Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Evaluation of RPH-104 Administered at Different Doses to Patients With Acute Gout Attack
Condition: Gout Attack
MeSH terms: Gout; Arthritis, Gouty
Intervention: RPH - 104; Voltaren®
Intervention description: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial; Enteric-coated tablets, 25 mg and 50 mg
Intervention MeSH terms: Diclofenac
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: hyperuricemia; acute arthritis; gouty arthritis; gout

Summary:

      The primary goal of the study was to evaluate the parameters of efficacy, pharmacokinetics,
      pharmacodynamics, safety and tolerability of a single dose of RPH-104 in adult patients with
      acute gout attack.
    

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 the patient received RPH-104);

          -  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 extended-release naproxen, meloxicam, nabumetone, celecoxib,
             etoricoxib or 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. A history of or current clinically significant ventricular arrhythmias or
             clinically significant atrial tachyarrhythmias;

          -  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 breast-feeding women;

          -  21. Elective surgery or major surgical intervention (minor surgical procedures, such
             as catheter placement or bone marrow biopsy, are not exclusion criteria) within 14
             days before the first dose of the investigational medicinal product;

          -  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 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 was already randomized in this clinical study.