Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Evaluation of RPH-104 Administered at Different Doses to Patients With Acute Gout Attack

• Status: Unknown status
• Trial end date: 2020-01-31
• Target enrollment: 0
• Participant gender: All

Summary

The primary goal of the study is 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: R-Pharm
• Collaborators: Covance; Data Matrix Solutions; ZAO Unimed Laboratories
• Treatments: Diclofenac

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.