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

NCT04067492 | Terminated Phase 2 Results

• 1 other identifier: CL04018054
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Gout Attack

Keywords

hyperuricemia; acute arthritis; gouty arthritis; gout

Outcome Measures

Primary Outcomes (1)

• Change in Pain Intensity in the Assessed Joint 72 Hours After the Initiation of Treatment in Comparison to Baseline

  Change in pain intensity in the assessed joint 72 hours after the initiation of treatment with the test drug measured using the Visual Analogue Scale (VAS) in comparison to baseline. VAS is a hard copy 100 mm scale with the indications: "Absence of pain" on the left side of the scale (0 mm point) and "The most severe pain ever experienced" on the right side of the scale (100 mm point)) The better outcome would be "Absence of pain", the worse outcome would be "The most severe pain ever experienced".

  Baseline and Day 4 (72 hours after the initiation of treatment with the test drug)

Secondary Outcomes (16)

• Change in Pain Intensity in the Assessed Joint in 15, 30, 45 Minutes, 1, 1.5, 2, 4, 8, 24, 48, 72 Hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 Following the Initiation of Treatment and Compared to Baseline

  Baseline and 15, 30, 45 minutes, 1, 1.5, 2, 4, 8, 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 after the initiation of treatment

• Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good"

  15, 30, 45 minutes, 1, 1.5, 2, 4, 8, 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 after the initiation of treatment with the test drug

• Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug

  Baseline and 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug

• Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug

  Baseline and 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug

• Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug

  Baseline and 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug

Other Outcomes (14)

• Pharmacokinetics (PK) - Area Under the Plasma concentration-of RPH-104 Under the Subcutaneous Administration

  Baseline and in 2,8,24,48,72 hours,on Days 5,6,10,15,18,22,29,45 following the initiation of treatment with the test drug and on the follow-up visit (in case of premature withdrawal of patient)

• Pharmacokinetics (PK) - Area Under the Active Substance Concentration- of RPH-104 Under the Subcutaneous Administration

  Baseline and in 2,8,24,48,72 hours,on Days 5,6,10,15,18,22,29,45 following the initiation of treatment with the test drug and on the follow-up visit (in case of premature withdrawal of patient)

• Pharmacokinetics (PK) - Maximum Concentration of the Active Substance -of RPH-104 Under the Subcutaneous Administration

  Baseline and in 2,8,24,48,72 hours,on Days 5,6,10,15,18,22,29,45 following the initiation of treatment with the test drug and on the follow-up visit (in case of premature withdrawal of patient)

Study Arms (6)

RPH - 4 mg

EXPERIMENTAL

Subjects randomized to receive RPH-104, 4 mg, subcutaneous single-dose injection. In order to administer RPH-104 at the dose of 4 mg, 0.1 mL of RPH-104 solution is injected.

Drug: RPH - 104

RPH - 20 mg

EXPERIMENTAL

Subjects randomized to receive RPH-104, 20 mg, subcutaneous single-dose injection. In order to administer RPH-104 at the dose of 20 mg, 0.5 mL of RPH-104 solution is injected.

Drug: RPH - 104

RPH - 40 mg

EXPERIMENTAL

Subjects randomized to receive RPH-104, 40 mg, subcutaneous single-dose injection. In order to administer RPH-104 at the dose of 40 mg, 1 mL of RPH-104 solution is injected.

Drug: RPH - 104

RPH - 80 mg

EXPERIMENTAL

Subjects randomized to receive RPH-104, 80 mg, subcutaneous single-dose injection. In order to administer RPH-104 at the dose of 80 mg, 2 mL (whole vial) of RPH-104 solution is injected.

Drug: RPH - 104

RPH - 160 mg

EXPERIMENTAL

Subjects randomized to receive RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. (1 vial of 2mL solution per each site)

Drug: RPH - 104

Voltaren® (diclofenac)

ACTIVE COMPARATOR

Subjects randomized to receive Voltaren® (diclofenac) orally with water at the dose 50 mg thrice daily for 3 days (150 mg total daily dose), then 25 mg thrice daily for 9 days (75 mg total daily dose)

