Study in Subjects With Rheumatoid Arthritis to Evaluate the Effect of a Single Dose of Olokizumab on the Pharmacokinetics of Substrates for CYP1A2, CYP2C9, CYP2C19 and CYP3A4

Inclusion Criteria: 1. Subjects willing and able to give voluntary informed consent and sign an Informed Consent Form (ICF) 2. Male subjects and their female partners and female subjects of childbearing potential must agree to adhere to the contraceptive requirements for the study Female subjects of non-childbearing potential must be: • Surgically sterile (i.e. bilateral tubal ligation or removal of both ovaries and/or uterus at least 6 months prior to first dosing), or • Naturally postmenopausal (spontaneous cessation of menses) for at least 24 consecutive months prior to first dosing, with a follicle stimulating hormone level at screening of ≥40 mIU/mL. 3. Body mass index of 18 kg/m2 to 29.9 kg/m2, inclusive, and body weight of 55 kg to 110 kg, inclusive, if male, and 45 kg to 100 kg, inclusive, if female. 4. Subjects must have a diagnosis of adult onset RA classified by the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 revised classification criteria for RA (Aletaha et al, 2010) for at least 12 weeks prior to Screening. If the subject was previously diagnosed according to ACR 1987 criteria, the Investigator may classify the subject per ACR 2010 retrospectively, based on medical history, and using available source data. 5. Subjects must have received Methotrexate (MTX), sulfasalazine, or hydroxychloroquine for at least 12 weeks prior to Day 1 and in stable dose for at least 6 weeks prior to Day 1 without significant Adverse events (AEs). Stable doses of MTX should be 10 mg to 25 mg weekly with folic acid (at least 5 mg weekly or equivalent). No significant side effects based on the Investigator's judgment should be observed during treatment by these agents. The maximum allowed doses of sulfasalazine and hydroxychloroquine are: 1. Sulfasalazine: 3 g per day 2. Hydroxychloroquine: 400 mg per day Note: The doses should remain stable and not be changed from the time of signing the ICF until the end of the treatment period (EOT, Day 29). 6. Subjects must have an increased CRP at Screening (of ≥1.2 × ULN). 7. Female subjects of childbearing potential must have negative pregnancy test at Screening and throughout the study until the end of study (EOS) (Day 161). Exclusion Criteria: 1. Diagnosis of any other inflammatory arthritis or systemic inflammatory disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). Osteoarthritis is classified as a degenerative disease rather than an inflammatory disease. 2. Subjects with Steinbrocker Class III or IV functional capacity (incapacitated, largely, or wholly bed ridden, or confined to a wheelchair, with little, or no self-care). 3. Prior exposure to any licensed or investigational compound directly or indirectly targeting IL-6 or IL-6R within 12 months of Day 1. 4. Treatment with DMARDs other than MTX, hydroxychloroquine, or sulfasalazine. Treatment with the following DMARDs are not allowed within the specified time period prior to Day 1: 1. 4 weeks for azathioprine, cyclosporine, chloroquine, gold, penicillamine, minocycline, or doxycycline. 2. 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to Day 1: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours or activated charcoal at a dosage of 50 grams 4 times a day for at least 24 hours. 3. 24 weeks for cyclophosphamide. 5. Treatment with any cell-depleting therapies including anti-cluster of differentiation (CD)20 or investigational agents (eg, CAMPATH®, anti-CD4, anti-CD5, anti-CD3, and anti-CD19) with the exception of rituximab. Treatment with rituximab is not allowed within 6 months of Day 1. 6. Treatment with Tumor necrosis factor alpha inhibitor (TNFi) (including investigational proposed or licensed biosimilars) or any other biologic therapy for the treatment of RA within 12 weeks of Day 1. 7. Use of parenteral or intra-articular glucocorticoids within 4 weeks prior to Day 1. 8. Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 4 weeks prior to Day 1. 9. Use of indomethacin and ketorolac; other nonsteroidal anti-inflammatory drugs (NSAIDs) (with the exception of aspirin, see below) must be taken at a stable dose and route of administration for at least 2 weeks prior to Day 1. 10. Female subjects of nonchildbearing potential taking hormone replacement therapy within 4 weeks prior to Day 1. 11. Vaccination with live vaccines in the 6 weeks prior to Day 1 or planned vaccination with live vaccines during the study. 12. Participation in any other investigational drug study within 30 days or 5 times the t1/2 of the investigational drug, whichever is longer, prior to Day 1. 