The study plans to enroll approximately 12 subjects. The main objective of the study is to
      assess the safety, tolerability and pharmacokinetics (PK) of the three times a day (TID),
      dosing of GSK2982772, in Japanese healthy male subjects. The study will comprise of four
      study periods each at least 7 days in duration with subjects in-house for 4 nights (through
      72 hrs after the first dose). During each treatment period (TP), subjects will be admitted to
      the unit the day before dosing and will be discharged after completion of the 72 hours
      post-dose assessments. There will be a washout of atleast 7-days between the TP doses for
      each individual, post which there will be 7-days follow-up. The dose range proposed in this
      study is based on a low starting dose, which will be escalated to the highest dose that is
      intended for the Phase 2b dose range study. The decision to proceed to the next dose-level,
      of GSK2982772 within the study will be made by principal investigator and GSK Medical Monitor
      per each dosing periods. The study duration is approximately 22 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be 20 to 64 years of age inclusive, at the time of signing the informed
             consent.

          -  Healthy as determined by the Investigators based on a medical evaluation including
             medical history, physical examination, neurological examination, laboratory tests, and
             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 Investigators in
             consultation with the GSK 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) and body mass index (BMI) within the range 18.5-24.9
             kg/meter square (inclusive).

          -  Japanese male subjects must agree to use contraception as detailed in protocol during
             the treatment period and until follow up visit.

          -  Capable of giving informed consent as described in the protocol.

        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 treatment; or interfering with the interpretation of data.

          -  Abnormal blood pressure as determined by the investigators.

          -  Symptomatic herpes zoster within 3 months prior to screening.

          -  Evidence of active or latent Tuberculosis (TB) as documented by medical history and
             examination, chest X-rays (anterior and lateral), and TB testing (T Spot. TB)

          -  ALT >1.5 times upper limit of normal (ULN).

          -  Bilirubin >1.5 times 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).

          -  History of active infections within 14 days of first receiving study medication.

          -  Corrected Q-T interval (QTc) obtained using the Fridericia's formula (QTcF) > 450
             millisecond.

          -  History or diagnosis of obstructive sleep apnoea, or a significant respiratory
             disorder. Childhood asthma that was fully resolved is permitted.

          -  History of active Suicidal Ideation Behavior within the past 6 months or any history
             of attempted suicide in a subject's lifetime.

          -  History or current evidence of febrile seizures, epilepsy, convulsions, significant
             head injury, or other significant neurologic conditions.

          -  Past or intended use of over-the-counter or prescription medication including herbal
             medications within 14 days prior to dosing; live vaccine(s) within 1 month prior to
             screening, or plans to receive such vaccines during the study.

          -  History of donation of blood or blood products >= 400 mL within 3 months or >= 200 mL
             within 1 month prior to screening.

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day.

          -  The subject has participated in a other clinical study or other medical research
             within 4 months prior to the first dosing day in the current study.

          -  Subject is positive Serological test for syphilis Rapid Plasma Reagin [RPR] and
             Treponema pallidum [TP]), Tuberculosis, human immunodeficiency virus (HIV)
             Antigen/Antibody, Hepatitis B surface antigen (HbsAg), Hepatitis C virus (HCV)
             antibody, or Human T-cell leukemia virus type 1 (HTLV-1) antibody at screening.

          -  Positive pre-study drug screen.

          -  Regular use of known drugs of abuse.

          -  Regular alcohol consumption within 6 months prior to the study defined as: for an
             average weekly intake of > 14 units for males. One unit is equivalent to 350 mL of
             beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.

          -  Smoking or history or regular use of tobacco- or nicotine-containing products within 6
             months prior to screening.

          -  Sensitivity to any of the study treatments, or components thereof, or drug or other
             allergy that, in the opinion of the investigators or GSK Medical Monitor,
             contraindicates participation in the study.