Study of Multiple Oral Doses of PF-06835919 in Healthy Adult Japanese Participants
Condition: Healthy
Intervention: PF-06835919; Placebo
Intervention description: PF-06835919 300 mg repeated doses; Placebo repeated doses
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a Phase 1, randomized, double-blind, sponsor-open, placebo-controlled study in healthy adult Japanese participants.
Masking: Double (Participant, Investigator)
Masking description: double
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: NASH, KHK, PF-06835919, Japanese

Summary:

      This is a Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of
      multiple oral doses of PF-06835919 in healthy adult Japanese participants.

      A total of approximately 8 healthy participants will be enrolled in this study. Participants
      will be randomized to 2 groups to receive PF-06835919 or placebo treatment with a
      randomization ratio of 3:1.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of
             signing the ICD.

          2. A Japanese participant is defined as having 4 biological Japanese grandparents who
             were born in Japan.

          3. Male and female participants who are overtly healthy as determined by medical
             evaluation including medical history, physical examination, laboratory tests, and
             cardiovascular tests.

          4. Participants who are willing and able to comply with all scheduled visits, treatment
             plan, laboratory tests, lifestyle considerations, and other study procedures.

          5. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

          6. Capable of giving signed informed consent as described in Appendix 1, which includes
             compliance with the requirements and restrictions listed in the ICD and in this
             protocol.

        Exclusion Criteria:

          1. Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,
             seasonal allergies at the time of dosing).

          2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).

          3. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV,
             HBsAg, HBcAb or HCVAb. Hepatitis B vaccination (positive HBsAb) is allowed.

          4. Other medical or psychiatric condition including recent (within the past year) or
             active suicidal ideation/behavior or laboratory abnormality that may increase the risk
             of study participation or, in the investigator's judgment, make the participant
             inappropriate for the study.

          5. Use of prescription or nonprescription drugs and dietary and herbal supplements within
             7 days or 5 half-lives (whichever is longer) prior to the first dose of study
             intervention (Refer to Section 6.5 for additional details).

          6. Previous administration with an investigational drug within 30 days (or as determined
             by the local requirement) or 5 half-lives preceding the first dose of study
             intervention used in this study (whichever is longer).

          7. A positive urine drug test.

          8. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least
             5 minutes of supine rest: If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the
             BP should be repeated 2 more times and the average of the 3 BP values should be used
             to determine the participant's eligibility.

          9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may
             affect participant safety or interpretation of study results (eg, baseline QTc
             interval >450 msec, complete LBBB, signs of an acute or indeterminate age myocardial
             infarction, ST T interval changes suggestive of myocardial ischemia, second or third
             degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline
             uncorrected QT interval is >450 msec, this interval should be rate corrected using the
             Fridericia method (QTcF) and the resulting QTcF should be used for decision making and
             reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be
             repeated 2 more times and the average of the 3 QTc or QRS values should be used to
             determine the participant's eligibility. Computer interpreted ECGs should be overread
             by a physician experienced in reading ECGs before excluding participants.

         10. Participants with ANY of the following abnormalities in clinical laboratory tests at
             screening, as assessed by the study-specific laboratory and confirmed by a single
             repeat test, if deemed necessary:

               -  AST or ALT level ≥1.25 × ULN;

               -  Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's
                  syndrome may have direct bilirubin measured and would be eligible for this study
                  provided the direct bilirubin level is ≤ ULN.

         11. History of alcohol abuse or binge drinking and/or any other illicit drug use or
             dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5
             (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule,
             alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1
             ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).

         12. Use of tobacco- or nicotine-containing products in excess of the equivalent >5
             cigarettes/day or 2 chews of tobacco per day.

         13. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
             within 60 days prior to dosing.

         14. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
             section of this protocol.

         15. Investigator site staff or Pfizer employees directly involved in the conduct of the
             study, site staff otherwise supervised by the investigator, and their respective
             family members.