Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Evaluation of RPH-104 Administered at Different Doses to Patients With Acute Gout Attack (NCT NCT04067492)

Last Updated: 2022-07-25

Results Overview

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".

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

47 participants

Primary outcome timeframe

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

Results posted on

2022-07-25

Participant Flow

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.

Participant milestones

Participant milestones
Measure	RPH - 4 mg RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 80 mg RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	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	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)
Overall Study STARTED	15	6	6	6	5	9
Overall Study COMPLETED	15	5	6	5	5	8
Overall Study NOT COMPLETED	0	1	0	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	RPH - 20 mg RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 80 mg RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	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)
Overall Study Lost to Follow-up	0	0	1
Overall Study closure of city borders because of COVID-19 quarantine	1	0	0
Overall Study COVID-19 epidemiological situation	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RPH - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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)	Total n=47 Participants Total of all reporting groups
Age, Continuous	52.3 years n=5 Participants	51.7 years n=7 Participants	42.8 years n=5 Participants	56.5 years n=4 Participants	53.6 years n=21 Participants	52.2 years n=10 Participants	51.5 years n=115 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants	3 Participants n=115 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	7 Participants n=10 Participants	44 Participants n=115 Participants
Race/Ethnicity, Customized Race · Caucasian/White	15 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	9 Participants n=10 Participants	47 Participants n=115 Participants
Race/Ethnicity, Customized Race · other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Disease duration	8.13 years n=5 Participants	7.65 years n=7 Participants	8.04 years n=5 Participants	9.16 years n=4 Participants	13.55 years n=21 Participants	6.41 years n=10 Participants	8.82 years n=115 Participants
Exact number of affected joints	5.3 number (of joints) n=5 Participants	3.0 number (of joints) n=7 Participants	5.7 number (of joints) n=5 Participants	2.7 number (of joints) n=4 Participants	6.2 number (of joints) n=21 Participants	3.0 number (of joints) n=10 Participants	4.32 number (of joints) n=115 Participants

PRIMARY outcome

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

Population: 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.

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Change in Pain Intensity in the Assessed Joint 72 Hours After the Initiation of Treatment in Comparison to Baseline	-33.39 mm (VAS scale) Interval -55.53 to -11.24	-30.55 mm (VAS scale) Interval -54.46 to -6.64	-36.51 mm (VAS scale) Interval -55.11 to -17.9	-7.88 mm (VAS scale) Interval -22.26 to 6.5	-38.56 mm (VAS scale) Interval -60.39 to -16.72	-19.80 mm (VAS scale) Interval -41.83 to 2.22

SECONDARY outcome

Timeframe: 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

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".

