Clinical trial NCT01722864: Open Label Safety and Tolerability Study of COV155 in Subjects With Osteoarthritis (OA) or Chronic Low Back Pain (CLBP)
Official title: An Open Label Safety Study of COV155 in Subjects With Osteoarthritis or Chronic Low Back Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Chronic Low Back Pain
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2012-11-07
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety and tolerability of COV155
timeFrame: Up to 35 days
Secondary outcomes:
measure: Modified Brief Pain Inventory short form (mBPI-sf) - intensity
timeFrame: Baseline, Weeks 1, 2, 3, 4, and 5
measure: Modified Brief Pain Inventory short form (mBPI-sf) - pain relief
timeFrame: Baseline, Weeks 1, 2, 3, 4, and 5
measure: Modified Brief Pain Inventory short form (mBPI-sf) - pain interference
timeFrame: Baseline, Weeks 1, 2, 3, 4, and 5
measure: Western Ontario and McMaster Universities Arthritis Index (WOMAC)
timeFrame: Baseline, Weeks 1, 2, 3, 4, and 5
measure: Roland Morris/Disability Questionnaire
timeFrame: Baseline, Weeks 1, 2, 3, 4, and 5
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials
state: California
city: Anaheim
country: United States
facility: Orange County Research Institute
state: California
city: Anaheim
country: United States
facility: United Clinical Research Center, Inc.
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Inc.
state: California
city: Santa Ana
country: United States
facility: Probe Clinical Research Corporation - Santa Ana
state: California
city: Eustis
country: United States
facility: Lake Internal Medicine Associates
state: Florida
city: Hialeah
country: United States
facility: Palm Springs Research Institute
state: Florida
city: Hialeah
country: United States
facility: Eastern Research
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Plantation
country: United States
facility: Martin E. Hale, MD PA (Gold Coast Research LLC)
state: Florida
city: Port Orange
country: United States
facility: Accord Clinical Research, LLC
state: Florida
city: Sanford
country: United States
facility: International Clinical Research, LLC
state: Florida
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research
state: Indiana
city: Brockton
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Las Vegas
country: United States
facility: Independent Clinical Researchers
state: Nevada
city: Asheville
country: United States
facility: Clinical Study Center of Asheville, LLC
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: The Center for Clinical Research LLC
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Cincinnati
country: United States
facility: Hightop Physicians Inc./Medical Research Center
state: Ohio
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Cincinnati
country: United States
facility: Community Research - Anderson
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Greer
country: United States
facility: DeGarmo Institute for Medical Research
state: South Carolina
city: North Charleston
country: United States
facility: Pain Specialists of Charleston
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Austin
country: United States
facility: FutureSearch Trials of Neurology, LP
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Plano
country: United States
facility: ClinRx Research LLC
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC
state: Virginia
Study officials:
References:
citation: 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.