Drug: Voltaren®

Interventions

RPH - 104 DRUG

solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial

RPH - 160 mg; RPH - 20 mg; RPH - 4 mg; RPH - 40 mg; RPH - 80 mg

Voltaren® DRUG

Enteric-coated tablets, 25 mg and 50 mg

Also known as: Diclofenac

Voltaren® (diclofenac)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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;
• \. 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;
• \. 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);
• \. Development of acute gout attack within 120 hours (5 days) prior to the randomization date;
• \. History of 1 or more acute gout attacks prior to the Screening Visit;
• 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;
• \. Body mass index ≤40 kg/m2;
• \. QTcF interval ≤450 msec for male subjects and ≤470 msec for females on ECG at the screening;
• \. For women of child-bearing potential: negative result of the serum pregnancy test performed at the screening;
• \. 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);
• \. The patient is able to fulfil the requirements of the Study Protocol as judged by the Investigator

You may not qualify if:

• \. 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.
• \. 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.
• \. The patient received any other non-steroidal anti-inflammatory drug (NSAID) within 24 hours prior to the randomization;
• The patient received opioids within 48 hours prior to the randomization;
• \. The patient received metamizole or metamizole-containing drugs within 12 hours prior to the randomization;
• \. The patient received any drug with analgesic activity (including paracetamol) within 6 hours prior to the randomization;
• \. 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;
• \. The patient received extended-release naproxen, meloxicam, nabumetone, celecoxib, etoricoxib or indomethacin within 5 days prior to the randomization;
• The patient received corticosteroids (including their intra-articular administration and inhalations) within 4 weeks prior to the randomization;
• \. The patient received colchicine within 7 days prior to the randomization;
• \. Intolerance or contraindications for NSAID use;
• \. Contraindications for the use of Ortanol® capsules 20 mg;
• \. Chronic heart failure functional class II-IV (classification of NYHA);
• \. A history of or current clinically significant ventricular arrhythmias or clinically significant atrial tachyarrhythmias;
• \. Unstable angina or stable exercise-induced angina of functional class III or IV;

Sponsors & Collaborators

• R-Pharm: lead
• Covance: collaborator
• Unimed Laboratories: collaborator
• Data Matrix Solutions: collaborator
• Center of Pharmaceutical Analytics LLC: collaborator
• OCT LLC: collaborator

Study Sites (11)

Moscow City State Healthcare Institution "O.M. Filatov Municipal Clinical Hospital No. 15" of the Moscow Department of Healthcare

Moscow, 111539, Russia

Location

State Budgetary Healthcare Institution of Moscow City "Municipal Clinical Hospital No.1 named after N.I. Pirogov" of Moscow Department of Healthcare

Moscow, 119049, Russia

Location

Federal State Autonomous Educational Institution of Higher Education "I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Moscow, 119991, Russia

Location

State Budgetary Healthcare Institution of Moscow City "Municipal Clinical Hospital No.52" of Moscow Department of Healthcare

Moscow, 123182, Russia

Location

State Budgetary Institution of Healthcare of Nizhny Novgorod region "City Clinical hospital #13 of Avozavodskiy district"

Nizhny Novgorod, 603018, Russia

Location

Federal State Budgetary Education Institution of Higher Education "Orenburg State Medical University" under Ministry of Healthcare of Russian Federation

Orenburg, 460000, Russia

Location

St. Petersburg State Budgetary Healthcare Institution "Clinical Rheumatological Hospital No.25"

Saint Petersburg, 190068, Russia

Location

State Budget Institution "Saint Petersburg Research Insitute of emergency care named after I.I. Dzhanelidze

Saint Petersburg, 192242, Russia

Location

Limited Liability company "Scientific Research Center Eco-safety"

Saint Petersburg, 196143, Russia

Location

State Insitution of healthcare "Tula regional clinical dermatovenerologic dispensary"

Tula, 300053, Russia

Location

State Autonomous Healthcare Institution of the Yaroslavl Region "N.V. Solovyev Clinical Emergency Hospital"

Yaroslavl, 150003, Russia

Location

MeSH Terms

Conditions

Hyperuricemia; Arthritis, Gouty; Gout

Interventions

Diclofenac

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: D.V. Bukhanova, Medical Adviser
• Organization: R-Pharm

bukhanova@rpharm.ru

0074959567

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 26, 2019
• Study Start: March 26, 2018
• Primary Completion: March 16, 2020
• Study Completion: May 12, 2020
• Last Updated: July 25, 2022
• Results First Posted: July 25, 2022

Record last verified: 2022-03

Locations

RU (11)