Not provided
Not provided
Not provided
Not provided
Not provided
In view of the continuing insufficient patient recruitment in the study due to the difficult epidemiological situation and the need for rational allocation of company resources, as well as based on the results of the interim analysis.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Covance | INDUSTRY |
| Unimed Laboratories | INDUSTRY |
| Data Matrix Solutions | OTHER |
| Center of Pharmaceutical Analytics LLC |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RPH - 104 | Drug | solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 with the test drug measured using the Visual Analogue Scale (VAS) and compared 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". |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) - Area Under the Plasma concentration-of RPH-104 Under the Subcutaneous Administration | Including area under the plasma concentration-time curve over the dosing interval (AUC0-tau) | 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) |
Inclusion Criteria:
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:
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mikhail Samsonov | R-Pharm | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Moscow City State Healthcare Institution "O.M. Filatov Municipal Clinical Hospital No. 15" of the Moscow Department of Healthcare | Moscow | 111539 | Russia |
Not provided
Enrollment was conducted at 11 clinical sites in Russian Federation. 54 subjects were screened and 47 subjects were enrolled (randomized) and treated, 44 subjects completed the study.
The Safety Population and Efficacy Population included data from all 47 randomized patients to assess safety, treatment efficacy and pharmacodynamics.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | RPH - 4 mg | RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected. |
| FG001 | RPH - 20 mg | RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 19, 2020 |
Not provided
| INDUSTRY |
| OCT LLC | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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) |
|
| Voltaren® | Drug | Enteric-coated tablets, 25 mg and 50 mg |
|
|
| 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" | Proportion of patients who assessed the response to therapy with the test drug as "Excellent" or "Good" 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 with the test drug. The patient's response to therapy was assessed in the form of frequency tables by assessment point and therapy group. The rates of the response were specified in the evaluation form as: "Excellent", "Good", "Fair", "Weak", "Poor" (where "excellent" represents the best possible response to treatment and "poor" indicates the worst treatment response). | 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 | Change in the rate of swelling of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. The rates of swelling were specified in the evaluation form as: "absence" = no swelling, "mild" = palpable swelling, "moderate" = visible swelling, "severe" = bulging outside the joint (where "severe" represented the worst possible degree of swelling and "absence" was the best outcome). | 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 | Change in the rate of tenderness of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. Tenderness degrees: "absent" = no tenderness, "mild" = tenderness when touched, "moderate" = pain and flinching, "severe" = pain, flinching and withdrawal of the limb (where "severe" represents the worst possible degree of tenderness and "absent" is the best outcome). | 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 | Change in the rate of erythema of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline.The rates of "erythema" were specified as "absence", "presence", "impossible to evaluate". | 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 Movement Restrictions in the Specified Timeframes After Initiation of Treatment | Change in the rate of movement restrictions in the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. For the assessment, the categorical scale consistent with the Form for evaluation (Investigator's Assessment) of the restriction of movements was used. The rates of movement restrictions (amplitude of movements) were specified in the evaluation form as "1 - Normal range", "2 - Slightly limited range", " 3 - Moderately limited range" ,"4 - Severely limited range" and "5 - Joint movement is impossible " (where higher score means worse outcome). | Baseline and in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug |
| Time to Achieve the 50% Decrease in Pain Intensity in the Assessed Joint Relative to the Baseline | Time to achieve the 50% decrease in pain intensity in the assessed joint relative to the baseline VAS level. 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 one of the pain intensity measurements in accordance with the schedule: 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 |
| Time to Use of the Rescue Medication | Time to use of the rescue medication was calculated as the time in hours from the date/time of administration (first dose) of the investigational product to the date/time of the first use of the rescue medication. | from the date/time of IP administration (first dose) to the date/time of the first use of the rescue medication, up to day 60 |
| Proportion of Patients Who Received a Rescue Therapy Agent | The proportion of patients who received the rescue medication within 72 hours of starting the investigational product therapy | 72 hours after the initiation of treatment with the test drug |
| Proportion of Patients Who Received a Rescue Therapy Agent | The proportion of patients who received the rescue medication over the entire treatment period | up to day 60 |
