[No standalone website (unbranded, no questionnaire)] A Study of Subjects With Psoriatic Arthritis to Investigate the Effectiveness of Adalimumab Introduction Compared With Methotrexate Dose Escalation (CONTROL)

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Condition

Rheumatoid Arthritis

Treatment type

Interventional

Investigational product

Caffeine

Phase

Phase 1

Sponsor

R-Pharm

ClinicalTrials.gov identifier

NCT04246762

Study number

CL04041026

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About the study

This is a Phase 1, open-label, 3-period, single-sequence, crossover study to evaluate potential effects of olokizumab on pharmacokinetics (PK) of selected CYP450 substrates in subjects with Rheumatoid Arthritis (RA).

Who can take part?

You may be eligible to participate in the study if you meet the following criteria:

Inclusion criteria
  1. ICF) 2. Female subjects of non-child bearing 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
  2. 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 60 kg to 110 kg, inclusive, if male, and 50 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/
  3. EULAR) 2010 revised classification criteria for RA (Aletaha et al,
  4. 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. 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).
Exclusion criteria
  1. 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 (
  2. TNFi) (including investigational proposed or licensed
  3. 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
  4. equivalent) or change in dosage within 4 weeks prior to Day 1. 9. Use of indomethacin and ketorolac; other nonsteroidal anti-inflammatory drugs (
  5. NSAIDs) (with the exception of aspirin, see
  6. 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
  7. 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
  8. 29) Visit. See Appendix 4 for a list of inhibitors and inducers. 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
  9. esomeprazole) within 14 days of Day 1. 17. Excessive intake of caffeine (more than 5 cups of coffee or equivalent per
  10. 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 *1/*2, *1/*3, *2/*2, *2/*3, *3/*
  11. 3) or CYP2C19 (genotype *2/*2, *2/*3, *3/*3), ultra-rapid metabolizers of CYP2C19 (*17/*17), or high sensitivity to warfarin (VKORCI genotype AG and AA). 19. Previous participation (
  12. enrolled) in this study or another study of OKZ 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. 1. Creatinine level ≥1.5 mg/dL (132 µmol/
  13. L) for females or ≥2.0 mg/dL (177 µmol/
  14. L) for males. 2. Alanine aminotransferase (
  15. ALT) or Aspartate aminotransferase (
  16. AST) level ≥1.5 × ULN. 3. Platelets <150 × 109/L (<150,000/mm3). 4. White blood cell count <3.0 × 109/L. 5. Neutrophil count <2.0 × 109/L (<2000 mm3). 6. Hemoglobin level ≤110 g/L. 7. Glycosylated hemoglobin (
  17. HbA1c) level ≥8%. 8. 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 acute or chronic viral hepatitis B or C infection as detected by blood tests at Screening (eg, positive for hepatitis B surface antigen (HBsAg), antihepatitis B core antigen [anti-HBc], or hepatitis C virus antibody (HCV Ab)). a. Subjects who are positive for Hepatitis B surface antibody (anti-
  18. HBs) but negative for HBsAg and total anti-HBc, will be eligible. 22. Subjects with human immunodeficiency virus (
  19. HIV) infection. 23. Subjects with: 1. Suspected or confirmed current active tuberculosis (
  20. 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
  21. 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 (
  22. IGRA) result at Screening. 4. Positive (
  23. 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 II, 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(
  24. 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 (
  25. GI) resection (eg, partial or total
  26. gastrectomy) likely to interfere with absorption of study treatment. 32. Subjects with any infection requiring any anti-infective therapy (eg, antibiotic, antiviral, or antifungal
  27. 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
  28. subjects) or 14 units (female
  29. subjects) of alcohol a week (unit = 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of
  30. 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 monoclonal antibodies. 40. 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. 41. Subject's unwillingness or inability to follow the procedures outlined in the protocol. 42. Employees or relatives of the Sponsor, Contract Research Organization, or the study center personnel.

For a full list of inclusion/exclusion criteria, please visit ClinicalTrials.gov

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