3VM for Treatment of Chronic Osteoarthritis Knee Pain

Study Overview
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Brief Summary
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A double-blind, placebo-controlled, randomized dose ranging study for the use of 3VM1001 Cream, 2g three times daily, 3g three times daily, or 3g four times daily for treatment of chronic pain associated with osteoarthritis of the knee compared to inactive placebo.

Detailed Description
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The study is a double-blind, placebo-controlled, dose ranging study for the use of 3VM1001 Cream, 2g three times daily, 3g three times daily, or 3g four times daily for the treatment of chronic pain associated with osteoarthritis of the knee compared to the inactive vehicle as a placebo. A maximum of 120 subjects will be enrolled. Subjects will self-treat for 7 (+2) days, applied in the morning and at bed time. The active pharmaceutical ingredient is copper. The proposed doses in the study are less than 2% of the upper limit of the RDA (0.9 mg/day, upper limit 10mg/day). Rescue medication is acetaminophen, up to  2g daily (Up to six Tylenol Regular Strength tablets).

Official Title
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A Double-Blind, Placebo-Controlled, Randomized Study to Evaluate the Safety and Efficacy of 3VM1001 Cream for the Treatment of Chronic Pain Caused by Osteoarthritis of the Knee: A Dose Ranging Study

Conditions
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Arthritis, Degenerative

Intervention / Treatment
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* Drug: Experimental: 3VM1001 active 2g Cream 3 times daily
* Drug: Experimental: 3VM1001 active 3g Cream 3 times daily
* Drug: Experimental: 3VM1001 active 3g Cream 4 times daily
* Drug: Placebo: 3VM1001 vehicle 2g Cream 3 times daily
* Drug: Placebo: 3VM1001 vehicle 3g Cream 3 times daily
* Drug: Placebo: 3VM1001 vehicle 3g Cream 4 times daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthritis of the knee according to American College of Rheumatology clinical radiological criteria. A knee radiograph will be ordered and reviewed. OA of the knee >/= 6 months prior to screening. Subjects with OA of both knees will treat the worst knee. Age 40 years or older Males or females of non-childbearing potential (12 or more months of spontaneous amenorrhea, bilateral oophorectomy at least 6 months prior to randomization, hysterectomy with bilateral oophorectomy at least 6 months prior to randomization, or for females over 50 years of age, hysterectomy without bilateral oophorectomy at least 6 months prior to randomization.; female subjects of childbearing potential must agree to use contraception (abstinence, birth control pills, rings or patches, diaphragm an spermicide, intrauterine device, condom and vaginal spermicide, surgical sterilization, vasectomy, progestin implant or injection); female partners of childbearing potential of male subjects must agree to use contraception as defined above. Moderate to severe OA pain defined a POM score between 40 mm and 90 mm. Baseline WOMAC pain subscale score >/=9. No change in physical activity and/or therapy for the past 3 months. All concurrent medications taken for any reason stable for 14 days Ability to follow protocol with reference to cognitive and situational factors such as stable housing, ability to attend visits. Ability to read and write English. Ability to apply cream without assistance. Able to provide written informed consent Exclusion criteria: Presence of significant medical disorder that would compromise the participant's safety to take part in the study such as cancer, immunosuppressed, or evidence of alcohol or substance abuse. Wilson's disease or other disorder of copper metabolism. BMI >40 Known hypersensitivity or allergy to any component of the product, or to acetaminophen. Transcutaneous electrical nerve stimulation and use of crutches, walkers or wheel chairs should be excluded prior to and during treatment. Use of a cane is permitted. Active conditions over the area to be treated such a eczema or psoriasis, compromised integrity of the intact, superficial skin layer over the area to be treated. Pain in any joint being studied that could interfere with the subject's assessment of pain in the index joint. Recent (within 12 months) injury (traumatic or sports related) to either knee causing pain and interference with daily activities such as walking. Recent (within 12 months) surgery/procedure (including intra-articular injection) to either knee causing pain that could interfere with study assessments of pain, function, and QoL. Extreme pain in the target knee characterized by POM score of </= 40 mm. Mild pain in the target knee characterized by POM score of </= 40 mm. Open surgery of he target knee within the last year. Significant concomitant disease of the knee to be studied such as fracture or osteonecrosis. Arthroscopic surgery of the target knee within the last 3 months. Use of prohibited medications/therapies during he 7-9 day treatment period including: Devices of therapeutics for knee pain or ambulation Analgesics other than acetaminpohen Systemic or locally injected corticosteroids Other investigational drugs Chemotherapy drugs Immunotherapy Topical products applied to he target knee

