Clinical trial: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Evaluation of RPH-104 Administered at Different Doses to Patients With Acute Gout Attack (NCT04067492)

Eligibility criteria:
Inclusion Criteria:

          -  1. The subject has given his / her informed consent to participate in this study; the
             Informed Consent Form has been signed both by the patient and the Investigator;

          -  2. Established diagnosis of gout according to Gout Classification Criteria established
             by the American College of Rheumatology (ACR) and European League against Rheumatism
             (EULAR) in 2015;

          -  3. Pain in at least one joint at the screening and immediately prior to initiation of
             therapy with the study drugs, with intensity 50 mm to 100 mm according to the Visual
             Analogue Scale (VAS);

          -  4. Development of acute gout attack within 120 hours (5 days) prior to the
             randomization date;

          -  5. History of 1 or more acute gout attacks prior to the Screening Visit;

          -  6.The patients receiving uric acid-lowering drugs should continue receiving these
             drugs at a constant dose for at least 4 weeks prior to enrolment to the study and
             throughout the entire study period; the patients not receiving uric acid-lowering
             drugs may start receiving this treatment after the end of the study;

          -  7. Body mass index ≤40 kg/m2;

          -  8. QTcF interval ≤450 msec for male subjects and ≤470 msec for females on ECG at the
             screening;

          -  9. For women of child-bearing potential: negative result of the serum pregnancy test
             performed at the screening;

          -  10. The consent of a woman of child-bearing potential, as well as of a man who has
             female partners of child-bearing potential, to abstain from sexual intercourses or to
             use effective birth control methods throughout the entire study period and for 60 days
             after RPH-104 administration (if RPH-104 is administered);

          -  11. The patient is able to fulfil the requirements of the Study Protocol as judged by
             the Investigator

        Exclusion Criteria:

          -  1. The patient received therapy with ibuprofen in a dose of up to 400 mg inclusive
             within 4 hours or >400 mg within 8 hours prior to randomization.

          -  2. The patient received therapy with diclofenac in a dose of up to 50 mg inclusive
             within 8 hours or >50 mg within 24 hours prior to randomization.

          -  3. The patient received any other non-steroidal anti-inflammatory drug (NSAID) within
             24 hours prior to the randomization;

          -  4.The patient received opioids within 48 hours prior to the randomization;

          -  5. The patient received metamizole or metamizole-containing drugs within 12 hours
             prior to the randomization;

          -  6. The patient received any drug with analgesic activity (including paracetamol)
             within 6 hours prior to the randomization;

          -  7. The patient received a long-acting NSAID (half-life ≥24 hours) within 5 half-life
             periods or 1 month prior to the randomization whichever is longer;

          -  8. The patient received naproxen, meloxicam, nabumetone, celecoxib, etoricoxib or
             extended-release indomethacin within 5 days prior to the randomization;

          -  9 . The patient received corticosteroids (including their intra-articular
             administration and inhalations) within 4 weeks prior to the randomization;

          -  10. The patient received colchicine within 7 days prior to the randomization;

          -  11. Intolerance or contraindications for NSAID use;

          -  12. Contraindications for the use of Ortanol® capsules 20 mg;

          -  13. Chronic heart failure functional class II-IV (classification of NYHA);

          -  14. History of clinically significant ventricular arrhythmias or clinically
             significant atrial tachy-arrhythmias or presence of these arrhythmias at the moment of
             evaluation;

          -  15. Unstable angina or stable exercise-induced angina of functional class III or IV;

          -  16. Secondary gout, chemotherapy-induced gout, lead- or transplantation-induced gout;

          -  17. Rheumatoid arthritis, confirmed or suspected infectious septic arthritis or any
             other type of acute inflammatory arthritis;

          -  18. Clinically significant renal impairment determined based on creatinine clearance
             (estimated using the Cockcroft-Gault equation) <60 mL/min, or patients on
             hemodialysis;

          -  19. Blood coagulation disorders; history of gastrointestinal bleedings or perforation;

          -  20. Pregnant or nursing women;

