A Phase 2 Clinical Trial Examining the Effects on Osteoarthritic Knee Pain of CGS-200-1, CGS-200-5 and Vehicle Control

• ClinicalTrials.gov Identifier: NCT03528369
• Recruitment Status: Completed
• First Posted: May 17, 2018
• Results First Posted: December 17, 2019
• Last Update Posted: October 27, 2020
• Sponsor: Propella Therapeutics
• Information provided by (Responsible Party): Propella Therapeutics

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Osteoarthritis, Knee; Pain
• Interventions: Drug: CGS-200-1; Drug: CGS-200-5; Drug: CGS-200 Vehicle
• Enrollment: 122

Participant Flow

Recruitment Details	Subjects were recruited at 6 investigative sites in the US.
Pre-assignment Details	Subjects were randomized to receive one of three treatments after the investigator deemed them to qualify for the study.

Arm/Group Title	CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description	CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Period Title: Overall Study
Started	40	42	40
Completed	37	41	40
Not Completed	3	1	0
Reason Not Completed
Withdrawal by Subject	2	0	0
Lost to Follow-up	1	0	0
Adverse Event	0	1	0

Baseline Characteristics

Arm/Group Title		CGS-200-1	CGS-200-5	CGS-200 Vehicle	Total
Arm/Group Description		CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.	Total of all reporting groups
Overall Number of Baseline Participants		40	42	40	122
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	40 participants	42 participants	40 participants	122 participants
		59.4; (41 to 75)	61.1; (44 to 74)	59.5; (40 to 72)	60; (40 to 75)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	42 participants	40 participants	122 participants
	Female	29 72.5%	24 57.1%	24 60.0%	77 63.1%
	Male	11 27.5%	18 42.9%	16 40.0%	45 36.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	42 participants	40 participants	122 participants
	Hispanic or Latino	2 5.0%	10 23.8%	8 20.0%	20 16.4%
	Not Hispanic or Latino	38 95.0%	32 76.2%	32 80.0%	102 83.6%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	40 participants	42 participants	40 participants	122 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	1 2.5%	0 0.0%	1 2.5%	2 1.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	11 27.5%	9 21.4%	17 42.5%	37 30.3%
	White	28 70.0%	33 78.6%	22 55.0%	83 68.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	40 participants	42 participants	40 participants	122 participants
		40	42	40	122
Baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score [1]; Mean (Full Range); Unit of measure: Units on a scale
	Number Analyzed	40 participants	42 participants	40 participants	122 participants
		357.0; (260 to 486)	350.7; (266 to 460)	346.8; (254 to 490)	351.5; (254 to 490)
		[1] Measure Description: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score is 5 questions relating to pain that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 500. The higher the number the worse the outcome.

Outcome Measures

1. Primary Outcome

Title	Primary Efficacy Endpoint: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35
Description	The Primary Efficacy endpoint of this study will be to examine the extent of change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, relative to baseline, provided by once daily, one-hour application of Vehicle (CGS-200-0), CGS-200-1 and CGS-200-5 at Baseline (< 30 minutes prior to first daily application) and Day 35 (31 days after fourth daily application). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score is 5 questions relating to pain that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 500. Reduction in pain is expressed as a difference from baseline to Study Day 35. Positive numbers indicate increases and negative numbers indicate decreases. .
Time Frame	35 days after the last dose of study drug on Day 4

Outcome Measure Data

Analysis Population Description

All subjects that received at least one dose of study drug and had at least one evaluable post-dosing efficacy endpoint.

Arm/Group Title	CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:	CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed	39	40	39
Mean (Full Range); Unit of Measure: units on a scale
	-130.7; (-354 to 54)	-159.7; (-376 to 34)	-99.0; (-328 to 73)

2. Secondary Outcome

Title	Secondary Efficacy Endpoint #1: Extent of Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 5, 19, 64 and 94.
Description	The extent of change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, relative to baseline, provided by once daily, one-hour application of CGS-200-0, CGS-200-1 and CGS-200-5 from Baseline to Day 5, 19, 64 and Day 94. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score is 5 questions relating to pain that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 500. Positive numbers indicate increases and negative numbers indicate decreases.
Time Frame	Days 5, 19, 65 and 94 after the last dose of study drug on Day 4

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of study drug. Differences in subjects is due to subjects who withdrew from the study prior to the efficacy assessment.