| Changes in the Health Assessment Questionnaire (HAQ) Parameters: Disability Index | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. (The result for each of the 8 categories ("Dressing and Grooming", "Arising", "Eating", "Walking", "Hygiene", "Reach", "Grip", "Activities") of the HAQ questionnaire was calculated as the maximum score of responses (on an ordinal scale from 0 (best) to 3 (worst): without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3)) to questions included in this category. If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". The sum of points for the evaluated categories was calculated and divided by the number of categories, which gives a disability index in the range of 0 to 3.) | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| Changes in the Health Assessment Questionnaire (HAQ) Parameters: Arising | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| Changes in the Health Assessment Questionnaire (HAQ) Parameters: Eating | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| Changes in the Health Assessment Questionnaire (HAQ) Parameters: Walking | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| Changes in the Health Assessment Questionnaire (HAQ) Parameters: Hygiene | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| Changes in the Health Assessment Questionnaire (HAQ) Parameters: Grip | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| Pharmacokinetics (PK) - Area Under the Active Substance Concentration- of RPH-104 Under the Subcutaneous Administration | Including Area under the active substance concentration-time curve from zero (before drug administration) to infinity (AUC0-∞) | 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 | Including Maximum concentration of the active substance (Cmax) | 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) of RPH-104 Under the Subcutaneous Administration | Including elimination constant (Kel) | 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) -Time to Reach Maximum Concentration of the Active Substance - of RPH-104 Under the Subcutaneous Administration | Including Time to reach maximum concentration of the active substance (tmax) | 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) - Terminal Half-life -of RPH-104 Under the Subcutaneous Administration | Including terminal half-life (T 1/2) | 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) |
| Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes | Change in the serum rate of high-sensitive CRP (hs-CRP) in 24, 72 hours, on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug compared to baseline | Baseline and in 24, 72 hours, on Days 5, 6, 15, 29 and 45 after the initiation of treatment with the test drug |
| Change in the Rate of Serum Amyloid Protein A in the Specified Timeframes | Change in the rate of serum amyloid protein A in 24, 72 hours and on Day 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Baseline and in 24, 72 hours and on Day 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| Change in the Serum Rates of Cytokines: IL-1α | Change in the serum rates of IL-1α in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| Change in the Serum Rates of Cytokines: IL-1β | Change in the serum rates of IL-1β in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| Change in the Serum Rates of Cytokines: Interleukin -1 Receptor Antagonist (IL-1RA) | Change in the serum rates of IL-1RA in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| Change in the Serum Rates of Cytokines: IL-6 | Change in the serum rates of IL-6 in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| Change in the Serum Rates of Cytokines: IL-8 | Change in the serum rates of IL-8 in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| Change in the Serum Rates of Cytokines: Tumor Necrosis Factor (TNF-α) | Change in the serum rates of TNF-α in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| 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 |
| 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 |
| State Budgetary Healthcare Institution of Moscow City "Municipal Clinical Hospital No.52" of Moscow Department of Healthcare | Moscow | 123182 | Russia |
| State Budgetary Institution of Healthcare of Nizhny Novgorod region "City Clinical hospital #13 of Avozavodskiy district" | Nizhny Novgorod | 603018 | Russia |
| Federal State Budgetary Education Institution of Higher Education "Orenburg State Medical University" under Ministry of Healthcare of Russian Federation | Orenburg | 460000 | Russia |
| St. Petersburg State Budgetary Healthcare Institution "Clinical Rheumatological Hospital No.25" | Saint Petersburg | 190068 | Russia |
| State Budget Institution "Saint Petersburg Research Insitute of emergency care named after I.I. Dzhanelidze | Saint Petersburg | 192242 | Russia |
| Limited Liability company "Scientific Research Center Eco-safety" | Saint Petersburg | 196143 | Russia |
| State Insitution of healthcare "Tula regional clinical dermatovenerologic dispensary" | Tula | 300053 | Russia |
| State Autonomous Healthcare Institution of the Yaroslavl Region "N.V. Solovyev Clinical Emergency Hospital" | Yaroslavl | 150003 | Russia |
| FG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| FG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| FG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| FG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | RPH - 4 mg | RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected. |
| BG001 | RPH - 20 mg | RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected. |
| BG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| BG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| BG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| BG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Disease duration | Mean | Full Range | years |
| |||||||||||||||