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
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 Day 1/ 2 hours	-13.86 mm (VAS scale) Interval -32.15 to 4.44	-19.59 mm (VAS scale) Interval -39.62 to 0.44	-20.56 mm (VAS scale) Interval -35.52 to -5.6	-22.07 mm (VAS scale) Interval -33.65 to -10.48	-25.14 mm (VAS scale) Interval -43.42 to -6.86	-24.63 mm (VAS scale) Interval -42.92 to -6.34
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 Day 1/15 minutes	-1.52 mm (VAS scale) Interval -8.39 to 5.34	-5.75 mm (VAS scale) Interval -13.23 to 1.74	-3.78 mm (VAS scale) Interval -9.44 to 1.88	-2.00 mm (VAS scale) Interval -6.38 to 2.38	-6.97 mm (VAS scale) Interval -13.81 to -0.14	-5.91 mm (VAS scale) Interval -12.76 to 0.94
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 Day 1/ 1.5 hours	-14.69 mm (VAS scale) Interval -31.26 to 1.88	-17.79 mm (VAS scale) Interval -35.92 to 0.35	-13.67 mm (VAS scale) Interval -27.22 to -0.12	-22.47 mm (VAS scale) Interval -32.96 to -11.97	-15.14 mm (VAS scale) Interval -31.7 to 1.42	-21.26 mm (VAS scale) Interval -37.82 to -4.7
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 Day 4	-34.52 mm (VAS scale) Interval -56.19 to -12.85	-30.75 mm (VAS scale) Interval -54.47 to -7.02	-38.12 mm (VAS scale) Interval -55.83 to -20.4	-6.67 mm (VAS scale) Interval -20.38 to 7.05	-38.77 mm (VAS scale) Interval -60.43 to -17.11	-18.91 mm (VAS scale) Interval -40.58 to 2.76
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 Day 6	-22.86 mm (VAS scale) Interval -44.38 to -1.33	-29.15 mm (VAS scale) Interval -52.71 to -5.58	-42.45 mm (VAS scale) Interval -60.04 to -24.86	-4.80 mm (VAS scale) Interval -18.42 to 8.82	-34.44 mm (VAS scale) Interval -55.95 to -12.93	-12.43 mm (VAS scale) Interval -33.95 to 9.09
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 Day 15	-12.69 mm (VAS scale) Interval -34.93 to 9.55	-28.95 mm (VAS scale) Interval -53.3 to -4.6	-38.34 mm (VAS scale) Interval -56.51 to -20.16	-4.13 mm (VAS scale) Interval -18.21 to 9.94	-41.77 mm (VAS scale) Interval -64.0 to -19.55	-12.41 mm (VAS scale) Interval -34.64 to 9.82
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 Day 1/ 4 hours	-14.36 mm (VAS scale) Interval -34.52 to 5.81	-20.35 mm (VAS scale) Interval -42.43 to 1.73	-22.67 mm (VAS scale) Interval -39.15 to -6.19	-21.87 mm (VAS scale) Interval -34.63 to -9.1	-27.27 mm (VAS scale) Interval -47.43 to -7.12	-21.44 mm (VAS scale) Interval -41.61 to -1.28
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 Day 1/ 8 hours	-16.52 mm (VAS scale) Interval -36.82 to 3.77	-25.35 mm (VAS scale) Interval -47.57 to -3.13	-25.67 mm (VAS scale) Interval -42.26 to -9.08	-14.20 mm (VAS scale) Interval -27.05 to -1.35	-29.61 mm (VAS scale) Interval -49.89 to -9.32	-18.93 mm (VAS scale) Interval -39.22 to 1.36
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 Day 1/30 minutes	-5.19 mm (VAS scale) Interval -15.92 to 5.54	-10.57 mm (VAS scale) Interval -22.3 to 1.16	-5.45 mm (VAS scale) Interval -14.24 to 3.35	-10.00 mm (VAS scale) Interval -16.81 to -3.19	-14.16 mm (VAS scale) Interval -24.87 to -3.45	-6.43 mm (VAS scale) Interval -17.15 to 4.29
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 Day 1/45 minutes	-9.36 mm (VAS scale) Interval -22.78 to 4.07	-11.77 mm (VAS scale) Interval -26.45 to 2.92	-8.56 mm (VAS scale) Interval -19.55 to 2.43	-16.20 mm (VAS scale) Interval -24.71 to -7.69	-16.14 mm (VAS scale) Interval -29.55 to -2.73	-7.91 mm (VAS scale) Interval -21.33 to 5.51
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 Day 1/ 1 hour	-12.52 mm (VAS scale) Interval -29.03 to 3.99	-15.99 mm (VAS scale) Interval -34.06 to 2.09	-12.67 mm (VAS scale) Interval -26.17 to 0.83	-19.67 mm (VAS scale) Interval -30.12 to -9.21	-15.81 mm (VAS scale) Interval -32.3 to 0.69	-11.76 mm (VAS scale) Interval -28.27 to 4.74
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 Day 2	-25.52 mm (VAS scale) Interval -45.53 to -5.52	-30.35 mm (VAS scale) Interval -52.25 to -8.44	-30.34 mm (VAS scale) Interval -46.69 to -13.98	-10.60 mm (VAS scale) Interval -23.27 to 2.07	-37.77 mm (VAS scale) Interval -57.77 to -17.78	-20.94 mm (VAS scale) Interval -40.95 to -0.94
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 Day 3	-34.69 mm (VAS scale) Interval -55.03 to -14.35	-30.15 mm (VAS scale) Interval -52.41 to -7.88	-38.67 mm (VAS scale) Interval -55.29 to -22.05	-3.33 mm (VAS scale) Interval -16.21 to 9.54	-35.77 mm (VAS scale) Interval -56.1 to -15.45	-27.94 mm (VAS scale) Interval -48.28 to -7.61
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 Day 5	-35.86 mm (VAS scale) Interval -57.79 to -13.92	-31.35 mm (VAS scale) Interval -55.36 to -7.33	-42.78 mm (VAS scale) Interval -60.71 to -24.86	-4.73 mm (VAS scale) Interval -18.62 to 9.15	-31.27 mm (VAS scale) Interval -53.2 to -9.35	-13.64 mm (VAS scale) Interval -35.57 to 8.28
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 Day 10	-23.52 mm (VAS scale) Interval -46.52 to -0.53	-29.15 mm (VAS scale) Interval -54.33 to -3.96	-37.78 mm (VAS scale) Interval -56.57 to -18.99	-6.73 mm (VAS scale) Interval -21.29 to 7.82	-37.27 mm (VAS scale) Interval -60.26 to -14.29	-12.43 mm (VAS scale) Interval -35.42 to 10.57
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 Day 18	-12.69 mm (VAS scale) Interval -34.99 to 9.61	-29.75 mm (VAS scale) Interval -54.17 to -5.33	-28.45 mm (VAS scale) Interval -46.67 to -10.22	-4.07 mm (VAS scale) Interval -18.18 to 10.05	-42.61 mm (VAS scale) Interval -64.9 to -20.31	-12.74 mm (VAS scale) Interval -35.04 to 9.55
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 Day 22	-12.69 mm (VAS scale) Interval -35.17 to 9.79	-28.35 mm (VAS scale) Interval -52.96 to -3.73	-30.34 mm (VAS scale) Interval -48.71 to -11.97	-3.20 mm (VAS scale) Interval -17.43 to 11.03	-44.61 mm (VAS scale) Interval -67.08 to -22.14	-13.58 mm (VAS scale) Interval -36.05 to 8.9
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 Day 29	-12.69 mm (VAS scale) Interval -35.28 to 9.9	-17.95 mm (VAS scale) Interval -42.68 to 6.79	-23.89 mm (VAS scale) Interval -42.35 to -5.43	-4.07 mm (VAS scale) Interval -18.36 to 10.23	-44.94 mm (VAS scale) Interval -67.52 to -22.36	-13.58 mm (VAS scale) Interval -36.16 to 9.01
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 Day 45	-12.69 mm (VAS scale) Interval -34.93 to 9.55	-19.75 mm (VAS scale) Interval -44.09 to 4.6	-23.34 mm (VAS scale) Interval -41.51 to -5.16	-2.60 mm (VAS scale) Interval -16.67 to 11.48	-46.94 mm (VAS scale) Interval -69.17 to -24.71	-13.58 mm (VAS scale) Interval -35.81 to 8.66

