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

The study consisted of two periods:

Period 1. In Study Period 1, eligible patients were enrolled in a group of 22 patients and randomized to receive either RPH-104 4 mg or Voltaren® (diclofenac) in the 15:7 ratio (15 RPH-104: 7 Voltaren® (diclofenac)). In order to prevent damage to the gastric and duodenal mucosa caused by Voltaren® (diclofenac), all patients receiving Voltaren® (diclofenac) had to simultaneously take Ortanol® (omeprazole) 20 mg, orally (1 capsule) daily before breakfast throughout the course of Voltaren® (diclofenac) treatment

Period 2. Upon completion of the enrollment of 22 patients, Study Period 2 started. In Period 2, newly enrolled patients were randomly assigned to one of 5 treatment groups: RPH-104 20 mg, 40 mg, 80 mg and 160 mg and active control (Voltaren® (diclofenac)). It was planned to include 14 patients in the RPH-104 groups in Period 2, and 7 patients in the Voltaren® (diclofenac) group.

The enrollment of patients in Period 1 and Period 2 was sequential. There was no pause between the enrollment of patients in Period 1 and Period 2. The study design included screening (24 hours), 11 visits to the study site, and a phone call at the end of the 60-day follow-up period.

Total number of patients which were planned to be enrolled for the study: 85 (15 patients in the group of treatment with RPH-104 4 mg and 14 patients in the each of the other treatment groups). Due to the low patient recruitment rate in the study and the negative impact of the COVID-19 pandemic on the recruitment, at the decision of the sponsor, an interim analysis of the data of 47 patients included in the study as of November 2020 was carried out in order to assess the feasibility of continuing recruitment and further conducting the study.

Patients who did not tolerate pain were allowed to receive a rescue medication, triamcinolone acetonide 40 mg intramuscularly, to intensify therapy 2 hours after the test product was administered. If the attack recurred after the use of the rescue medication, treatment was carried out in accordance with the standard practice of the hospital.

The primary efficacy endpoints were evaluated 72 hours after the end of administration of the test drug. The secondary efficacy endpoints were evaluated for 45 days of the treatment period and follow-up. The safety parameters were evaluated for 60 days of the treatment period and follow-up. Total duration of the study for a volunteer was not more than 70 days.