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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Osteoarthritis, Knee, Pain

Intervention / Treatment
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* Drug: CGS-200-1
* Drug: CGS-200-5
* Drug: CGS-200 Vehicle


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CGS-200-1<br>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<br>* 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.<br>* Other names: CGS-200 (1% capsaicin);|
| Experimental: CGS-200-5<br>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<br>* 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.<br>* Other names: CGS-200 (5% capsaicin);|
| Sham Comparator: CGS-200 Vehicle<br>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<br>* CGS-200 Vehicle contains all of the ingredients in CGS-200-1 and CGS-200-5 except for capsaicin.<br>* Other names: CGS-200 (0% capsaicin);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. . | 35 days after the last dose of study drug on Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Days 5, 19, 65 and 94 after the last dose of study drug on Day 4 | 
| 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. | 60 minutes after study drug application on Study Days 1,2,3,4 | 
| 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. | Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4 | 
| 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. | Day 5, 19, 35, 64 and 94 days after the last dose of study drug on Study Day 4 |