SECONDARY outcome

Timeframe: 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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/ 1 hour	2 Participants	0 Participants	1 Participants	3 Participants	0 Participants	0 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 2	1 Participants	2 Participants	2 Participants	1 Participants	0 Participants	2 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 45	1 Participants	1 Participants	3 Participants	0 Participants	1 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/15 minutes	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/30 minutes	1 Participants	0 Participants	2 Participants	2 Participants	1 Participants	0 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/45 minutes	2 Participants	0 Participants	2 Participants	3 Participants	1 Participants	0 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/ 1.5 hours	1 Participants	0 Participants	1 Participants	3 Participants	0 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/ 2 hours	1 Participants	0 Participants	1 Participants	3 Participants	0 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/ 4 hours	1 Participants	1 Participants	2 Participants	2 Participants	0 Participants	2 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 1/ 8 hours	1 Participants	2 Participants	4 Participants	2 Participants	1 Participants	2 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 3	1 Participants	2 Participants	5 Participants	1 Participants	1 Participants	2 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 4	3 Participants	2 Participants	6 Participants	1 Participants	1 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 5	3 Participants	2 Participants	6 Participants	1 Participants	1 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 6	2 Participants	2 Participants	6 Participants	1 Participants	2 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 10	2 Participants	2 Participants	6 Participants	1 Participants	1 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 15	1 Participants	2 Participants	6 Participants	1 Participants	2 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 18	1 Participants	2 Participants	4 Participants	1 Participants	1 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 22	1 Participants	2 Participants	5 Participants	0 Participants	2 Participants	1 Participants
Proportion of Patients Who Assessed the Response to Therapy With the Test Drug as "Excellent" or "Good" Day 29	1 Participants	1 Participants	3 Participants	1 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: 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

Population: 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.

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).

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · mild	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · absence	1 Participants	1 Participants	2 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · mild	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · absence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · mild	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · moderate	4 Participants	1 Participants	5 Participants	9 Participants	3 Participants	2 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · severe	2 Participants	4 Participants	3 Participants	5 Participants	3 Participants	4 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · absence	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · mild	1 Participants	1 Participants	5 Participants	2 Participants	2 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · moderate	3 Participants	2 Participants	3 Participants	8 Participants	3 Participants	2 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · severe	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	3 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · absence	3 Participants	1 Participants	2 Participants	1 Participants	1 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · mild	0 Participants	0 Participants	5 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · moderate	1 Participants	2 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · absence	3 Participants	1 Participants	4 Participants	1 Participants	2 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · mild	0 Participants	1 Participants	2 Participants	1 Participants	2 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · moderate	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · absence	3 Participants	1 Participants	4 Participants	1 Participants	2 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · mild	0 Participants	1 Participants	2 Participants	1 Participants	1 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · moderate	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · absence	2 Participants	1 Participants	4 Participants	1 Participants	2 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · mild	0 Participants	2 Participants	3 Participants	1 Participants	2 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · absence	2 Participants	2 Participants	4 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · mild	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · absence	1 Participants	2 Participants	6 Participants	1 Participants	4 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · mild	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · absence	1 Participants	2 Participants	2 Participants	1 Participants	2 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · mild	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · mild	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · absence	1 Participants	0 Participants	4 Participants	1 Participants	4 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · absence	1 Participants	0 Participants	4 Participants	0 Participants	3 Participants	1 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Swelling of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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 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).

