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

• Sponsor: Propella Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03528369
• Collaborator: (none)
• Enrollment: 122
• Locations: 6
• Arms: 3
• Actual Duration (Months): 7.6
• Patients Per Site: 20.3
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

This is a multi-center, randomized, double-blind clinical trial to examine the comparative effects on OAKP of CGS-200-1 (1% Capsaicin content) (N=40), CGS-200-5 (5% Capsaicin content) (N=40), and CGS-200 Vehicle (no Capsaicin) (N=40) in subjects with OA of the knees according to the 1986 American College of Rheumatology (ACR) criteria. Assigned doses will be applied at the clinic for 60 minutes on each of four consecutive days.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee; Pain	Drug: CGS-200-1; Drug: CGS-200-5; Drug: CGS-200 Vehicle	Phase 2

Detailed Description

Subjects will be randomized to one of the three Arms in this study: CGS-200-1 or CGS-200-5 or CGS-200 Vehicle (CGS-200-0). All subjects will receive 4 consecutive days of treatment and will then be followed up until the Day 94 visit.

Even though both knee(s) will receive application of study test materials, with regard to reduction in WOMAC pain and VAS pain score associated with study treatments, only one knee will be indicated as the "Study Knee". This will be the knee with the highest WOMAC pain score at screening. If both knees have equal WOMAC pain scores at baseline, then the right knee will be considered the "Study Knee" with regard to WOMAC pain and VAS pain score reduction.

Data will be collected from Day 1 through Day 5 and then again on Days 19, 35, 64 and 94 for efficacy, tolerability, and safety measures. The Investigators, all site staff and Clinical Research Organization (CRO) personnel (except the Medical Monitor providing safety oversight) directly involved in the study will remain blinded to the treatment assignment throughout the trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Double-Blind Clinical Trial to Examine the Comparative Effects on Osteoarthritic Knee Pain of CGS-200-1 (1% Capsaicin Topical Liquid), CGS-200-5 (5% Capsaicin Topical Liquid), and CGS-200-0 (Vehicle, No Capsaicin)
• Actual Study Start Date: May 14, 2018
• Actual Primary Completion Date: Oct 14, 2018
• Actual Study Completion Date: Dec 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CGS-200-1 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.	Drug: 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.; Other Names: CGS-200 (1% capsaicin)
Experimental: CGS-200-5 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.	Drug: 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.; Other Names: CGS-200 (5% capsaicin)
Sham Comparator: CGS-200 Vehicle 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.	Drug: CGS-200 Vehicle; CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.; Other Names: CGS-200 (0% capsaicin)

Outcome Measures

Primary Outcome Measures

1. Primary Efficacy Endpoint: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35 [35 days after the last dose of study drug on Day 4]

   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. .

Secondary Outcome Measures

1. 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. [Days 5, 19, 65 and 94 after the last dose of study drug on Day 4]

   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.

2. Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. [60 minutes after study drug application on Study Days 1,2,3,4]

   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.

3. Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. [Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4]

   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.

4. Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. [Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4]

   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.

Other Outcome Measures

1. Number of Subjects With Skin Reactions of Erythema or Pruritus. [Study Day 1 through Study Day 35 after the first application of study drug (Study Day 1)]

   Investigator reports of erythema or pruritus at the site of study drug application.

2. Number of Subjects With Durability of Efficacy Response [Days 35, 64 and 94 day after the last dose of study drug on Study Day 4]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Osteoarthritis (OA) of both knees;

• OA of both knees must be confirmed by tibiofemoral joint radiographs obtained within the past 6 months;

• Rheumatoid factor (RF) negative and Erythrocyte sedimentation rate (ESR) <40 mm/hr;

• Chronic knee pain in at least 1 knee for > 3 months;

• WOMAC pain score of > 250 (using VAS WOMAC format) at screening, and at baseline, in at least one knee;

• Knee pain score of > 5 on the NRS pain scale at screening, and at baseline, in at least one knee;

• Knee pain is not potentially due to acute trauma unrelated to OA (no acute traumatic knee injury in medical history);

• No burning-stinging pain, unrelated to subject's knee pain, at intended site of application;

• Knee pain must be greater than pain in any other part of subject's body;

• American College of Rheumatology (ACR) global functional status I, II, or III (excluding IV).

Exclusion Criteria:

• Spontaneously improving or rapidly deteriorating OA of the knee;

• Rheumatoid or psoriatic arthritis, or a form of arthritis (e.g. gout, pseudogout), Paget's disease of bone, or any other disease affecting the joints that are inconsistent with a diagnosis of idiopathic OA;

• Labile or poorly controlled hypertension;

• Use of steroids for 1 month prior to screening, or intraarticular-visco-supplementation within 3 months prior to screening;

• Used any capsaicin-containing product on or in the vicinity of the knee within 4 weeks prior to screening;

• Used topically applied products (including emollients or moisturizers) on or in the vicinity of the knees or shaved the knees within 2 days prior to the first application of study drug; or an open wound near the knee; cutaneous erythema or edema; any inflammatory skin lesions such as eczema or psoriasis; cutaneous infections; or any other compromise of the skin;

• Requires or anticipates any surgical procedure within 3 months prior to screening, has had surgery on the affected joint within 6 months prior to screening, has a prosthesis in either knee, or would require surgery while participating in the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research of West Florida	Clearwater	Florida	United States	33765
2	Clinical Research of West Florida, Inc.	Tampa	Florida	United States	33603
3	McIlwain Medical Group	Tampa	Florida	United States	33613
4	CTI Clinical Research Center	Cincinnati	Ohio	United States	45212
5	Radiant Research, Inc.	Dallas	Texas	United States	75234
6	Radiant Research, Inc.	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Propella Therapeutics

Investigators

• Study Director: Vice President Clinical Operations, Vizuri Health Sciences

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 24, 2019
• Study Protocol - Aug 1, 2018

More Information

Publications

None provided.