| Exact number of affected joints | Mean | Full Range | number (of joints) |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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". | The baseline observation carried forward method (BOCF) was used to impute missing data for the main efficacy analysis. Missing patient data were replaced with baseline values from the time of patient discontinuation or use of the rescue medication. | Posted | Least Squares Mean | 95% Confidence Interval | mm (VAS scale) | Baseline and Day 4 (72 hours after the initiation of treatment with the test drug) |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | 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 with the test drug measured using the Visual Analogue Scale (VAS) and compared 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". | The baseline observation carried forward method (BOCF) was used to impute missing data for the main efficacy analysis. Missing patient data were replaced with baseline values from the time of patient discontinuation or use of the rescue medication. | Posted | Least Squares Mean | 95% Confidence Interval | mm (VAS scale) | 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" | Proportion of patients who assessed the response to therapy with the test drug as "Excellent" or "Good" 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 with the test drug. The patient's response to therapy was assessed in the form of frequency tables by assessment point and therapy group. The rates of the response were specified in the evaluation form as: "Excellent", "Good", "Fair", "Weak", "Poor" (where "excellent" represents the best possible response to treatment and "poor" indicates the worst treatment response). | The table shows the frequencies and proportions (%) of the number of valid observations. Values after the use of rescue medication and after withdrawal were imputed as failure. | Posted | Count of Participants | Participants | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug | Change in the rate of swelling of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. The rates of swelling were specified in the evaluation form as: "absence" = no swelling, "mild" = palpable swelling, "moderate" = visible swelling, "severe" = bulging outside the joint (where "severe" represented the worst possible degree of swelling and "absence" was the best outcome). | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics, therefore, the number of patients with analyzable data in treatment groups decreased over time. | Posted | Count of Participants | Participants | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug | Change in the rate of tenderness of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. Tenderness degrees: "absent" = no tenderness, "mild" = tenderness when touched, "moderate" = pain and flinching, "severe" = pain, flinching and withdrawal of the limb (where "severe" represents the worst possible degree of tenderness and "absent" is the best outcome). | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics, therefore, the number of patients with analyzable data in treatment groups decreased over time. | Posted | Count of Participants | Participants | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug | Change in the rate of erythema of the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline.The rates of "erythema" were specified as "absence", "presence", "impossible to evaluate". | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics, therefore, the number of patients with analyzable data in treatment groups decreased over time. | Posted | Count of Participants | Participants | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment | Change in the rate of movement restrictions in the assessed joint evaluated in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug compared to baseline. For the assessment, the categorical scale consistent with the Form for evaluation (Investigator's Assessment) of the restriction of movements was used. The rates of movement restrictions (amplitude of movements) were specified in the evaluation form as "1 - Normal range", "2 - Slightly limited range", " 3 - Moderately limited range" ,"4 - Severely limited range" and "5 - Joint movement is impossible " (where higher score means worse outcome). | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics, therefore, the number of patients with analyzable data in treatment groups decreased over time. | Posted | Count of Participants | Participants | Baseline and in 24, 48, 72 hours, on Days 5, 6, 10, 15, 18, 22, 29 and 45 following the initiation of treatment with the test drug |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Achieve the 50% Decrease in Pain Intensity in the Assessed Joint Relative to the Baseline | Time to achieve the 50% decrease in pain intensity in the assessed joint relative to the baseline VAS level. 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". | Posted | Median | 95% Confidence Interval | hours | Baseline and one of the pain intensity measurements in accordance with the schedule: 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Use of the Rescue Medication | Time to use of the rescue medication was calculated as the time in hours from the date/time of administration (first dose) of the investigational product to the date/time of the first use of the rescue medication. | Patient 01003 was excluded from the analysis of the endpoint due to the use of prohibited therapy (methylprednisolone 125 mg, IV, daily from the 2nd day of therapy until the end of the study). | Posted | Median | 95% Confidence Interval | hours | from the date/time of IP administration (first dose) to the date/time of the first use of the rescue medication, up to day 60 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Patients Who Received a Rescue Therapy Agent | The proportion of patients who received the rescue medication within 72 