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · severe	2 Participants	3 Participants	3 Participants	2 Participants	1 Participants	3 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · moderate	3 Participants	1 Participants	2 Participants	6 Participants	0 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · absence	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · mild	2 Participants	2 Participants	6 Participants	1 Participants	5 Participants	2 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · absence	2 Participants	1 Participants	3 Participants	1 Participants	2 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · mild	1 Participants	2 Participants	4 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · mild	0 Participants	1 Participants	4 Participants	1 Participants	2 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · moderate	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · mild	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · absence	1 Participants	1 Participants	3 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · mild	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · mild	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · absence	1 Participants	1 Participants	1 Participants	0 Participants	3 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · mild	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · absence	1 Participants	0 Participants	4 Participants	0 Participants	3 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · absence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · mild	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · moderate	4 Participants	2 Participants	6 Participants	12 Participants	4 Participants	3 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · absence	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · mild	1 Participants	1 Participants	6 Participants	4 Participants	5 Participants	3 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · severe	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · moderate	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · absence	3 Participants	1 Participants	3 Participants	1 Participants	2 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · absence	2 Participants	1 Participants	4 Participants	1 Participants	2 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · mild	0 Participants	2 Participants	3 Participants	1 Participants	2 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · absence	2 Participants	2 Participants	4 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · absence	1 Participants	2 Participants	5 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · mild	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · absence	1 Participants	2 Participants	1 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Tenderness of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · mild	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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 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".

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · absence	2 Participants	3 Participants	4 Participants	2 Participants	3 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · absence	1 Participants	3 Participants	2 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · presence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 18 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · absence	1 Participants	2 Participants	2 Participants	1 Participants	4 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · absence	1 Participants	1 Participants	4 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · presence	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 22 · presence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 29 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · absence	1 Participants	1 Participants	4 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · presence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug 45 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · absence	0 Participants	0 Participants	2 Participants	3 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · presence	5 Participants	5 Participants	7 Participants	12 Participants	6 Participants	6 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Baseline · evaluation impossible	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · absence	1 Participants	2 Participants	2 Participants	5 Participants	2 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · presence	4 Participants	2 Participants	6 Participants	7 Participants	3 Participants	4 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 2/ 24 hours · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · absence	3 Participants	1 Participants	5 Participants	2 Participants	4 Participants	2 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 3/ 48 hours · presence	1 Participants	2 Participants	2 Participants	0 Participants	1 Participants	2 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · absence	3 Participants	2 Participants	7 Participants	2 Participants	4 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · presence	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 4/ 72 hours · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · absence	3 Participants	3 Participants	7 Participants	2 Participants	4 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · presence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 5 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · absence	2 Participants	3 Participants	7 Participants	2 Participants	4 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · presence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 6 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · presence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 10 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · absence	1 Participants	3 Participants	6 Participants	1 Participants	4 Participants	1 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · presence	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Erythema of the Assessed Joint Evaluated After the Initiation of Treatment With the Test Drug Day 15 · evaluation impossible	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

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).

