A Study to Evaluate the Analgesic Efficacy and Safety of VM902A in Subjects With Osteoarthritis (OA) of the Knee

A Phase 2a, Multicenter, Randomized, Double-blind, Placebo Controlled and Active-controlled, Parallel-group Study Evaluating the Analgesic Efficacy and Safety of VM902A in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee

The purpose of this study is to evaluate the analgesic efficacy, safety, and tolerability of VM902A twice daily compared to placebo in subjects with moderate to severe chronic pain due to OA of the knee.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis Pain of the Knee
• Intervention / Treatment: Drug: VM902A 200-mg Capsules; Drug: Placebo; Drug: VM902A 400-mg Capsules; Drug: Naproxen 500-mg Capsules

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Investigational Site
    • Huntsville, Alabama, United States, 35801
      • Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • Investigational Site
    • Hialeah, Florida, United States, 33012
      • Investigational Site
    • Homestead, Florida, United States, 33030
      • Investigational Site
    • Jupiter, Florida, United States, 33458
      • Investigational Site
    • Orlando, Florida, United States, 32806
      • Investigational Site
    • Port Orange, Florida, United States, 32129
      • Investigational Site
    • Port Saint Lucie, Florida, United States, 34952
      • Investigational Site
    • The Villages, Florida, United States, 32162
      • Investigational Site
    • West Palm Beach, Florida, United States, 33409
      • Investigational Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Investigational Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • Investigational Site
    • Muncie, Indiana, United States, 47304
      • Investigational Site
  • Kansas
    • Newton, Kansas, United States, 67114
      • Investigational Site
    • Prairie Village, Kansas, United States, 66206
      • Investigational Site
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
      • Investigational Site
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Investigational Site
    • Troy, Michigan, United States, 48098
      • Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Investigational Site
    • Saint Louis, Missouri, United States, 63141
      • Investigational Site
  • New York
    • Bronx, New York, United States, 10467
      • Investigational Site
    • Hartsdale, New York, United States, 10530
      • Investigational Site
    • Rosedale, New York, United States, 11422
      • Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Investigational Site
    • Dayton, Ohio, United States, 45417
      • Investigational Site
    • Dublin, Ohio, United States, 43016
      • Investigational Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Investigational Site
  • Utah
    • Ogden, Utah, United States, 84405
      • Investigational Site
    • Salt Lake City, Utah, United States, 84121
      • Investigational Site
    • South Jordan, Utah, United States, 84095
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria Include:

1. Males and females ≥ 40 and ≤ 75 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

2. 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, stiffness < 30 min, 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. Note that K-L grades 2 to 3 require the presence of osteophytes, which is required to meet ACR clinical and radiographic criteria for knee OA

3. 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

4. The subjects must have "average pain over the last 24 hours" scores ≥ 5 and ≤ 9 on an 11-point numerical rating scale (NRS) for the index knee on ≥ 3 consecutive days during the screening period and come in for randomization within 72 hours after qualification is met
5. 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 treatment period, with the exception of study-specific rescue medication.

Key Exclusion Criteria Include:

1. Subjects with radiographic evidence of OA with K-L grade 0, 1, or 4
2. Subjects at risk for destructive arthropathy, subjects with a history of osteonecrosis, osteoporotic fracture, rapidly progressive osteoarthritis (RPOA 1 and 2), subchondral insufficiency fracture, and hip/knee dislocations
3. Subjects considered high risk for surgery based upon American Society of Anesthesiologists physical classification system for surgery grading, or subjects who would not be willing to undergo joint replacement surgery if required
4. Subjects with chronic pain conditions other than OA of the knee as their predominant pain condition, including gout (except for subjects with gout that is controlled with diet and/or with stable suppressive treatment with uric acid reducing medication(s) and/or colchicine, and who have not had any attack within the past 2 years), 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
5. Subjects scheduled for surgical interventions of the disease site or any other major surgery during the study conduct period
6. Subjects with a history of a prior joint replacement of the index knee
7. 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.

Other protocol-specific inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Capsules to match VM902A and/or naproxen taken orally with food twice daily
Experimental: VM902A 200 mg; VM902A 200-mg Capsules	Drug: VM902A 200-mg Capsules; Taken orally with food twice daily; Drug: Placebo; Capsules to match VM902A and/or naproxen taken orally with food twice daily
Experimental: VM902A 400 mg; VM902A 400-mg Capsules (2 x 200-mg capsules)	Drug: Placebo; Capsules to match VM902A and/or naproxen taken orally with food twice daily; Drug: VM902A 400-mg Capsules; Taken orally with food twice daily
Active Comparator: Naproxen; Naproxen 500-mg Capsules	Drug: Placebo; Capsules to match VM902A and/or naproxen taken orally with food twice daily; Drug: Naproxen 500-mg Capsules; Taken orally with food twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Daily "Average Pain Over the Last 24 Hours" Score at Week 4	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly "Average Pain Over the Last 24 Hours" at Week 4		Week 4
Average Daily "Pain Right Now" Score at Week 4		Week 4
Western Ontario and McMaster OA Index (WOMAC) - Total Scores		Week 4
Western Ontario and McMaster OA Index (WOMAC) Pain Severity Subscale Score		Week 4
Western Ontario and McMaster OA Index (WOMAC) Physical Function Subscale Score		Week 4
Western Ontario and McMaster OA Index (WOMAC) Stiffness Subscale Score		Week 4
Modified Brief Pain Inventory-Short Form (mBPI-SF) - Total Scores		Week 4
Modified Brief Pain Inventory-Short Form (mBPI-SF) Pain Severity Subscale Score		Week 4
Modified Brief Pain Inventory-Short Form (mBPI-SF) Pain Interference Subscale Score		Week 4
Medical Outcomes Study 36-item Short-Form Health Survey (SF-36)		Week 4
EuroQol-5D (EQ-5D) to Measure Health Status		Week 4
Patient Global Impression of Change (PGIC) at the End of the Double-blind Period		Week 4
Supplemental Analgesic Medication Use	The average daily number of tablets of supplemental pain medication taken during the study.	Days 1 - 28
Responder to Treatment	The percentage reduction from the baseline mean "average pain over the last 24 hours" score to the week 4 mean pain score from the mBPI-SF pain severity subscale.	Week 4
Hospital Anxiety and Depression Scale (HADS) Score	Safety assessment to evaluate the impact of VM902A on mood (anxiety and depression)	Baseline to Week 4
Columbia-Suicide Severity Rating Score (C-SSRS)	Safety assessment to evaluate the occurrence of treatment-emergent suicidal ideation	Baseline to Week 4
Survey of Autonomic Symptoms (SAS) Score	Safety assessment to evaluate symptoms of autonomic dysfunction	Baseline to Week 4
Kellgren-Lawrence Classification (K-L) Score	Safety assessment to classify the severity of knee OA	Baseline to Week 4

Collaborators and Investigators

• Sponsor: Purdue Pharma LP

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): November 22, 2016
• Study Completion (Actual): November 22, 2016

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimate): July 28, 2016

Study Record Updates

• Last Update Posted (Actual): November 22, 2017
• Last Update Submitted That Met QC Criteria: November 20, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Osteoarthritis; Pain; Osteoarthritis, knee
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: TKA2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No