A Study to Evaluate the Analgesic Efficacy and Safety of V120083 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 V120083 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 of V120083 twice daily compared to placebo in subjects with moderate to severe chronic pain due to OA of the knee.

Study Overview

• Status: Completed
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Drug: V120083; Drug: Placebo; Drug: Naproxen

• Study Type: Interventional
• Enrollment (Actual): 291
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics, LLC
    • Tuscumbia, Alabama, United States, 35674
      • Terence T. Hart, MD
  • California
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • San Marcos, California, United States, 92078
      • Artemis Institute for Clinical Research
  • Florida
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Miami, Florida, United States, 33165
      • Future Care Solution, LLC
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare, LLC
    • Orlando, Florida, United States, 32810
      • Omega Research Consultants, LLC
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Buynak Clinical Research, P.C.
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
    • Saint Louis, Missouri, United States, 63128
      • St. Louis Center for Clinical Research
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Clinical Trials, LC
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Hartsdale, New York, United States, 10530
      • Drug Trials America
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Medication Management, LLC
    • Mooresville, North Carolina, United States, 28117
      • Research Institute of the Carolinas of Piedmont Healthcare, PA
    • Morganton, North Carolina, United States, 28655
      • Burke Primary Care
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
    • Dayton, Ohio, United States, 45439
      • Providence Health Partners - Center For Clinical Research
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Mountain View Clinical Research, Inc.
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria Include:

1. 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

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, 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.

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 ≥ 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
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 study, 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 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
3. Subjects scheduled for surgical interventions of the disease site or any other major surgery during the study conduct period
4. Subjects with a history of a prior joint replacement of the index knee
5. 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
6. Subjects with a history of significant trauma to a knee, hip or shoulder within the previous year
7. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: V120083 30 mg; V120083 30-mg capsules taken orally twice daily	Drug: V120083; Capsules; Drug: Placebo; Capsules to match V120083 and/or naproxen
EXPERIMENTAL: V120083 60 mg; V120083 60-mg (2 x 30 mg) capsules taken orally twice daily	Drug: V120083; Capsules; Drug: Placebo; Capsules to match V120083 and/or naproxen
ACTIVE_COMPARATOR: Naproxen; Naproxen 500-mg capsules taken orally twice daily	Drug: Placebo; Capsules to match V120083 and/or naproxen; Drug: Naproxen; Capsules
PLACEBO_COMPARATOR: Placebo; Capsules to match V120083 and/or naproxen taken orally twice daily	Drug: Placebo; Capsules to match V120083 and/or naproxen

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Purdue Pharma LP
• Collaborators: Shionogi

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 14, 2017
• Primary Completion (ACTUAL): November 10, 2017
• Study Completion (ACTUAL): November 21, 2017

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: January 19, 2017
• First Posted (ESTIMATE): January 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2019
• Last Update Submitted That Met QC Criteria: January 25, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Osteoarthritis; Pain; Osteoarthritis Knee
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; 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: VAN2001

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No