13. Use of aspirin or other antiplatelet agents and anticoagulants including warfarin in the 4 weeks prior to Day 1. 14. Has received any prescription or nonprescription drugs or other products (eg, herbal preparations, food products) known to be inhibitors/inducers of CYP3A4, CYP2C9, CYP2C19, or CYP1A2 within 4 weeks prior to Day 1 and for the duration of the study up to the EOT (Day 29) Visit. The use of MTX, as described in inclusion criterion #5, is permitted. 15. Use of any herbal preparations (including foods or beverages containing herbal preparations), dietary supplements, or natural medications within 14 days of Day 1. 16. Has received midazolam and/or omeprazole (or esomeprazole) within 14 days of Day 1. 17. Excessive intake of caffeine (more than 5 cups of coffee or equivalent per day) and the inability to abstain from caffeine-containing drinks and foods from 2 days prior to each cocktail administration and while inpatient (Day -1 to Day 2 and Day 21 to Day 23, respectively). 18. Poor metabolizers of CYP2C9 (genotype \*2/\*2, \*2/\*3, \*3/\*3) or CYP2C19 (genotype \*2/\*2, \*2/\*3, \*3/\*3), ultra-rapid metabolizers of CYP2C19 (\*17/\*17), or high sensitivity to warfarin (VKORCI genotype AA). 19. Previous participation (enrolled) in this study or another study of OKZ in case of receiving at least one OKZ dose. 20. Abnormal laboratory values as defined below. If, in the opinion of the Investigator, exclusionary results are due to laboratory error or a transient condition, these tests may be repeated once during Screening. a. Creatinine level ≥1.5 mg/dL (132 µmol/L) for females or ≥2.0 mg/dL (177 µmol/L) for males. b. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) level ≥1.5 × ULN. c. Platelets \<150 × 10\^9/L (\<150,000/mm3). d. White blood cell count \<3.0 × 10\^9/L. e. Neutrophil count \<2.0 × 10\^9/L (\<2000 mm3). f. Hemoglobin level ≤95 g/L. g. Glycosylated hemoglobin (HbA1c) level ≥8%. h. International normalized ratio above the ULN (Normal range: 0.80 or 0.90 to 1.20, males and females of all ages). 21. Subjects with concurrent viral hepatitis B or C infection as detected by blood tests at Screening (eg, positive for hepatitis B surface antigen (HBsAg), hepatitis B DNA (HBV DNA) or hepatitis C virus antibody (HCV Ab)). 1. HBV DNA to be tested only in anti-hepatitis B core antigen (anti-HBc) positive subjects. 2. Subject who is positive for hepatitis B surface antibody (anti-HBs) and total antiHBc but negative for HBsAg and HBV DNA, will be eligible upon qualified specialist (i.e. hepatologist) consultation with documented conclusion no additional risk is suspected for the subject. 3. Subject who is positive for hepatitis B surface antibody (anti-HBs) but negative for HBsAg and total anti-HBc, will be eligible with no additional consultation. 22. Subjects with human immunodeficiency virus (HIV) infection. 23. Subjects with: 1. Suspected or confirmed current active tuberculosis (TB) disease or a history of active TB disease. 2. Close contact (ie, sharing the same household or other enclosed environment, such as a social gathering place, workplace or facility, for extended periods during the day) with an individual with active TB within 1.5 years prior to Screening. 3. History of untreated latent TB infection (LTBI), regardless of QuantiFERON-TB Gold Plus interferon-gamma release assay (IGRA) result at Screening. 4. Positive IGRA result at Screening. If indeterminate, the IGRA can be repeated once during Screening. If there is a second indeterminate result, the subject will be excluded. 24. Concurrent malignancy or a history of malignancy within the last 5 years (with the exception of successfully treated carcinoma of the cervix in situ or successfully treated basal cell carcinoma or squamous cell carcinoma not less than 1 year prior to Screening \[and no more than 3 excised nonmelanoma skin cancers within the last 5 years prior to Screening\]). 25. Subjects with a history of major bleeding, bleeding tendencies (such as any prior gastrointestinal bleeding and recent ulceration of gastrointestinal track, congenital and acquired disorders by hemostasis), or other clinically significant predisposition to bleeding according to the physician's judgment. 26. Subjects with a history or presence of severe cardiovascular conditions such as stroke, transient ischemic attack, or myocardial infarction in medical history. 27. Uncompensated congestive heart failure, or Class III or IV heart failure defined by the New York Heart Association classification. 28. Untreated, uncontrolled, or resistant arterial hypertension Grade 2 to 3 (systolic blood pressure (BP) \>160 mm Hg and/or diastolic BP \>100 mm Hg, based on the mean of 3 readings). If hypertension is not controlled, subjects should be excluded, and not allowed for rescreening. 