A Study to Evaluate the Analgesic Efficacy and Safety of V120083 in Subjects With Osteoarthritis (OA) of the Knee

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the analgesic efficacy of V120083 twice daily compared to placebo in subjects with moderate to severe chronic pain due to OA of the knee.

Official Title
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A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled and Active-controlled, Parallel-group Study Evaluating the Analgesic Efficacy and Safety of V120083 in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee

Conditions
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Osteo Arthritis Knee

Intervention / Treatment
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* Drug: V120083
* Drug: Naproxen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Include: Males and females ≥ 40 and ≤ 80 years of age with moderate to severe chronic OA pain of the knee (lasting several hours daily) as their predominant pain condition for at least 6 months prior to screening Diagnostic criteria for primary pain condition (American College of Rheumatology [ACR] clinical and radiographic criteria): At least 1 of the following in addition to knee pain: age > 50, morning stiffness < 30 minutes, crepitus on active motion, and Kellgren-Lawrence (K-L) grade 2 or 3 radiographic evidence at the screening visit as determined by a local radiologist or rheumatologist. If a radiograph is not available, one must be taken and the diagnostic criteria must be confirmed before randomization. Subjects whose OA pain of the index knee is not adequately treated prior to the screening visit: Subjects must have a self-reported average pain intensity rating of moderate or severe on a verbal rating scale (ie, none, mild, moderate, and severe) over the 7 days prior to the screening visit The subjects must have average pain over the last 24 hours scores ≥ 4 and ≤ 9 on an 11-point numerical rating scale (NRS) for the index knee on ≥ 3 consecutive days during the pain assessment period and come in for randomization within 96 hours after the latest qualifying pain score entry Subjects who are willing and able to stop taking any/all analgesic medications, including over-the-counter pain medications, opioids, marijuana, and topical analgesics for OA pain for the duration of the study, with the exception of study-specific rescue medication. Key Exclusion Criteria Include: Subjects with radiographic evidence of OA with K-L grade 0,1 or 4 Subjects with chronic pain conditions other than OA of the knee as their predominant pain condition, including gout, pseudogout, psoriatic arthritis, active Lyme disease, rheumatoid arthritis or any other inflammatory arthritis, fibromyalgia, neuropathic pain conditions, bursitis, or acute injury or signs of active infection in the target pain area Subjects scheduled for surgical interventions of the disease site or any other major surgery during the study conduct period Subjects with a history of a prior joint replacement of the index knee Subjects who have had arthroscopy on either knee or hip within 6 months of entering the study, or open surgery on either knee or hip within 12 months of entering the study Subjects with a history of significant trauma to a knee, hip or shoulder within the previous year Subjects who have significant pain, other than or more than knee pain, including significant hip, back pain, that may confound the analgesic efficacy assessments of this study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V120083 30 mg<br>V120083 30-mg capsules taken orally twice daily | Drug: V120083<br>* Capsules<br>Drug: Placebo<br>* Capsules to match V120083 and/or naproxen<br>|
| Experimental: V120083 60 mg<br>V120083 60-mg (2 x 30 mg) capsules taken orally twice daily | Drug: V120083<br>* Capsules<br>Drug: Placebo<br>* Capsules to match V120083 and/or naproxen<br>|
| Active Comparator: Naproxen<br>Naproxen 500-mg capsules taken orally twice daily | Drug: Naproxen<br>* Capsules<br>Drug: Placebo<br>* Capsules to match V120083 and/or naproxen<br>|
| Placebo Comparator: Placebo<br>Capsules to match V120083 and/or naproxen taken orally twice daily | Drug: Placebo<br>* Capsules to match V120083 and/or naproxen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Average Pain Over the Last 24 Hours Score at Week 4 | At week 4, subjects were asked to rate their pain on an 11-point numerical scale where 0 = no pain, 10 = pain as bad as you can imagine. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Change From Baseline Score of Average Pain Over the Last 24 Hours From the mBPI-SF Pain Severity Subscale | Subjects were asked to rate their pain on an 11-point numerical scale where 0 = no pain, 10 = pain as bad as you can imagine. | Weeks 1, 2 and 4 | 
| Average Daily Pain Right Now Score Collected by e-Diary | Subjects were asked to rate their pain on an 11-point numerical scale where 0 = no pain, 10 = pain as bad as you can imagine. | 4 Weeks | 
| Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Pain Subscale | The pain subscale consisted of 5 items: walking; stair climbing; nocturnal; at rest; weight bearing. The score for each item ranged from 0 (none) to 4 (extreme). The pain subscale score was obtained by adding the responses to the 5 items which could range from 0 to 20. | 4 Weeks | 
| Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Stiffness Subscale | The stiffness subscale consisted of 2 items; morning stiffness and stiffness occurring later in the day. The score for each item ranged from 0 (none) to 4 (extreme) and the stiffness subscale score was obtained by adding the responses to the 2 items which could range from 0 - 8. | 4 Weeks | 
| Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Physical Function Subscale | The physical function subscale consisted of 17 items: descending stairs; ascending stairs; rising from sitting; standing; bending to floor; walking on flat surface; getting into or out of car; going shopping; putting on socks; rising from bed; taking off socks; lying in bed; sitting; getting into or out of the bathtub; getting on or off the toilet; heavy domestic duties; light domestic duties. The score for each item ranged from 0 (none) to 4 (extreme) and the physical function subscale score was obtained by adding the responses to the 17 items which could range from 0 to 68. | 4 Weeks | 
| Western Ontario and McMaster Osteoarthritis Index (WOMAC) - Total Score | The total score of the WOMAC consisted of 24 items (5 items from the pain subscale, 2 items from the stiffness subscale, and 17 items from the physical function subscale). The total score was obtained by adding the scores from these 3 subscales and could range from 0 to 96. | 4 Weeks | 
| Modified Brief Pain Inventory-Short Form (mBPI-SF) - Total Score (All Parts of 6 Questions) | The mBPI-SF consists of 6 questions and is a self-administered questionnaire used to assess the severity of pain, and the interference of pain on daily functions. Subjects rated their severity of pain / interference of pain on a 0 (no pain / does not interfere) to 10 (as bad as you can imagine / completely interferes) numerical rating scale (NRS) The total score is the sum of all parts of the 6 questions and the total score range is 0 - 110. | 4 Weeks | 
| Modified Brief Pain Inventory-Short Form (mBPI-SF) Pain Severity Subscale Score | The mBPI-SF is a self-administered questionnaire. The pain severity subscale of the mBPI-SF consists of 4 questions which ask the subjects to rate their severity of pain on a 0 to 10 NRS for worst pain, least pain, average pain, and current pain. The severity of pain was computed as the mean of questions 1-4. The mean severity of pain scores could range from 0 to 10. | 4 Weeks | 
| Modified Brief Pain Inventory-Short Form (mBPI-SF) Pain Interference Subscale Score | The mBPI-SF is a self-administered questionnaire. The pain interference subscale of the mBPI-SF consists of Question 6 which has 7 parts, all of which ask the subjects to rate the impact/interference of their pain on various functions, ie, general activity, mood, walking, normal work, relations with others, sleep, and enjoyment of life on a 0 to 10 NRS where 0 = does not interfere and 10 = completely interferes. The mean interference of pain scores could range from 0 to 10. | 4 Weeks | 
| Responder to Treatment (Calculated as the Percentage Reduction of Average Pain Over the Last 24 Hours) at Week 4 | A subject's response to treatment was defined as the percentage reduction from the baseline average pain over the last 24 hours score to the week 4 pain score from the mBPI-SF pain severity subscale. Responders were defined as having > 0 % reduction; non-responders were defined as having ≤ 0% reduction. | Week 4 | 
| Medical Outcomes Study Short Form-36 (SF-36) - Physical Component Summary | The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the subject's perspective. The survey is summarized into 8 dimensions/scales: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). The Physical Component Summary is derived from 4 of the 8 health dimensions (aggregate of PF, RP, BP, and GH scales). The minimum score is 0 and the maximum score is 100. A higher score indicates a better health state. | 4 Weeks | 
| Medical Outcomes Study Short Form-36 (SF-36) - Mental Component Summary | The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the subject's perspective. The survey is summarized into 8 dimensions/scales: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). The Mental Component Summary is derived from 4 of the 8 health dimensions,(aggregate of VT, SF, RE, and MH scales). The minimum score is 0 and the maximum score is 100. A higher score indicates a better health state. | 4 Weeks | 
| European Quality of Life Scale - 5 Dimensions (EQ-5D-5L) to Measure Health Status | EQ-5D-5L is a standardized generic measure of health status for clinical and economic appraisal based on a descriptive system that defines health in terms of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It includes a visual analogue scale (VAS) with scores ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). | 4 Weeks | 
| Patient Global Impression of Change (PGIC) | The PGIC is an ordinal scale which assesses the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse), where 1 = very much improved and 7 = very much worse. The number of subjects responding very much improved and much improved was summarized by treatment group. | 4 Weeks | 
| Supplemental Analgesic Medication Use | The average daily number of tablets of supplemental pain medication used during the double-blind period was summarized by treatment group. | Up to 28 days | 
| Number of Participants With Treatment-emergent Suicidal Ideation and Behaviors Assessed by Columbia-Suicide Severity Rating Score (C-SSRS) | Suicidality was monitored throughout the study using the C-SSRS. The C-SSRS involves a series of probing questions to inquire about possible suicidal thinking and behavior. The composite endpoints (Suicidal Ideation, Suicidal Behavior, Suicidal Ideation or Behavior) included subjects who experienced any one of the events at least once during treatment. | Baseline up to 4 Weeks | 
| Change From Baseline to Week 4 in Hospital Anxiety and Depression Scale (HADS) Score | Safety assessment to evaluate the impact of V120083 on mood (anxiety [HADS-A] and depression [HADS-D]). The score for each subscale ranges from 0 (no anxiety or depression) to 21, with a score of 11 or higher indicating the probable presence of the mood disorder. | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Pain, Osteoarthritis Knee