Open Label Safety and Tolerability Study of COV155 in Subjects With Osteoarthritis (OA) or Chronic Low Back Pain (CLBP)

An Open Label Safety Study of COV155 in Subjects With Osteoarthritis or Chronic Low Back Pain

A study to show the safety of COV155 in patients with osteoarthritis of the knee or hip or moderate to severe chronic low back pain.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee; Chronic Low Back Pain; Osteoarthritis, Hip
• Intervention / Treatment: Drug: COV155

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Anaheim, California, United States, 92804
      • United Clinical Research Center, Inc.
    • Anaheim, California, United States, 92801
      • Orange County Research Institute
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Inc.
    • Santa Ana, California, United States, 92701
      • Probe Clinical Research Corporation - Santa Ana
  • Florida
    • Eustis, Florida, United States, 32726
      • Lake Internal Medicine Associates
    • Hialeah, Florida, United States, 33012
      • Palm Springs Research Institute
    • Hialeah, Florida, United States, 33013
      • Eastern Research
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions Inc.
    • Plantation, Florida, United States, 33317
      • Martin E. Hale, MD PA (Gold Coast Research LLC)
    • Port Orange, Florida, United States, 32129
      • Accord Clinical Research, LLC
    • Sanford, Florida, United States, 32771
      • International Clinical Research, LLC
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Beacon Clinical Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • Independent Clinical Researchers
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Clinical Study Center of Asheville, LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates Llc
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Community Research
    • Cincinnati, Ohio, United States, 45255
      • Community Research - Anderson
    • Cincinnati, Ohio, United States, 42542
      • New Horizons Clinical Research
    • Cincinnati, Ohio, United States, 45224
      • Hightop Physicians Inc./Medical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Research Institute
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • DeGarmo Institute for Medical Research
    • North Charleston, South Carolina, United States, 29406
      • Pain Specialists of Charleston
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology, LP
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Plano, Texas, United States, 75023
      • ClinRx Research LLC
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• General good health, other than osteoarthritis (OA) or chronic low back pain (CLBP), based upon results of medical and surgical history and medical exam
• ≥18 years of age
• Voluntarily provide written informed consent

• Female subjects eligible if

  1. Not pregnant or lactating; not planning to become pregnant within next 60 days
  2. Surgically sterile, or 2 years postmenopausal, or practicing acceptable birth control for more than 60 days prior to Screening and use of acceptable birth control during the study and 7 days following the last dose of COV155
• Male subjects biologically capable of having children must use reliable birth control during study and 7 days after the last dose of COV155. Surgical sterilization of the subject's monogamous partner qualifies as adequate birth control

• Clinical diagnosis of one of the following

  1. OA of knee or hip for at least 1 year with moderate to severe daily pain despite chronic use of stable doses of non-steroidal anti-inflammatory drugs (NSAIDs) or other non-steroidal, non-opioid therapies or with therapy including opioids
  2. Moderate to severe CLBP for at least several hours a day for a minimum of 90 days, not due to a known malignancy, and classified as non-neuropathic, neuropathic, or symptomatic for more than 6 months after LBP surgery
  3. OA of knee and scheduled to undergo unilateral primary tricompartmental arthroplasty.
• For CLBP/OA: Average in-clinic pain score of ≥3 on 11-point (0 to 10) numerical rating scale (NRS) as an average for the last 24 hours at Screening; - Pain intensity score of ≥4 on NRS as an average for the last 24 hours at Baseline
• For TKR: 11. Post-operative pain intensity scores ≥ 4 on a 0 to 10 NRS after discontinuation of post-surgical patient controlled analgesia or intravenous pain medications; body mass index ≤ 38.0; classified as either Physical Status (PS)-1 or PS-2.