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Baseline · 3	3 Participants	2 Participants	6 Participants	5 Participants	2 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 22 · 1	1 Participants	1 Participants	2 Participants	0 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Baseline · 5	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 2/ 24 hours · 1	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 2/ 24 hours · 2	2 Participants	2 Participants	4 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 2/ 24 hours · 3	2 Participants	1 Participants	3 Participants	7 Participants	3 Participants	3 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 2/ 24 hours · 4	1 Participants	1 Participants	1 Participants	3 Participants	1 Participants	2 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 3/ 48 hours · 4	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 3/ 48 hours · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 4/ 72 hours · 1	2 Participants	1 Participants	2 Participants	1 Participants	2 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 4/ 72 hours · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 5 · 1	3 Participants	1 Participants	3 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 5 · 2	0 Participants	1 Participants	4 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 5 · 3	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 5 · 4	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 29 · 2	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 6 · 3	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 6 · 4	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 6 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 10 · 1	2 Participants	2 Participants	3 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 10 · 4	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 15 · 1	1 Participants	2 Participants	5 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 15 · 2	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 15 · 3	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 15 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 18 · 2	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 18 · 3	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 18 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 22 · 2	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 22 · 3	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 22 · 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 29 · 3	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 3/ 48 hours · 3	1 Participants	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Baseline · 1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Baseline · 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 4/ 72 hours · 2	1 Participants	1 Participants	5 Participants	0 Participants	3 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 4/ 72 hours · 3	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 4/ 72 hours · 4	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 5 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 6 · 1	2 Participants	1 Participants	5 Participants	1 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 6 · 2	0 Participants	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Baseline · 4	2 Participants	2 Participants	3 Participants	9 Participants	4 Participants	5 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 10 · 2	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 10 · 3	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 10 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 15 · 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 18 · 1	1 Participants	2 Participants	2 Participants	0 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 2/ 24 hours · 5	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 3/ 48 hours · 1	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 3/ 48 hours · 2	2 Participants	1 Participants	4 Participants	1 Participants	5 Participants	2 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 29 · 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 29 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 18 · 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 22 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 29 · 1	1 Participants	0 Participants	4 Participants	0 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 45 · 5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 45 · 1	1 Participants	0 Participants	4 Participants	0 Participants	3 Participants	1 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 45 · 2	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 45 · 3	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Change in the Rate of Movement Restrictions in the Specified Timeframes After Initiation of Treatment Day 45 · 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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 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".

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Time to Achieve the 50% Decrease in Pain Intensity in the Assessed Joint Relative to the Baseline	NA hours Interval 0.8 to No median estimate was obtained due to the small group sizes and the small number of events assessed.	8.0 hours Interval 4.0 to No CI estimate was obtained due to the small group sizes and the small number of events assessed.	47.3 hours Interval 0.8 to No CI estimate was obtained due to the small group sizes and the small number of events assessed.	NA hours Interval 0.8 to No median estimate was obtained due to the small group sizes and the small number of events assessed.	6.0 hours Interval 0.3 to No CI estimate was obtained due to the small group sizes and the small number of events assessed.	NA hours Interval 1.5 to No median estimate was obtained due to the small group sizes and the small number of events assessed.

SECONDARY outcome

Timeframe: 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

Population: 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).

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.

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=14 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Time to Use of the Rescue Medication	84.6 hours Interval 22.7 to No CI estimate was obtained due to the small group sizes and the small number of events assessed.	NA hours Interval 3.0 to No median estimate was obtained due to the small group sizes and the small number of events assessed.	NA hours Interval 4.4 to No median estimate was obtained due to the small group sizes and the small number of events assessed.	23.7 hours Interval 21.3 to 24.5	NA hours Interval 3.1 to No median estimate was obtained due to the small group sizes and the small number of events assessed.	71.8 hours Interval 24.4 to No CI estimate was obtained due to the small group sizes and the small number of events assessed.

SECONDARY outcome

Timeframe: 72 hours after the initiation of treatment with the test drug

The proportion of patients who received the rescue medication within 72 hours of starting the investigational product therapy

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=14 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Proportion of Patients Who Received a Rescue Therapy Agent	3 Participants	2 Participants	2 Participants	12 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: up to day 60

The proportion of patients who received the rescue medication over the entire treatment period

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=14 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Proportion of Patients Who Received a Rescue Therapy Agent	4 Participants	2 Participants	3 Participants	13 Participants	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug

Population: It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics.

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.)

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Disability Index Baseline value	1.1 units of the HAQ index Standard Deviation 0.649	1.6 units of the HAQ index Standard Deviation 0.615	1.32 units of the HAQ index Standard Deviation 0.577	1.3 units of the HAQ index Standard Deviation 0.802	1.23 units of the HAQ index Standard Deviation 0.578	1.75 units of the HAQ index Standard Deviation 0.806
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Disability Index Change Day 15	-0.63 units of the HAQ index Standard Deviation NA small group size	-1.06 units of the HAQ index Standard Deviation 0.619	-0.56 units of the HAQ index Standard Deviation 0.342	-0.75 units of the HAQ index Standard Deviation NA small group size	-0.63 units of the HAQ index Standard Deviation 0.685	-0.88 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Disability Index Change Day 29	-0.63 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.53	-0.38 units of the HAQ index Standard Deviation 0.144	-0.13 units of the HAQ index Standard Deviation NA small group size	-1.09 units of the HAQ index Standard Deviation 0.672	-1.25 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Disability Index Change Day 45	-0.63 units of the HAQ index Standard Deviation NA small group size	-0.56 units of the HAQ index Standard Deviation 0.619	-0.44 units of the HAQ index Standard Deviation 0.298	-0.38 units of the HAQ index Standard Deviation NA small group size	-1.42 units of the HAQ index Standard Deviation 0.382	-1.38 units of the HAQ index Standard Deviation NA small group size

SECONDARY outcome

Timeframe: Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug

Population: It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics.