Ages Eligible for Study
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Minimum Age: 40 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
Interventional Model Description: Double-blind, placebo controlled, randomized
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 3VM1001 2g X 3 daily<br>3VM1001 active cream administered 2g cream three times daily for seven days | Drug: Experimental: 3VM1001 active 2g Cream 3 times daily<br>* 3VM1001 2g Cream with active ingredient administered 3 times daily<br>|
| Placebo Comparator: Placebo; 3VM1001 vehicle 2g X 3 daily<br>3VM1001 placebo vehicle administered 2g cream three times daily for seven days | Drug: Placebo: 3VM1001 vehicle 2g Cream 3 times daily<br>* 3VM1001 placebo 2g vehicle Cream administered 3 times daily<br>|
| Experimental: Experimental 3VM1001 3g X 3 daily<br>3VM1001 active cream administered 3g cream three times daily for seven days | Drug: Experimental: 3VM1001 active 3g Cream 3 times daily<br>* 3VM1001 3g Cream with active ingredient administered 3 times daily<br>|
| Placebo Comparator: Placebo; 3VM1001 vehicle 3g X3 daily<br>3VM1001 placebo vehicle administered 3g cream three times daily for seven day | Drug: Placebo: 3VM1001 vehicle 3g Cream 3 times daily<br>* 3VM1001 placebo 3g vehicle Cream administered 3 times daily<br>|
| Experimental: Experimental 3VM1001 3g x 4 daily<br>3VM1001 active cream administered 3g cream four times daily for seven days | Drug: Experimental: 3VM1001 active 3g Cream 4 times daily<br>* 3VM1001 3g Cream with active ingredient administered 4 times daily<br>|
| Placebo Comparator: Placebo; 3VM1001 vehicle 3g X 4 daily<br>3VM1001 placebo vehicle administered 3g cream four times daily for seven days | Drug: Placebo: 3VM1001 vehicle 3g Cream 4 times daily<br>* 3VM1001 placebo 3g vehicle Cream administered 4 times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time averaged change from baseline in a standard 100 mm Visual Analog Scale (VAS). | The time-averaged mean of all patient pain scores over each study period. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, Serious adverse events, and study discontinuation | Collection of Adverse events, Serious adverse events, and study discontinuation over each study period. | 8 days | 
| Patient global impression of change scale (PGIC) from baseline to end of study period. | This measure is a single-item rating by participants of their improvement with treatment on a 7-point scale that ranges from very much improved to very much worse with a mid-point of no-change. | 8 days | 
| Change in the global rating of disease for 3VM1001 Cream and placebo from baseline to the end of study. | Change in the global rating of disease for 3VM1001 Cream and placebo from baseline to day 8 measured on a 5-point Likert scale, with numerical values recorded by the subjects. | 8 days | 
| Patient Global Impression of change from baseline in Osteoarthritis (OA) pain.. | Subjects will rate their overall satisfaction from baseline (Day 0) to the end of study using a 6-point categorical sale from very much worse(0) to very satisfied (6). | From screening Day 0 to the end of study (8 days) | 
| Change in Patient Global Assessment of Treatment Satisfaction from baseline to end of study. | Subjects will rate their overall satisfaction with study treatment using a 5-point categorical sccale from dissatisfied (0) to very satisfied (4) | 8 days | 
| Use of rescue medication | The use of rescue medication for pain | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, pain, knee