hours of starting the investigational product therapy | Patient 01003 was excluded from the analysis of the endpoint due to the use of prohibited therapy (methylprednisolone 125 mg, IV, daily from the 2nd day of therapy until the end of the study). | Posted | Count of Participants | Participants | 72 hours after the initiation of treatment with the test drug |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Patients Who Received a Rescue Therapy Agent | The proportion of patients who received the rescue medication over the entire treatment period | Patient 01003 was excluded from the analysis of the endpoint due to the use of prohibited therapy (methylprednisolone 125 mg, IV, daily from the 2nd day of therapy until the end of the study). | Posted | Count of Participants | Participants | up to day 60 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in the Health Assessment Questionnaire (HAQ) Parameters: Disability Index | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. (The result for each of the 8 categories ("Dressing and Grooming", "Arising", "Eating", "Walking", "Hygiene", "Reach", "Grip", "Activities") of the HAQ questionnaire was calculated as the maximum score of responses (on an ordinal scale from 0 (best) to 3 (worst): without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3)) to questions included in this category. If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". The sum of points for the evaluated categories was calculated and divided by the number of categories, which gives a disability index in the range of 0 to 3.) | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics. | Posted | Mean | Standard Deviation | units of the HAQ index | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Pharmacokinetics (PK) - Area Under the Plasma concentration-of RPH-104 Under the Subcutaneous Administration | Including area under the plasma concentration-time curve over the dosing interval (AUC0-tau) | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Pharmacokinetics (PK) - Area Under the Active Substance Concentration- of RPH-104 Under the Subcutaneous Administration | Including Area under the active substance concentration-time curve from zero (before drug administration) to infinity (AUC0-∞) | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Pharmacokinetics (PK) - Maximum Concentration of the Active Substance -of RPH-104 Under the Subcutaneous Administration | Including Maximum concentration of the active substance (Cmax) | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Pharmacokinetics (PK) of RPH-104 Under the Subcutaneous Administration | Including elimination constant (Kel) | Posted | Mean | Standard Deviation | 1/h | 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) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Pharmacokinetics (PK) -Time to Reach Maximum Concentration of the Active Substance - of RPH-104 Under the Subcutaneous Administration | Including Time to reach maximum concentration of the active substance (tmax) | Posted | Median | Full Range | hours | 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) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Pharmacokinetics (PK) - Terminal Half-life -of RPH-104 Under the Subcutaneous Administration | Including terminal half-life (T 1/2) | Posted | Median | Full Range | hours | 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) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes | Change in the serum rate of high-sensitive CRP (hs-CRP) in 24, 72 hours, on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug compared to baseline | Number of valid observations is presented. | Posted | Mean | Standard Deviation | mg/L | Baseline and in 24, 72 hours, on Days 5, 6, 15, 29 and 45 after the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Rate of Serum Amyloid Protein A in the Specified Timeframes | Change in the rate of serum amyloid protein A in 24, 72 hours and on Day 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Number of valid observations is presented. | Posted | Mean | Standard Deviation | ng/mL | Baseline and in 24, 72 hours and on Day 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Serum Rates of Cytokines: IL-1α | Change in the serum rates of IL-1α in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Number of valid observations is presented. (IL-1a values <1.10 were replaced with 1.09 for graphical representation and statistical analysis.) | Posted | Mean | Standard Deviation | pg/mL | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Serum Rates of Cytokines: IL-1β | Change in the serum rates of IL-1β in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Number of valid observations is presented. (IL-1β <0.30 values were replaced with 0.29, IL-1β > 500.00 values were replaced with 500.01 for graphical presentation and statistical analysis.) | Posted | Mean | Standard Deviation | pg/mL | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Serum Rates of Cytokines: Interleukin -1 Receptor Antagonist (IL-1RA) | Change in the serum rates of IL-1RA in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Number of valid observations is presented. (IL-1RA values <30.00 were replaced with 29.99 for graphical representation and statistical analysis.) | Posted | Mean | Standard Deviation | pg/mL | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Serum Rates of Cytokines: IL-6 | Change in the serum rates of IL-6 in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Number of valid observations is presented. (IL-6 values <0.92 were replaced with 0.913, IL-6 values >200.00 were replaced with 200.01 for graphical representation and statistical analysis.) | Posted | Mean | Standard Deviation | pg/mL | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Serum Rates of Cytokines: IL-8 | Change in the serum rates of IL-8 in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Number