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".

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Arising Baseline value	0.7 units of the HAQ index Standard Deviation 0.82	1.4 units of the HAQ index Standard Deviation 0.55	1.2 units of the HAQ index Standard Deviation 0.97	0.9 units of the HAQ index Standard Deviation 0.74	1.3 units of the HAQ index Standard Deviation 0.52	1.5 units of the HAQ index Standard Deviation 1.05
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Arising Change Day 15	0.0 units of the HAQ index Standard Deviation NA small group size	-1.0 units of the HAQ index Standard Deviation 0.00	-0.5 units of the HAQ index Standard Deviation 0.55	-1.0 units of the HAQ index Standard Deviation NA small group size	-1.0 units of the HAQ index Standard Deviation 0.82	-1.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Arising Change Day 29	0.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	0.0 units of the HAQ index Standard Deviation 0.82	-1.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 0.50	-1.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Arising Change Day 45	0.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	0.0 units of the HAQ index Standard Deviation 0.0	-1.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 0.58	-1.0 units of the HAQ index Standard Deviation NA small group size

SECONDARY outcome

Timeframe: Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug

Population: It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics.

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Eating Baseline value	0.8 units of the HAQ index Standard Deviation 1.17	1.0 units of the HAQ index Standard Deviation 1.00	0.7 units of the HAQ index Standard Deviation 1.00	1.0 units of the HAQ index Standard Deviation 1.20	0.7 units of the HAQ index Standard Deviation 0.82	1.3 units of the HAQ index Standard Deviation 1.37
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Eating Change Day 15	0.0 units of the HAQ index Standard Deviation NA small group size	0.0 units of the HAQ index Standard Deviation 0.00	-0.3 units of the HAQ index Standard Deviation 0.52	0.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 1.0	0.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Eating Change Day 29	0.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	-0.3 units of the HAQ index Standard Deviation 0.50	0.0 units of the HAQ index Standard Deviation NA small group size	-1.0 units of the HAQ index Standard Deviation 0.82	0.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Eating Change Day 45	0.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	-0.3 units of the HAQ index Standard Deviation 0.5	0.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 0.58	0.0 units of the HAQ index Standard Deviation NA small group size

SECONDARY outcome

Timeframe: Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug

Population: It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics.

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Walking Baseline value	1.3 units of the HAQ index Standard Deviation 0.82	1.6 units of the HAQ index Standard Deviation 1.14	1.8 units of the HAQ index Standard Deviation 0.67	1.4 units of the HAQ index Standard Deviation 0.74	1.8 units of the HAQ index Standard Deviation 0.75	1.8 units of the HAQ index Standard Deviation 1.17
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Walking Change Day 15	-1.0 units of the HAQ index Standard Deviation NA small group size	-1.5 units of the HAQ index Standard Deviation 0.71	-0.7 units of the HAQ index Standard Deviation 0.82	0.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 0.96	-1.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Walking Change Day 29	-1.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	-0.3 units of the HAQ index Standard Deviation 0.50	0.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 0.96	-2.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Walking Change Day 45	-1.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	-0.8 units of the HAQ index Standard Deviation 0.96	0.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 1.15	-2.0 units of the HAQ index Standard Deviation NA small group size

SECONDARY outcome

Timeframe: Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug

Population: It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics.

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Hygiene Change Day 15	-1.0 units of the HAQ index Standard Deviation NA small group size	-2.5 units of the HAQ index Standard Deviation 0.71	-0.5 units of the HAQ index Standard Deviation 0.55	-1.0 units of the HAQ index Standard Deviation NA small group size	-0.3 units of the HAQ index Standard Deviation 1.26	-1.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Hygiene Change Day 29	-1.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	-0.5 units of the HAQ index Standard Deviation 0.58	1.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 0.96	-1.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Hygiene Change Day 45	-1.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	-1.0 units of the HAQ index Standard Deviation 0.82	0.0 units of the HAQ index Standard Deviation NA small group size	-1.7 units of the HAQ index Standard Deviation 0.58	-1.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Hygiene Baseline value	1.5 units of the HAQ index Standard Deviation 1.05	2.2 units of the HAQ index Standard Deviation 0.45	1.3 units of the HAQ index Standard Deviation 0.50	1.2 units of the HAQ index Standard Deviation 1.21	1.2 units of the HAQ index Standard Deviation 0.98	1.7 units of the HAQ index Standard Deviation 1.03

SECONDARY outcome

Timeframe: Baseline and 15, 29 and 45 days following the initiation of treatment with the test drug

Population: It should be noted that estimates following the use of the rescue medication or a prohibited analgesic were not included in the descriptive statistics.