Arm/Group Title		CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:		CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed		40	42	40
Mean (Full Range); Unit of Measure: units on a scale
Day 5 WOMAC Pain Score Change from Baseline	Number Analyzed	40 participants	41 participants	40 participants
		-113.1; (-359 to 42)	-157.5; (-367 to 40)	-64.5; (-409 to 57)
Day 19 WOMAC Pain Score Change from Baseline	Number Analyzed	40 participants	42 participants	40 participants
		-131.8; (-338 to 75)	-171.7; (-388 to 21)	-66.4; (-289 to 72)
Day 64 WOMAC Pain Score Change from Baseline	Number Analyzed	40 participants	42 participants	40 participants
		-79.5; (-345 to 132)	-169.8; (-358 to 34)	75.4; (-291 to 107)
Day 94 WOMAC Pain Score Change from Baseline	Number Analyzed	37 participants	39 participants	40 participants
		-111.8; (-349 to 72)	-147.6; (-378 to 98)	-80.1; (-332 to 90)

3. Secondary Outcome

Title	Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug.
Description	The average amount of burning-sting pain as reported by the subject using a 0 - 10 numerical rating scale (NRS). Higher scores indicate more pain.
Time Frame	60 minutes after study drug application on Study Days 1,2,3,4

Outcome Measure Data

Analysis Population Description

All subjects who have received at least one dose of study drug. The number of subjects analyzed differs in some cases due to missing data.

Arm/Group Title		CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:		CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed		40	42	40
Mean (Full Range); Unit of Measure: units on a scale
Mean Burning-Stinging Pain on Day 1	Number Analyzed	40 participants	42 participants	40 participants
		1.36; (0 to 7.75)	2.70; (0 to 7.25)	0.36; (0 to 3.25)
Mean Burning-Stinging Pain on Day 2	Number Analyzed	40 participants	40 participants	39 participants
		0.75; (0 to 3.75)	1.71; (0 to 7.75)	0.49; (0 to 5.75)
Mean Burning-Stinging Pain Day 3	Number Analyzed	40 participants	40 participants	39 participants
		0.70; (0 to 3.50)	1.53; (0 to 7.25)	0.22; (0 to 2.50)
Mean Burning-Stinging Pain Day 4	Number Analyzed	40 participants	42 participants	40 participants
		0.56; (0 to 2.50)	1.47; (0 to 7.00)	0.20; (0 to 3.00)

4. Secondary Outcome

Title	Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores.
Description	Day 5, 19, 35, 64 and 94 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score is 2 questions relating to stiffness that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 200. Positive numbers indicate increases and negative numbers indicate decreases.
Time Frame	Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4

Outcome Measure Data

Analysis Population Description

All subjects that received at least one dose of study drug and had at least one evaluable post-dosing efficacy endpoint. Differences in number of subjects is due to subjects early withdrawal from the study.

Arm/Group Title		CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:		CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed		40	42	40
Mean (Full Range); Unit of Measure: units on a scale
Day 5 WOMAC Stiffness Score Change from Baseline	Number Analyzed	40 participants	41 participants	40 participants
		-50.7; (-147 to 58)	-59.6; (-166 to 32)	-25.6; (-188 to 39)
Day 19 WOMAC Stiffness Score Change from Baseline	Number Analyzed	39 participants	40 participants	39 participants
		-52.2; (-152 to 109)	-65.5; (-161 to 65)	-26.8; (-152 to 29)
Day 35 WOMAC Stiffness Score Change from Baseline	Number Analyzed	39 participants	40 participants	39 participants
		-46.0; (-154 to 78)	-54.8; (-137 to 33)	-39.8; (-158 to 30)
Day 64 WOMAC Stiffness Score Change from Baseline	Number Analyzed	38 participants	40 participants	39 participants
		-32.2; (-150 to 114)	-59.5; (-162 to 29)	-28.1; (-158 to 42)
Day 94 WOMAC Stiffness Score Change from Baseline	Number Analyzed	37 participants	39 participants	40 participants
		-42.7; (-151 to 37)	-56.8; (-166 to 45)	-31.9; (-159 to 42)

5. Secondary Outcome

Title	Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores.
Description	Day 5, 19, 35, 64 and 94 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Function score is 17 questions relating to physical function that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 1700. Positive numbers indicate increases and negative numbers indicate decreases.
Time Frame	Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4

Outcome Measure Data

Analysis Population Description

All subjects that received at least one dose of study drug and had at least one evaluable post-dosing efficacy endpoint. Differences in number of subjects is due to subjects early withdrawal from the study.

