Study to Evaluate Safety and Pharmacokinetics of GS-4059 (Tirabrutinib) in Healthy Volunteers and Participants With Rheumatoid Arthritis (RA)

Inclusion Criteria

Part A

• Be a nonsmoker
• Have a calculated body mass index (BMI) from 19 to 30 kg/m^2, inclusive, at screening
• Have a creatinine clearance (CrCl) ≥ 90 mL/min (using the Cockcroft-Gault method based on serum creatinine and actual body weight as measured at screening
• Females of childbearing potential must have a negative serum pregnancy test at screening and clinic admission.
• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs
• Screening laboratory evaluations (hematology including reticulocytes, fasting lipids, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the investigator to have no clinical significance
• Have either a normal 12-lead ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the Sponsor

Part B

• Diagnosis of RA (according to the 1987 American College of Rheumatology (ACR) classification criteria OR a score of ≥ 6 as defined by the ACR/European League Against Rheumatism Classification and Diagnostic Criteria for RA)
• Individuals must have taken methotrexate (MTX) 7.5 to 25 mg/week continuously for at least 12 weeks, with at least 6 weeks of stable dose prior to first study drug dose and throughout study duration.
• Individuals must be receiving folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing and throughout study duration
• Individuals are allowed to remain on anti-malarial therapy, with at least 8 weeks of stable dose prior to first study drug dose
• Use of oral corticosteroids of no more than 10 mg prednisone or its equivalent per day is allowed if dose is stable for at least 28 days prior to first study drug dose
• Nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics (including aspirin ≤ 100 mg daily) are allowed if doses are stable for at least 14 days prior to the first dose of study drug
• Estimated creatinine clearance (CLCr) ≥ 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation
• White blood cells (WBC), neutrophil count, lymphocyte count, and platelet count ≥ 0.75 x lower limit of normal (LLN)
• A negative serum pregnancy test at screening and a negative pregnancy test on the Day 1 visit prior to the first dose of study drug for female individual of child bearing potential.
• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Exclusion Criteria

Part A

• Pregnant or lactating individuals
• Have any serious or active medical or psychiatric illness (including depression) which, in the opinion of the Investigator, would interfere with individual's treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment
• Positive test for drugs of abuse, including alcohol at screening or on Day -1/check-in
• A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen or hepatitis C (HCV) antibody
• Have poor venous access that limits phlebotomy
• Have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins and/or acetaminophen and/o