29. Uncontrolled diabetes mellitus (based on the Investigator's judgment). 30. Subjects with a history or presence of any other cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, dermatological, neurological, psychiatric, hematological, or immunologic/immunodeficiency disorder(s) or any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, contraindicate subject participation in the clinical study, or clinically significant enough in the opinion of the Investigator to alter the disposition of the study treatment, or constitute a possible confounding factor for assessment of safety of the study treatment.. 31. Subjects with gastrointestinal (GI) resection (eg, partial or total gastrectomy) likely to interfere with absorption of study treatment. 32. Subjects with any infection requiring any anti-infective therapy (eg, antibiotic, antiviral, or antifungal therapy) in the 4 weeks prior to Day 1, or serious or recurrent infection with history of hospitalization in the 6 months prior to Day 1 or active infection at Day 1. 33. Subjects with evidence of disseminated herpes zoster infection, zoster encephalitis, meningitis, or other nonself-limited herpes zoster infections in the 6 months prior to Day 1. 34. Subjects with planned surgery during the study (up to and including the EOT Visit,\[Day 29\]) or surgery ≤4 weeks prior to Screening and from which the subject has not fully recovered, as judged by the Investigator. 35. Subjects with diverticulitis or other symptomatic GI conditions that might predispose the subject to perforations, including subjects with a history of such predisposing conditions (eg, diverticulitis, GI perforation, or ulcerative colitis). 36. History of chronic alcohol or drug abuse or consumption of more than 21 units (male subjects) or 14 units (female subjects) of alcohol a week (unit = 1 glass of wine \[125 mL\] = 1 measure of spirits = ½ pint of beer) as judged by the Investigator. 37. Current smokers or those who have smoked or used nicotine products within the previous 3 months prior to Screening. 38. Subjects with a known hypersensitivity or contraindication to any component of the cocktail drugs or OKZ. 39. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies. 40. Any self-reported symptoms of influenza-like or COVID-19 like illness in the 14 days preceding Screening OR Day 1 as per the Investigators assessment. Symptoms related to COVID-19 include, but are not limited to: a. Respiratory symptoms (eg, sore throat, nasal congestion, post-nasal discharge, wheezing, cough, dyspnea, and bronchial breath sounds); b. Non-respiratory symptoms, such as gastrointestinal symptoms (eg, nausea, vomiting, and diarrhea), neurologic symptoms (eg, anosmia, ageusia, headache), myalgia or fatigue. 41. Active SARS-CoV-2 infection as confirmed by reverse transcription polymerase chain reaction (RT-PCR) or/and positive serology at Screening. 42. Known exposure to an individual with confirmed COVID-19 or SARS-CoV-2 infection within 2 weeks before Screening OR Day 1. 43. History of COVID-19 infection in the previous 3 months before Day 1 or with sever or critical illness ever. Note: The subject can be enrolled if all of the following criteria are fulfill: 1. had non-sever or non-critical COVID-19 infection more than 3 months before Day 1; 2. fully recovered as per official medical records which should be documented as a source document (mild sequelae of the previous infection such as dry cough, weakness should be resolved by the time of Screening); 3. there are no any concerns that the subject is infections to others; 4. there are no any other local guidelines/requirements with regards of this group of subjects. 44\. Those subjects who have been at high risk of exposure before Screening, including but not limited to: Close contacts of confirmed COVID-19 cases, anyone who had to self-isolate as a result of a symptomatic household member, frontline healthcare professionals working in accident and emergency (A\&E), ICU and other higher risk areas. 45\. Individuals currently working with high risk of exposure to SARS-CoV-2 (eg, active healthcare workers or emergency response personnel having direct interactions with or providing direct care to patients). 46\. Pregnancy and breastfeeding. 47\. Other medical or psychiatric conditions or laboratory abnormalities that may increase potential risk associated with study participation and administration of study treatment, or that may affect study results interpretation and, as per the Investigator's judgment. 48\. Subject's unwillingness or inability to follow the procedures outlined in the protocol. 49\. Employees or relatives of the Sponsor, Contract Research Organization, or the study center personnel.