Exclusion Criteria

• Any clinically significant condition or unstable illness that precludes study participation or interferes with assessment of pain and other symptoms of CLBP or OA or would increase the risk of opioid or NSAID related adverse events
• Schizophrenia or an uncontrolled or poorly controlled major psychiatric condition or clinically significant anxiety or depression
• Active malignancy or history of malignancy within 2 years prior to Screening other than dermal or cervical squamous cell carcinoma in situ
• History of seizures (exception-pediatric febrile seizures)
• Clinically significant ECG abnormalities or uncontrolled hypo- or hypertension
• For CLBP/OA: Arthroscopic or open surgery on either the knee or hip selected as primary OA study joint within 6 months prior to Screening; - For CLBP subjects, a surgical procedure for back pain within 6 months prior to Screening, nerve or plexus block within 30 days prior to Screening or botulinum toxin injection in lower back region within 90 days prior to Screening. For OA subjects, joint injection within 30 days prior to Screening; - Surgical implants of either the knee or hip selected as the primary OA joint; history of spinal stenosis (only CLBP subjects)
• For TKR: Major prior open knee surgery on same side as arthroplasty; any other surgery/elective procedures within 4 weeks of Screening, or during study; going to rehabilitation after surgery
• Gastric reduction or gastric band surgery
• Taking opioids in equivalents to more than 20 mg hydrocodone or more than 40 mg morphine orally per day, or taking opioid medications 4 days a week or more
• Known allergy or hypersensitivity to opioids, acetaminophen or ibuprofen
• Certain lab abnormalities
• Unable to discontinue use of prohibited medications or history of substance or alcohol abuse within 2 years prior to Screening or positive urine drug test at Screening for alcohol, illicit drugs (including medical cannabis) or controlled substances other than prescribed medications
• Positive for human immunodeficiency virus, hepatitis B (surface antigen), and/or hepatitis C
• Any other chronic pain condition other than CLBP or OA that would interfere with the assessment of CLBP or OA
• Used a monoamine oxidase inhibitor, antipsychotic, or benzodiazepine within 14 days prior to Screening or started or changed doses of anticonvulsants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, or tricyclic antidepressants within 30 days prior to Screening
• Previously received COV155 in a study
• Received any investigational drugs or devices within 30 days prior to Screening
• Other criteria as specified in the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: COV155; COV155, loading dose of 3 tablets followed by 2 tablets every 12 hours for 10 to 35 days.	Drug: COV155; COV155 tablets; Other Names: MNK155

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of COV155	Safety evaluations using physical exam, vital signs, clinical laboratory tests, pulse oximetry, and adverse events.	Up to 35 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Brief Pain Inventory short form (mBPI-sf) - intensity	The mean changes from pre-treatment in the worst, least, average, and current pain using the worst, least, average, and current pain intensity items of the mBPI-sf (questions 1 to 4).	Baseline, Weeks 1, 2, 3, 4, and 5
Modified Brief Pain Inventory short form (mBPI-sf) - pain relief	Evaluate pain relief using the pain relief item of the mBPI-sf (question 5).	Baseline, Weeks 1, 2, 3, 4, and 5
Modified Brief Pain Inventory short form (mBPI-sf) - pain interference	Evaluate the pain-related quality of life using the Pain Interference subscale of the mBPI-sf.	Baseline, Weeks 1, 2, 3, 4, and 5
Western Ontario and McMaster Universities Arthritis Index (WOMAC)	The mean changes from pre-treatment in disease-specific quality of life using the WOMAC (48-hour version) for subjects with OA of the hip or knee.	Baseline, Weeks 1, 2, 3, 4, and 5
Roland Morris/Disability Questionnaire	The mean changes from pre-treatment in disease-specific quality of life using the Roland Morris LBP and Disability Questionnaire for subjects with CLBP.	Baseline, Weeks 1, 2, 3, 4, and 5

Collaborators and Investigators

• Sponsor: Mallinckrodt

Publications and helpful links

General Publications

• Zheng Y, Kostenbader K, Barrett T, Hisaw E, Giuliani MJ, Chen Y, Young JL. Tolerability of Biphasic-Release Hydrocodone Bitartrate/Acetaminophen Tablets (MNK-155): A Phase III, Multicenter, Open-Label Study in Patients With Osteoarthritis or Chronic Low Back Pain. Clin Ther. 2015 Jun 1;37(6):1235-47. doi: 10.1016/j.clinthera.2015.03.019. Epub 2015 Apr 23.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: November 5, 2012
• First Submitted That Met QC Criteria: November 6, 2012
• First Posted (ESTIMATE): November 7, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 19, 2016
• Last Update Submitted That Met QC Criteria: October 18, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Back Pain; Low Back Pain; Osteoarthritis, Knee; Osteoarthritis, Hip
• Other Study ID Numbers: COV15010233