Arm/Group Title		CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:		CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed		40	42	40
Mean (Full Range); Unit of Measure: units on a scale
Day 5 WOMAC Function Score Change from Baseline	Number Analyzed	40 participants	41 participants	40 participants
		-385.0; (-1174 to 346)	-499.0; (-1397 to 59)	-198.1; (-1343 to 223)
Day 19 WOMAC Function Score Change from Baseline	Number Analyzed	39 participants	40 participants	39 participants
		-398.7; (-1275 to 501)	-583.7; (-1415 to 100)	-192.1; (-1219 to 315)
Day 35 WOMAC Function Score Change from Baseline	Number Analyzed	39 participants	40 participants	39 participants
		-367.8; (-1240 to 456)	-523.0; (-1397 to 286)	-296.9; (-1278 to 279)
Day 64 WOMAC Function Score Change from Baseline	Number Analyzed	38 participants	40 participants	39 participants
		-218.9; (-1286 to 796)	-515.9; (-1261 to 299)	-213.7; (-901 to 357)
Day 94 WOMAC Function Score Change from Baseline	Number Analyzed	37 participants	39 participants	39 participants
		-337.5; (-1273 to 249)	-506.5; (-1406 to 191)	-233; (-1297 to 349)

6. Other Pre-specified Outcome

Title	Number of Subjects With Skin Reactions of Erythema or Pruritus.
Description	Investigator reports of erythema or pruritus at the site of study drug application.
Time Frame	Study Day 1 through Study Day 35 after the first application of study drug (Study Day 1)

Outcome Measure Data

Analysis Population Description

All subjects who have received at least one dose of study drug

Arm/Group Title	CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:	CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed	40	42	40
Measure Type: Number; Unit of Measure: participants
Erythema	1	1	0
Pruritus	2	2	0

7. Other Pre-specified Outcome

Title	Number of Subjects With Durability of Efficacy Response
Description	Subjects who had a clinical response (i.e., reduction of at least 50% in WOMAC pain score) at the Day 5 visit and who remained at this reduction of pain score or lower at Days 19, 35, 64, and the Day 94 visit were considered to have a durable clinical response through Day 94. Subjects who had a clinical response at no more than one of the post Day 5 visits were considered to have a durable response through the last day at which reduction in WOMAC pain score is at least 50%. Subjects who had less than 50% WOMAC pain score reduction on two or more of the post Day 5 visits were considered to have failed to achieve a durable clinical response.
Time Frame	Days 35, 64 and 94 day after the last dose of study drug on Study Day 4

Outcome Measure Data

Analysis Population Description

All subjects that received at least one dose of study drug and had at least one evaluable post-dosing efficacy endpoint.

Arm/Group Title		CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:		CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed		40	42	40
Measure Type: Count of Participants; Unit of Measure: Participants
Day 35	Number Analyzed	40 participants	41 participants	40 participants
	Responders	15 37.5%	19 46.3%	11 27.5%
	Non-Responders	25 62.5%	22 53.7%	29 72.5%
Day 64 Responders	Number Analyzed	40 participants	41 participants	40 participants
	Responders	5 12.5%	23 56.1%	9 22.5%
	Non-Responders	35 87.5%	18 43.9%	31 77.5%
Day 94 Responders	Number Analyzed	40 participants	41 participants	40 participants
	Responders	10 25.0%	18 43.9%	10 25.0%
	Non-Responders	30 75.0%	23 56.1%	30 75.0%

8. Post-Hoc Outcome

Title	Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function).
Description	Day 5, 19, 35, 64 and 94 Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index total scores (pain, stiffness and function) from Baseline. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score is 24 questions relating to pain, stiffness and physical function that the subject responds to using a 100mm visual analogue scale. The minimum score is 0 and the maximum score is 2400. Positive numbers indicate increases and negative numbers indicate decreases.
Time Frame	Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4

Outcome Measure Data

Analysis Population Description

All subjects that received at least one dose of study drug and had at least one evaluable post-dosing efficacy endpoint. Differences in number of subjects is due to subjects early withdrawal from the study.