of valid observations is presented. (IL-8 values <2.00 were replaced with 1.99 for graphical representation and statistical analysis.) | Posted | Mean | Standard Deviation | pg/mL | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change in the Serum Rates of Cytokines: Tumor Necrosis Factor (TNF-α) | Change in the serum rates of TNF-α in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug as compared to baseline | Number of valid observations is presented. (TNF-α values <2.30 were replaced with 2.29 for graphical representation and statistical analysis.) | Posted | Mean | Standard Deviation | pg/mL | Baseline and in 24, 72 hours and on Days 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in the Health Assessment Questionnaire (HAQ) Parameters: Arising | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics. | Posted | Mean | Standard Deviation | units of the HAQ index | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in the Health Assessment Questionnaire (HAQ) Parameters: Eating | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics. | Posted | Mean | Standard Deviation | units of the HAQ index | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in the Health Assessment Questionnaire (HAQ) Parameters: Walking | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics. | Posted | Mean | Standard Deviation | units of the HAQ index | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in the Health Assessment Questionnaire (HAQ) Parameters: Hygiene | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics. | Posted | Mean | Standard Deviation | units of the HAQ index | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Changes in the Health Assessment Questionnaire (HAQ) Parameters: Grip | Changes in the Health Assessment Questionnaire (HAQ) parameters in 15, 29 and 45 days following the initiation of treatment with the test drug as compared to baseline. The result was calculated as the maximum score of responses (on an ordinal scale from 0 to 3) to questions included in this category. Patients were asked about their ability to complete these tasks in the past week using the following categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 (best) to 3 (worst). If the patient required outside help or any of the specified aids or devices to perform actions related to a certain category, then this category was assigned "2" points, if the point was not equal to "3", i.e. points "0" and "1" increased to "2". | It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics. | Posted | Mean | Standard Deviation | units of the HAQ index | Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug |
|
The safety of the investigational product was assessed over a 60-day period of therapy and follow-up. The tables show AEs that developed from the start of therapy.
The safety population included all subjects who received at least one dose of the investigational product. This population was used for all treatment safety assessments. The safety analysis of data was performed based on the actual treatment received by the patients.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | RPH - 4 mg | RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected. | 0 | 15 | 0 | 15 | 11 | 15 |
| EG001 | RPH - 20 mg | RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. | 0 | 6 | 2 | 6 | 3 | 6 |
| EG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site | 0 | 5 | 0 | 5 | 4 | 5 |
| EG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) | 0 | 9 | 1 | 9 | 2 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| drug-induced liver injury | Hepatobiliary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Mycobacterium tuberculosis complex test positive | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Diverticulum intestinal | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gastric disorder | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gastrointestinal scarring | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pancreatitis chronic | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Administration site haemorrhage | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Injection site pruritus | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Cholecystitis chronic | Hepatobiliary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Genitourinary chlamydia infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Mycoplasma infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Ureaplasma infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Bilirubin conjugated increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Lymphocyte count increased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Mycobacterium tuberculosis complex test positive | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Neutrophil percentage decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Gouty arthritis | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Joint swelling | Investigations | MedDRA 22.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Daydreaming | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Micturition disorder | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Balanoposthitis | Reproductive system and breast disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
|
Any study related information could be made public available only after Sponsors written permission.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| D.V. Bukhanova, Medical Adviser | R-Pharm | 0074959567 | 3838 | bukhanova@rpharm.ru |
| Mar 1, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D033461 | Hyperuricemia |
| D015210 | Arthritis, Gouty |
| D006073 | Gout |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D000070657 | Crystal Arthropathies |
| D012216 | Rheumatic Diseases |
| D011686 | Purine-Pyrimidine Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D004008 | Diclofenac |