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Grip Baseline value	1.0 units of the HAQ index Standard Deviation 1.10	1.2 units of the HAQ index Standard Deviation 1.10	0.4 units of the HAQ index Standard Deviation 0.73	1.4 units of the HAQ index Standard Deviation 0.99	1.0 units of the HAQ index Standard Deviation 0.63	1.2 units of the HAQ index Standard Deviation 1.17
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Grip Change Day 15	-1.0 units of the HAQ index Standard Deviation NA small group size	0.0 units of the HAQ index Standard Deviation 0.00	-0.2 units of the HAQ index Standard Deviation 0.41	-1.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.58	0.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Grip Change Day 29	-1.0 units of the HAQ index Standard Deviation NA small group size	-0.5 units of the HAQ index Standard Deviation 0.71	-0.3 units of the HAQ index Standard Deviation 0.5	-1.0 units of the HAQ index Standard Deviation NA small group size	-1.0 units of the HAQ index Standard Deviation 0.82	0.0 units of the HAQ index Standard Deviation NA small group size
Changes in the Health Assessment Questionnaire (HAQ) Parameters: Grip Change Day 45	-1.0 units of the HAQ index Standard Deviation NA small group size	-1.0 units of the HAQ index Standard Deviation 1.41	0.3 units of the HAQ index Standard Deviation 1.26	-1.0 units of the HAQ index Standard Deviation NA small group size	-1.3 units of the HAQ index Standard Deviation 0.58	0.0 units of the HAQ index Standard Deviation NA small group size

OTHER_PRE_SPECIFIED outcome

Timeframe: 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)

Including area under the plasma concentration-time curve over the dosing interval (AUC0-tau)

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=5 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=3 Participants 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	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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=5 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Pharmacokinetics (PK) - Area Under the Plasma concentration-of RPH-104 Under the Subcutaneous Administration	1620000 h*ng/mL Geometric Coefficient of Variation 36.5	3230000 h*ng/mL Geometric Coefficient of Variation 38.2	—	38000 h*ng/mL Geometric Coefficient of Variation 124	762000 h*ng/mL Geometric Coefficient of Variation 152	845000 h*ng/mL Geometric Coefficient of Variation 45

OTHER_PRE_SPECIFIED outcome

Including Area under the active substance concentration-time curve from zero (before drug administration) to infinity (AUC0-∞)

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=5 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=3 Participants 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	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 - 4 mg n=14 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=5 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Pharmacokinetics (PK) - Area Under the Active Substance Concentration- of RPH-104 Under the Subcutaneous Administration	1720000 h*ng/mL Geometric Coefficient of Variation 37.1	3380000 h*ng/mL Geometric Coefficient of Variation 38.1	—	47900 h*ng/mL Geometric Coefficient of Variation 97.9	816000 h*ng/mL Geometric Coefficient of Variation 155	901000 h*ng/mL Geometric Coefficient of Variation 44.3

OTHER_PRE_SPECIFIED outcome

Including Maximum concentration of the active substance (Cmax)

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=4 Participants 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	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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=5 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Pharmacokinetics (PK) - Maximum Concentration of the Active Substance -of RPH-104 Under the Subcutaneous Administration	4860 ng/mL Geometric Coefficient of Variation 18	9760 ng/mL Geometric Coefficient of Variation 38.2	—	142 ng/mL Geometric Coefficient of Variation 110	2220 ng/mL Geometric Coefficient of Variation 155	2380 ng/mL Geometric Coefficient of Variation 47.7

OTHER_PRE_SPECIFIED outcome

Including elimination constant (Kel)

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=5 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=3 Participants 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	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 - 4 mg n=14 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=5 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Pharmacokinetics (PK) of RPH-104 Under the Subcutaneous Administration	0.00317 1/h Standard Deviation 0.000575	0.00294 1/h Standard Deviation 0.000311	—	0.00298 1/h Standard Deviation 0.000573	0.00314 1/h Standard Deviation 0.000622	0.00304 1/h Standard Deviation 0.000241

OTHER_PRE_SPECIFIED outcome

Including Time to reach maximum concentration of the active substance (tmax)