• Responsible Party: Propella Therapeutics
• ClinicalTrials.gov Identifier: NCT03528369
• Other Study ID Numbers: VZU00025
• First Posted: May 17, 2018
• Last Update Posted: Oct 27, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Osteoarthritis, Knee; Capsaicin

Study Results

Participant Flow

Recruitment Details	Subjects were recruited at 6 investigative sites in the US.
Pre-assignment Detail	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

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 Participants	40	42	40	122
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59.4	61.1	59.5	60
Sex: Female, Male (Count of Participants)
Female	29 72.5%	24 57.1%	24 60%	77 63.1%
Male	11 27.5%	18 42.9%	16 40%	45 36.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5%	10 23.8%	8 20%	20 16.4%
Not Hispanic or Latino	38 95%	32 76.2%	32 80%	102 83.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 2.5%	0 0%	1 2.5%	2 1.6%
Native Hawaiian or Other Pacific Islander	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%	33 78.6%	22 55%	83 68%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	40 100%	42 100%	40 100%	122 100%
Baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	357.0	350.7	346.8	351.5

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.
Measure Participants	39	40	39
Mean (Full Range) [units on a scale]	-130.7	-159.7	-99.0

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.
Measure Participants	40	42	40
Day 5 WOMAC Pain Score Change from Baseline	-113.1	-157.5	-64.5
Day 19 WOMAC Pain Score Change from Baseline	-131.8	-171.7	-66.4
Day 64 WOMAC Pain Score Change from Baseline	-79.5	-169.8	75.4
Day 94 WOMAC Pain Score Change from Baseline	-111.8	-147.6	-80.1

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.
Measure Participants	40	42	40
Mean Burning-Stinging Pain on Day 1	1.36	2.70	0.36
Mean Burning-Stinging Pain on Day 2	0.75	1.71	0.49
Mean Burning-Stinging Pain Day 3	0.70	1.53	0.22
Mean Burning-Stinging Pain Day 4	0.56	1.47	0.20

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.
Measure Participants	40	42	40
Day 5 WOMAC Stiffness Score Change from Baseline	-50.7	-59.6	-25.6
Day 19 WOMAC Stiffness Score Change from Baseline	-52.2	-65.5	-26.8
Day 35 WOMAC Stiffness Score Change from Baseline	-46.0	-54.8	-39.8
Day 64 WOMAC Stiffness Score Change from Baseline	-32.2	-59.5	-28.1
Day 94 WOMAC Stiffness Score Change from Baseline	-42.7	-56.8	-31.9

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.
Measure Participants	40	42	40
Day 5 WOMAC Function Score Change from Baseline	-385.0	-499.0	-198.1
Day 19 WOMAC Function Score Change from Baseline	-398.7	-583.7	-192.1
Day 35 WOMAC Function Score Change from Baseline	-367.8	-523.0	-296.9
Day 64 WOMAC Function Score Change from Baseline	-218.9	-515.9	-213.7
Day 94 WOMAC Function Score Change from Baseline	-337.5	-506.5	-233

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.
Measure Participants	40	42	40
Erythema	1 2.5%	1 2.4%	0 0%
Pruritus	2 5%	2 4.8%	0 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.
Measure Participants	40	42	40
Responders	15 37.5%	19 45.2%	11 27.5%
Non-Responders	25 62.5%	22 52.4%	29 72.5%
Responders	5 12.5%	23 54.8%	9 22.5%
Non-Responders	35 87.5%	18 42.9%	31 77.5%
Responders	10 25%	18 42.9%	10 25%
Non-Responders	30 75%	23 54.8%	30 75%

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.
Measure Participants	40	42	40
Day 5 WOMAC Total Score Change from Baseline	-548.8	-716.1	-288.1
Day 19 WOMAC Total Score Change from Baseline	-582.8	-820.9	-285.3
Day 35 WOMAC Total Score Change from Baseline	-544.5	-737.5	-435.8
Day 64 WOMAC Total Score Change from Baseline	-330.6	-745.2	-317.2
Day 94 WOMAC Total Score Change from Baseline	-491.9	-710.8	-345.9

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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/42 (0%)		0/40 (0%)
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%)		0/42 (0%)		0/42 (0%)
Other (Not Including 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	36/40 (90%)		41/42 (97.6%)		24/40 (60%)
General disorders
Application Site Pain	30/40 (75%)	30	40/42 (95.2%)	40	20/40 (50%)	20
Application site paraesthesia	2/40 (5%)	2	4/42 (9.5%)	4	2/40 (5%)	2
Application site pruritus	3/40 (7.5%)	3	2/42 (4.8%)	2	0/40 (0%)	0
Infections and infestations
Nasopharyngitis	2/40 (5%)	2	0/42 (0%)	0	0/40 (0%)	0
Upper respiratory tract infection	0/40 (0%)	0	0/42 (0%)	0	2/40 (5%)	2
Injury, poisoning and procedural complications
Fall	0/40 (0%)	0	2/42 (4.8%)	2	0/40 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/40 (0%)	0	4/42 (9.5%)	4	0/40 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.