| ID | Term |
|---|---|
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Male |
|
| other |
|
| Other |
The study was planned to randomize 85 patients: 15 patients in the RPH-104 4 mg group, and 14 patients in the RPH-104 20 mg, 40 mg, 80 mg and 160 mg groups each, a total of 14 patients in the Voltaren® (diclofenac) group. The sample size was calculated assuming a standard deviation of 26 mm for change in pain intensity at 72 hours. |
| It was assumed that the sample size would allow constructing a 95% CI around the mean change in pain intensity at 72 hours after the start of the investigational product use in each group with an accuracy of 30 mm change in pain intensity and would reveal statistically significant differences between the groups in pairwise comparisons, without control for type I error for multiple comparisons, taking into account the type I error α = 5%, if the difference between the compared groups is ≥ 20 mm. | ANCOVA | 0.1331 | p-value, group | Mean Difference (Final Values) | -2.05 | 2-Sided | 95 | -30.60 | 26.50 | Adjusted mean difference. Comparison with the control group [RPH-104 - Diclofenac]. | Other | The study was planned to randomize 85 patients: 15 patients in the RPH-104 4 mg group, and 14 patients in the RPH-104 20 mg, 40 mg, 80 mg and 160 mg groups each, a total of 14 patients in the Voltaren® (diclofenac) group. The sample size was calculated assuming a standard deviation of 26 mm for change in pain intensity at 72 hours. |
| It was assumed that the sample size would allow constructing a 95% CI around the mean change in pain intensity at 72 hours after the start of the investigational product use in each group with an accuracy of 30 mm change in pain intensity and would reveal statistically significant differences between the groups in pairwise comparisons, without control for type I error for multiple comparisons, taking into account the type I error α = 5%, if the difference between the compared groups is ≥ 20 mm. | ANCOVA | 0.1331 | p-value, group | Mean Difference (Final Values) | 16.70 | 2-Sided | 95 | -12.67 | 46.08 | Adjusted mean difference. Comparison with the control group [RPH-104 - Diclofenac]. | Other | The study was planned to randomize 85 patients: 15 patients in the RPH-104 4 mg group, and 14 patients in the RPH-104 20 mg, 40 mg, 80 mg and 160 mg groups each, a total of 14 patients in the Voltaren® (diclofenac) group. The sample size was calculated assuming a standard deviation of 26 mm for change in pain intensity at 72 hours. |
| It was assumed that the sample size would allow constructing a 95% CI around the mean change in pain intensity at 72 hours after the start of the investigational product use in each group with an accuracy of 30 mm change in pain intensity and would reveal statistically significant differences between the groups in pairwise comparisons, without control for type I error for multiple comparisons, taking into account the type I error α = 5%, if the difference between the compared groups is ≥ 20 mm. | ANCOVA | 0.1331 | p-value, group | Mean Difference (Final Values) | 3.12 | 2-Sided | 95 | -25.10 | 31.33 | Adjusted mean difference. Comparison with the control group [RPH-104 - Diclofenac] | Other | The study was planned to randomize 85 patients: 15 patients in the RPH-104 4 mg group, and 14 patients in the RPH-104 20 mg, 40 mg, 80 mg and 160 mg groups each, a total of 14 patients in the Voltaren® (diclofenac) group. The sample size was calculated assuming a standard deviation of 26 mm for change in pain intensity at 72 hours. |
| It was assumed that the sample size would allow constructing a 95% CI around the mean change in pain intensity at 72 hours after the start of the investigational product use in each group with an accuracy of 30 mm change in pain intensity and would reveal statistically significant differences between the groups in pairwise comparisons, without control for type I error for multiple comparisons, taking into account the type I error α = 5%, if the difference between the compared groups is ≥ 20 mm. | ANCOVA | 0.1331 | p-value, group | Mean Difference (Final Values) | 5.96 | 2-Sided | 95 | -24.22 | 36.14 | Adjusted mean difference. Comparison with the control group [RPH-104 - Diclofenac]. | Other | The study was planned to randomize 85 patients: 15 patients in the RPH-104 4 mg group, and 14 patients in the RPH-104 20 mg, 40 mg, 80 mg and 160 mg groups each, a total of 14 patients in the Voltaren® (diclofenac) group. The sample size was calculated assuming a standard deviation of 26 mm for change in pain intensity at 72 hours. |
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| RPH - 40 mg |
RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG003 |
| RPH - 80 mg |
RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
|
RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected. |
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
|
|
| RPH - 160 mg |
RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
|
|
| RPH - 160 mg |
RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
| OG002 | RPH - 40 mg | RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected. |
| OG003 | RPH - 80 mg | RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected. |
| OG004 | RPH - 160 mg | RPH-104, 160 mg, two subcutaneous injections of 80 mg administered at different injection sites. 1 vial of 2mL 40 mg/mL solution per each site |
| OG005 | Voltaren® (Diclofenac) | 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) (Voltaren®: Enteric-coated tablets, 25 mg and 50 mg) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| mild |
|
| moderate |
|
| severe |
|
|
|
|
|
|
|
|
|
|
|
|
| mild |
|
| moderate |
|
| severe |
|
|
|
|
|
|
|
|
|
|
|
|
| presence |
|
| evaluation impossible |
|
|
|
|
|
|
|
|
|
|
|
|
| 2 |
|
| 3 |
|
| 4 |
|
| 5 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|