Arm/Group Title		CGS-200-1	CGS-200-5	CGS-200 Vehicle
Arm/Group Description:		CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.	CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.	CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Overall Number of Participants Analyzed		40	42	40
Mean (Full Range); Unit of Measure: units on a scale
Day 5 WOMAC Total Score Change from Baseline	Number Analyzed	40 participants	41 participants	40 participants
		-548.8; (-1747 to 572)	-716.1; (-1928 to 22)	-288.1; (-1940 to 285)
Day 19 WOMAC Total Score Change from Baseline	Number Analyzed	39 participants	40 participants	39 participants
		-582.8; (-1747 to 572)	-820.9; (-1961 to 121)	-285.3; (-1660 to 406)
Day 35 WOMAC Total Score Change from Baseline	Number Analyzed	39 participants	40 participants	39 participants
		-544.5; (-1748 to 366)	-737.5; (-1899 to 353)	-435.8; (-1747 to 370)
Day 64 WOMAC Total Score Change from Baseline	Number Analyzed	38 participants	40 participants	39 participants
		-330.6; (-1781 to 901)	-745.2; (-1759 to 337)	-317.2; (-1261 to 506)
Day 94 WOMAC Total Score Change from Baseline	Number Analyzed	37 participants	39 participants	39 participants
		-491.9; (-1769 to 331)	-710.8; (-1939 to 314)	-345.9; (-1769 to 331)

Adverse Events

Time Frame	AEs were captured from start of study drug treatment through Day 94
Adverse Event Reporting Description	Severity was graded using the Rheumatology Common Toxicity Criteria (RCTC) version 2.0
Arm/Group Title	CGS-200-1		CGS-200-5		CGS-200 Vehicle
Arm/Group Description	CGS-200-1 (1% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-1: CGS-200-1 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 1% for this study.		CGS-200-5 (5% Capsaicin content), a topical analgesic liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200-5: CGS-200-5 is a multi-component formulation in which the active ingredient for the intended therapeutic effect is capsaicin at a level of 5% for this study.		CGS-200 Vehicle (no Capsaicin), a topical liquid. A single dose will be topically applied to both knees for 60 minutes on Visit 2 on Day 1, Day 2, Day 3, and Day 4. CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
All-Cause Mortality
	CGS-200-1		CGS-200-5		CGS-200 Vehicle
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/40 (0.00%)		0/42 (0.00%)		0/40 (0.00%)
Serious Adverse Events
	CGS-200-1		CGS-200-5		CGS-200 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0.00%)		0/42 (0.00%)		0/42 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	CGS-200-1		CGS-200-5		CGS-200 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/40 (90.00%)		41/42 (97.62%)		24/40 (60.00%)
General disorders
Application Site Pain † 1	30/40 (75.00%)	30	40/42 (95.24%)	40	20/40 (50.00%)	20
Application site paraesthesia † 1	2/40 (5.00%)	2	4/42 (9.52%)	4	2/40 (5.00%)	2
Application site pruritus † 1	3/40 (7.50%)	3	2/42 (4.76%)	2	0/40 (0.00%)	0
Infections and infestations
Nasopharyngitis † 1	2/40 (5.00%)	2	0/42 (0.00%)	0	0/40 (0.00%)	0
Upper respiratory tract infection † 1	0/40 (0.00%)	0	0/42 (0.00%)	0	2/40 (5.00%)	2
Injury, poisoning and procedural complications
Fall † 1	0/40 (0.00%)	0	2/42 (4.76%)	2	0/40 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/40 (0.00%)	0	4/42 (9.52%)	4	0/40 (0.00%)	0
1 Term from vocabulary, MedDRA 10.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Sponsor can review results and communications prior to public release, and Sponsor can embargo communications regarding trial results for a period that is less than or equal to 45 days from the time submitted to the Sponsor for review. At all times, PIs retain editorial control of all publications and have a right to publish the study data, subject only to Sponsor's time-limited right to protect its intellectual property rights and prevent disclosure of Sponsor's confidential information.

Results Point of Contact

• Name/Title: Vice President Clinical Operations
• Organization: Vizuri Health Sciences
• Phone: 919-397-4782
• EMail: twarneke@vizuriusa.com

• Responsible Party: Propella Therapeutics
• ClinicalTrials.gov Identifier: NCT03528369
• Other Study ID Numbers: VZU00025
• First Submitted: March 20, 2018
• First Posted: May 17, 2018
• Results First Submitted: December 2, 2019
• Results First Posted: December 17, 2019
• Last Update Posted: October 27, 2020