          -  21. Scheduled surgical treatment or performed major surgical procedure (minor surgical
             procedures, such as catheter placement are not considered non-inclusion criteria)
             within 14 days prior to the first dose of the test drug;

          -  22. Current or suspected HIV-infection, HBsAg, Hepatitis C Virus antibodies (HCVAb),
             other acute or chronic bacterial, fungal or viral infections at the moment of
             subject's enrolment to the study;

          -  23. Presence of any risk factors for tuberculosis based on the results of assessment
             using Tuberculosis Risk Assessment Questionnaire at the screening or confirmed
             tuberculosis or any other infectious disease of the lungs or bronchi based on findings
             of the chest X-ray exam in two views performed within 3 months prior to the screening
             visit, or the need for using therapy with tuberculosis medications, such as isoniazid
             in the course of the study;

          -  24. Neutropenia, leukopenia, or thrombocytopenia determined based on the following
             laboratory parameters assessed during the screening:

               1. Absolute neutrophil count (ANC) <1.5 x 10^9/L;

               2. White blood cell count <4.0 х 10^9/L

               3. Platelet count <150 х 10^9/L;

          -  25. Immunization with live vaccines within 3 months prior to the subject's enrolment
             to the study or planned vaccination within 60 days after the expected date of the
             first dose of the test drug;

          -  26. History of allergic reactions to biologicals, Voltaren® (diclofenac) or Ortanol®
             (omeprazole);

          -  27. Contraindications for subcutaneous, intramuscular, intravenous or intra-articular
             injections;

          -  28. History of malignancy (except for patients with localized in situ basal cell
             carcinoma of the skin or in situ cervical cancer, who can be enrolled to the study
             immediately after the therapy for this disease), unless it is in remission for ≥5
             years, as well as patients who are being examined for cancer or patients with
             suspected malignancy;

          -  29. A condition or disease, which, in the Investigator's opinion, could put the
             patient's safety at risk or affect the test drug safety assessment;

          -  30. Any other conditions and diseases, such as uncontrolled diabetes mellitus,
             uncontrolled hypertension, congestive heart failure, exacerbation of peptic ulcer
             disease, clinically significant liver diseases, kidney diseases, uncontrolled thyroid
             dysfunction, unhealed wounds, ulcers or bone fractures, psychiatric disorders,
             uncontrolled epilepsy, drug dependence, which could prevent the patient from complying
             with the requirements of this Study Protocol.

          -  31. The patient received biologicals or investigational medicinal products within 5
             half-life periods of these drugs or 3 month prior to the randomization whichever is
             longer;

          -  32. Blood donation or blood loss of ≥400 mL within 8 weeks prior to the randomization.

          -  33. The patient has already been randomized in this clinical study.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 80 Years

Patient description (medical language): A 39-year-old man comes to the emergency department with an acute onset of severe left toe pain.  The toe is red and exhibits swelling. The patient is not febrile, and does not remember any recent trauma. Medical history is not significant except for the similar attacks and the diagnosis of gouty arthritis. His medication history includes Allopurinol to prevent gouty attacks. His father has the same medical condition. However, his older brother who is 41 years old is healthy with no history of gouty arthritis. Physical examination shows a swollen, tender first metatarsophalangeal joint.  Aspiration of the joint showed high leukocyte count, negative Gram stain, and numerous needle-shaped crystals, which is compatible with gouty arthritis.

Patient description (patient's own words): I'm a 39-year-old man and got admitted to the ER after an unbearable pain in my left toe. My toe was red and terribly swollen. I was still standing on my feet, not febrile and I don't remember hitting my head or anything. I don't have any special medical history, but I had been diagnosed with gout before. I take Lopurin to prevent my gouty attacks. My dad had the same problem, but my 41-year-old brother is healthy and does not have gouty attacks. The doctor did a physical exam and found that the joints between my toes and the rest of my foot were swollen and tender. The doctor renewed his diagnosis of gouty arthritis.

Does the patient match the trial criteria? Contradiction