Osteoarthritis, Knee, Pain
Conditions
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.
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.
Interventions
DRUGCGS-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.
DRUGCGS-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.
DRUGCGS-200 Vehicle
CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.
Sponsors
Propella Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 40 |
| 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.
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. | 42 |
| 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.
CGS-200 Vehicle: CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin. | 40 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | CGS-200-1 | CGS-200-5 | CGS-200 Vehicle | Total |
|---|---|---|---|---|
| Age, Continuous | 59.4 years | 61.1 years | 59.5 years | 60 years |
| Baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score | 357.0 units on a scale | 350.7 units on a scale | 346.8 units on a scale | 351.5 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 10 Participants | 8 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 32 Participants | 32 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 9 Participants | 17 Participants | 37 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 33 Participants | 22 Participants | 83 Participants |
| Region of Enrollment United States | 40 participants | 42 participants | 40 participants | 122 participants |
| Sex: Female, Male Female | 29 Participants | 24 Participants | 24 Participants | 77 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 16 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 42 | 0 / 40 |
| other Total, other adverse events | 36 / 40 | 41 / 42 | 24 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 42 | 0 / 42 |
Outcome results
Primary
Primary Efficacy Endpoint: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35
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
Population: All subjects that received at least one dose of study drug and had at least one evaluable post-dosing efficacy endpoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CGS-200-1 | Primary Efficacy Endpoint: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35 | -130.7 units on a scale |
| CGS-200-5 | Primary Efficacy Endpoint: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35 | -159.7 units on a scale |
| CGS-200 Vehicle | Primary Efficacy Endpoint: Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score From Baseline to Day 35 | -99.0 units on a scale |
Secondary
Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug.
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CGS-200-1 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain on Day 2 | 0.75 units on a scale |
| CGS-200-1 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain Day 4 | 0.56 units on a scale |
| CGS-200-1 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain Day 3 | 0.70 units on a scale |
| CGS-200-1 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain on Day 1 | 1.36 units on a scale |
| CGS-200-5 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain on Day 2 | 1.71 units on a scale |
| CGS-200-5 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain on Day 1 | 2.70 units on a scale |
| CGS-200-5 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain Day 4 | 1.47 units on a scale |
| CGS-200-5 | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain Day 3 | 1.53 units on a scale |
| CGS-200 Vehicle | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain Day 4 | 0.20 units on a scale |
| CGS-200 Vehicle | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain Day 3 | 0.22 units on a scale |
| CGS-200 Vehicle | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain on Day 1 | 0.36 units on a scale |
| CGS-200 Vehicle | Patient Reported Burning-Stinging Pain (BSP) During Application of Study Drug. | Mean Burning-Stinging Pain on Day 2 | 0.49 units on a scale |
Secondary
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.
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CGS-200-1 | 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. | Day 19 WOMAC Pain Score Change from Baseline | -131.8 units on a scale |
| CGS-200-1 | 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. | Day 5 WOMAC Pain Score Change from Baseline | -113.1 units on a scale |
| CGS-200-1 | 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. | Day 64 WOMAC Pain Score Change from Baseline | -79.5 units on a scale |
| CGS-200-1 | 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. | Day 94 WOMAC Pain Score Change from Baseline | -111.8 units on a scale |
| CGS-200-5 | 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. | Day 94 WOMAC Pain Score Change from Baseline | -147.6 units on a scale |
| CGS-200-5 | 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. | Day 19 WOMAC Pain Score Change from Baseline | -171.7 units on a scale |
| CGS-200-5 | 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. | Day 64 WOMAC Pain Score Change from Baseline | -169.8 units on a scale |
| CGS-200-5 | 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. | Day 5 WOMAC Pain Score Change from Baseline | -157.5 units on a scale |
| CGS-200 Vehicle | 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. | Day 64 WOMAC Pain Score Change from Baseline | 75.4 units on a scale |
| CGS-200 Vehicle | 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. | Day 19 WOMAC Pain Score Change from Baseline | -66.4 units on a scale |
| CGS-200 Vehicle | 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. | Day 5 WOMAC Pain Score Change from Baseline | -64.5 units on a scale |
| CGS-200 Vehicle | 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. | Day 94 WOMAC Pain Score Change from Baseline | -80.1 units on a scale |
Secondary
Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores.
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 64 WOMAC Function Score Change from Baseline | -218.9 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 35 WOMAC Function Score Change from Baseline | -367.8 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 5 WOMAC Function Score Change from Baseline | -385.0 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 19 WOMAC Function Score Change from Baseline | -398.7 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 94 WOMAC Function Score Change from Baseline | -337.5 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 35 WOMAC Function Score Change from Baseline | -523.0 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 5 WOMAC Function Score Change from Baseline | -499.0 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 19 WOMAC Function Score Change from Baseline | -583.7 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 64 WOMAC Function Score Change from Baseline | -515.9 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 94 WOMAC Function Score Change from Baseline | -506.5 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 94 WOMAC Function Score Change from Baseline | -233 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 64 WOMAC Function Score Change from Baseline | -213.7 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 5 WOMAC Function Score Change from Baseline | -198.1 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 35 WOMAC Function Score Change from Baseline | -296.9 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Function Scores. | Day 19 WOMAC Function Score Change from Baseline | -192.1 units on a scale |
Secondary
Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores.