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=4 Participants 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	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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=5 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Pharmacokinetics (PK) -Time to Reach Maximum Concentration of the Active Substance - of RPH-104 Under the Subcutaneous Administration	82.7 hours Interval 24.0 to 122.0	94.4 hours Interval 72.0 to 96.1	—	93.7 hours Interval 8.0 to 120.0	47.5 hours Interval 21.3 to 72.1	84.8 hours Interval 47.1 to 120.0

OTHER_PRE_SPECIFIED outcome

Including terminal half-life (T 1/2)

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=5 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=3 Participants 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	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 - 4 mg n=14 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=5 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Pharmacokinetics (PK) - Terminal Half-life -of RPH-104 Under the Subcutaneous Administration	231 hours Interval 168.0 to 264.0	241 hours Interval 212.0 to 261.0	—	248 hours Interval 153.0 to 285.0	235 hours Interval 170.0 to 274.0	223 hours Interval 205.0 to 256.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and in 24, 72 hours, on Days 5, 6, 15, 29 and 45 after the initiation of treatment with the test drug

Population: Number of valid observations is presented.

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

Outcome measures

Outcome measures
Measure	RPH - 80 mg n=6 Participants RPH-104, 80 mg, subcutaneous single-dose injection. 2 mL (whole vial) of 40 mg/mL RPH-104 solution is injected.	RPH - 160 mg n=5 Participants 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	Voltaren® (Diclofenac) n=9 Participants 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 - 4 mg n=15 Participants RPH-104, 4 mg, subcutaneous single-dose injection. 0.1 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 20 mg n=6 Participants RPH-104, 20 mg, subcutaneous single-dose injection. 0.5 mL of 40 mg/mL RPH-104 solution is injected.	RPH - 40 mg n=6 Participants RPH-104, 40 mg, subcutaneous single-dose injection. 1 mL of 40 mg/mL RPH-104 solution is injected.
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Day 4/ 72 hours	11.846 mg/L Standard Deviation 6.1780	8.678 mg/L Standard Deviation 10.5037	9.279 mg/L Standard Deviation 8.1642	33.894 mg/L Standard Deviation 35.0873	3.408 mg/L Standard Deviation 0.8120	12.900 mg/L Standard Deviation 9.3579
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Baseline value	37.908 mg/L Standard Deviation 25.5594	35.396 mg/L Standard Deviation 32.4800	15.769 mg/L Standard Deviation 18.0878	36.673 mg/L Standard Deviation 31.3545	8.295 mg/L Standard Deviation 6.6212	10.105 mg/L Standard Deviation 14.2834
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Day 2/ 24 hours	28.864 mg/L Standard Deviation 16.1194	12.000 mg/L Standard Deviation 11.5518	22.716 mg/L Standard Deviation 26.9958	35.468 mg/L Standard Deviation 32.2025	20.338 mg/L Standard Deviation 33.3728	24.483 mg/L Standard Deviation 16.3543
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Day 5	8.696 mg/L Standard Deviation 3.6468	6.178 mg/L Standard Deviation 6.4262	8.877 mg/L Standard Deviation 6.3308	32.279 mg/L Standard Deviation 32.6858	3.090 mg/L Standard Deviation 0.9076	7.142 mg/L Standard Deviation 5.7071
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Day 6	4.604 mg/L Standard Deviation 1.3871	3.190 mg/L Standard Deviation 3.0165	8.417 mg/L Standard Deviation 7.0440	29.065 mg/L Standard Deviation 28.1288	2.710 mg/L Standard Deviation 1.6140	3.650 mg/L Standard Deviation 2.8445
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Day 15	5.115 mg/L Standard Deviation 3.5382	4.042 mg/L Standard Deviation 6.1199	6.579 mg/L Standard Deviation 4.4134	21.017 mg/L Standard Deviation 28.4384	2.642 mg/L Standard Deviation 1.4322	3.304 mg/L Standard Deviation 5.8018
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Day 29	5.014 mg/L Standard Deviation 2.8480	10.998 mg/L Standard Deviation 17.3463	7.595 mg/L Standard Deviation 7.9870	16.811 mg/L Standard Deviation 26.3922	7.532 mg/L Standard Deviation 13.0615	2.750 mg/L Standard Deviation 2.9068
Change in the Serum Rate of High-sensitive CRP (Hs-CRP) in Specified Timeframes Day 45	3.093 mg/L Standard Deviation 0.5652	14.500 mg/L Standard Deviation 19.2882	11.734 mg/L Standard Deviation 11.4627	24.958 mg/L Standard Deviation 29.4450	3.570 mg/L Standard Deviation 2.1907	2.445 mg/L Standard Deviation 1.8315

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and in 24, 72 hours and on Day 5, 6, 15, 29 and 45 following the initiation of treatment with the test drug

Population: Number of valid observations is presented.

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