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 19 WOMAC Stiffness Score Change from Baseline | -52.2 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 64 WOMAC Stiffness Score Change from Baseline | -32.2 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 5 WOMAC Stiffness Score Change from Baseline | -50.7 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 35 WOMAC Stiffness Score Change from Baseline | -46.0 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 94 WOMAC Stiffness Score Change from Baseline | -42.7 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 35 WOMAC Stiffness Score Change from Baseline | -54.8 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 64 WOMAC Stiffness Score Change from Baseline | -59.5 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 94 WOMAC Stiffness Score Change from Baseline | -56.8 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 19 WOMAC Stiffness Score Change from Baseline | -65.5 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 5 WOMAC Stiffness Score Change from Baseline | -59.6 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 94 WOMAC Stiffness Score Change from Baseline | -31.9 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 5 WOMAC Stiffness Score Change from Baseline | -25.6 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 19 WOMAC Stiffness Score Change from Baseline | -26.8 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 35 WOMAC Stiffness Score Change from Baseline | -39.8 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Stiffness Scores. | Day 64 WOMAC Stiffness Score Change from Baseline | -28.1 units on a scale |
Other Pre-specified
Number of Subjects With Durability of Efficacy Response
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
Population: All subjects that received at least one dose of study drug and had at least one evaluable post-dosing efficacy endpoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| CGS-200-1 | Number of Subjects With Durability of Efficacy Response | Day 35 | Non-Responders | 25 Participants |
| CGS-200-1 | Number of Subjects With Durability of Efficacy Response | Day 35 | Responders | 15 Participants |
| CGS-200-1 | Number of Subjects With Durability of Efficacy Response | Day 64 Responders | Responders | 5 Participants |
| CGS-200-1 | Number of Subjects With Durability of Efficacy Response | Day 64 Responders | Non-Responders | 35 Participants |
| CGS-200-1 | Number of Subjects With Durability of Efficacy Response | Day 94 Responders | Responders | 10 Participants |
| CGS-200-1 | Number of Subjects With Durability of Efficacy Response | Day 94 Responders | Non-Responders | 30 Participants |
| CGS-200-5 | Number of Subjects With Durability of Efficacy Response | Day 94 Responders | Non-Responders | 23 Participants |
| CGS-200-5 | Number of Subjects With Durability of Efficacy Response | Day 35 | Non-Responders | 22 Participants |
| CGS-200-5 | Number of Subjects With Durability of Efficacy Response | Day 94 Responders | Responders | 18 Participants |
| CGS-200-5 | Number of Subjects With Durability of Efficacy Response | Day 35 | Responders | 19 Participants |
| CGS-200-5 | Number of Subjects With Durability of Efficacy Response | Day 64 Responders | Non-Responders | 18 Participants |
| CGS-200-5 | Number of Subjects With Durability of Efficacy Response | Day 64 Responders | Responders | 23 Participants |
| CGS-200 Vehicle | Number of Subjects With Durability of Efficacy Response | Day 35 | Non-Responders | 29 Participants |
| CGS-200 Vehicle | Number of Subjects With Durability of Efficacy Response | Day 64 Responders | Responders | 9 Participants |
| CGS-200 Vehicle | Number of Subjects With Durability of Efficacy Response | Day 94 Responders | Non-Responders | 30 Participants |
| CGS-200 Vehicle | Number of Subjects With Durability of Efficacy Response | Day 64 Responders | Non-Responders | 31 Participants |
| CGS-200 Vehicle | Number of Subjects With Durability of Efficacy Response | Day 35 | Responders | 11 Participants |
| CGS-200 Vehicle | Number of Subjects With Durability of Efficacy Response | Day 94 Responders | Responders | 10 Participants |
Other Pre-specified
Number of Subjects With Skin Reactions of Erythema or Pruritus.
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)
Population: All subjects who have received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CGS-200-1 | Number of Subjects With Skin Reactions of Erythema or Pruritus. | Erythema | 1 participants |
| CGS-200-1 | Number of Subjects With Skin Reactions of Erythema or Pruritus. | Pruritus | 2 participants |
| CGS-200-5 | Number of Subjects With Skin Reactions of Erythema or Pruritus. | Erythema | 1 participants |
| CGS-200-5 | Number of Subjects With Skin Reactions of Erythema or Pruritus. | Pruritus | 2 participants |
| CGS-200 Vehicle | Number of Subjects With Skin Reactions of Erythema or Pruritus. | Erythema | 0 participants |
| CGS-200 Vehicle | Number of Subjects With Skin Reactions of Erythema or Pruritus. | Pruritus | 0 participants |
Post Hoc
Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function).
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
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 64 WOMAC Total Score Change from Baseline | -330.6 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 94 WOMAC Total Score Change from Baseline | -491.9 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 19 WOMAC Total Score Change from Baseline | -582.8 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 35 WOMAC Total Score Change from Baseline | -544.5 units on a scale |
| CGS-200-1 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 5 WOMAC Total Score Change from Baseline | -548.8 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 19 WOMAC Total Score Change from Baseline | -820.9 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 64 WOMAC Total Score Change from Baseline | -745.2 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 35 WOMAC Total Score Change from Baseline | -737.5 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 94 WOMAC Total Score Change from Baseline | -710.8 units on a scale |
| CGS-200-5 | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 5 WOMAC Total Score Change from Baseline | -716.1 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 94 WOMAC Total Score Change from Baseline | -345.9 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 64 WOMAC Total Score Change from Baseline | -317.2 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 19 WOMAC Total Score Change from Baseline | -285.3 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 35 WOMAC Total Score Change from Baseline | -435.8 units on a scale |
| CGS-200 Vehicle | Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index Total Scores (Pain, Stiffness and Function). | Day 5 WOMAC Total Score Change from Baseline | -288.1 units on a scale |