Study of COV795 in Subjects With Osteoarthritis or Chronic Low Back Pain

Study Overview
=================
Brief Summary
-----------------
The primary objective is to demonstrate the safety and tolerability of COV795 with up to 35 days use as evaluated by physical exam, vital signs, pulse oximetry, clinical laboratory tests, and other adverse events (AEs).

Official Title
-----------------
An Open Label Safety Study of COV795 in Subjects With Osteoarthritis or Chronic Low Back Pain

Conditions
-----------------
Osteoarthritis, Low Back Pain

Intervention / Treatment
-----------------
* Drug: COV795


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Be considered in general good health based upon medical and surgical history, vital signs, pulse oximetry, physical exam, clinical lab tests, and electrocardiogram (ECG). Be ≥18 years of age Female subjects are eligible if not pregnant, not lactating or not planning to become pregnant within the next 2 months; surgically sterile or at least 2 years postmenopausal, or practicing an acceptable form of birth control for the duration of the study Male subjects biologically capable of having children must agree to the use of a reliable method of birth control for the duration of the study Have a clinical diagnosis of one of the following: Osteoarthritis (OA) of the knee or hip for at least one year based on the American College of Rheumatology (ACR) criteria Moderate to severe chronic lower back pain (CLBP), i.e. pain that occurs in an area with boundaries between the lowest rib and the crease of the buttocks that 1) must have been present for at least several hours a day for a minimum of 3 months, 2) is not due to a known malignancy, and 3) must be classified as non-neuropathic, neuropathic, or symptomatic for more than 6 months after lower back pain (LBP) surgery based on the Quebec Task Force Classification of Spinal Disorders Have an average in-clinic pain score of ≥3 on the 11-point (0-10) numerical rating scale (NRS) as an average for the last 24 hours at screening visit. Have a pain intensity score of ≥4 on NRS as an average for the last 24 hours at baseline visit. Must, in the investigator's opinion, qualify for opioid therapy for their CLBP or OA. Voluntarily provide written informed consent. Exclusion Have any clinically significant condition or unstable inter-current illness that would preclude study participation or interfere with the assessment of pain and other symptoms of CLBP or OA or would increase the risk of opioid-related AEs Have an uncontrolled or poorly controlled major psychiatric condition, or have clinically significant anxiety or depression Have an active malignancy or history of malignancy within 2 years Have a history of seizures (except pediatric febrile seizures) or cognitive dysfunction Have clinically significant ECG abnormalities or have uncontrolled hypo- or hypertension Had arthroscopic or open surgery on either knee or hip selected as the primary OA study joint within 6 months For CLBP, had a surgical procedure for back pain within 6 months For CLBP participants, had a nerve or plexus block within 1 month or botulinum toxin injection in the lower back region within 3 months. For participants with OA of the selected primary joint, had joint injection within 1 month prior to Screening Visit 1. Had surgical implants of either the knee or hip selected as the primary OA joint Had gastric reduction surgery Have been taking opioids in equivalents to more than 20 mg oxycodone hydrochloride (OC) or more than 40 mg morphine sulfate (MS) orally per day, or have been taking opioid medications 4 times a week or more Unable to discontinue use of prohibited medications Have a known allergy or hypersensitivity to opioids, OC, acetaminophen (APAP) or ibuprofen. Have abnormal clinical laboratory tests at screening Have a history of substance or alcohol abuse Have positive screening labs for human immunodeficiency virus (HIV), Hepatitis B and/or Hepatitis C Have a positive urine drug test for alcohol, illicit drugs, or controlled substances other than those prescribed medications Have previously participated in a clinical trial using COV795 Received any investigational drugs or devices in the past 4 weeks History of spinal stenosis Other criteria as specified in the trial protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COV795<br>Participants receive 2 tablets of COV795 every 12 hours for up to 35 days | Drug: COV795<br>* COV795 is a multilayer extended-release tablet for oral administration of oxycodone hydrochloride (15 mg) and acetaminophen (650 mg)<br>* Other names: MNK795;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Adverse Events (AEs) | Collection of AEs began with subject's signing of the informed consent form, continued throughout the trial, and ended 7 days following the last dose of study drug, or at early termination. Treatment emergent AEs (TEAEs) are AEs that occurred after the first dose of study drug. TEAEs leading to discontinuation include 2 subjects who died (deaths not related to study drug). Clinically significant changes in values from physical exam, vital signs, clinical laboratory tests, and pulse oximetry were included as treatment emergent adverse events (TEAEs). | 5 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Brief Pain Index - Short Form: Pain Intensity | Participants rate their pain on a score from 0=no pain to 10=pain as bad as you can imagine | at end of treatment (within 5 weeks) | 
| Modified Brief Pain Index - Short Form: Percent Pain Relief From Medication | Participants rate percent pain relief from medication on a scale from 0% (no relief) to 100% (complete relief) | at end of treatment (within 5 weeks) | 
| Modified Brief Pain Inventory-Short Form: Pain Interference Scores | Participants answer several questions about how much the pain interferes with their quality of life. The answers range from 0 = no interference to 10=completely interferes, and the average score for all the questions is recorded. | at end of treatment (within 5 weeks) | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Pain Score | Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC pain score ranges from 0 to 20, with higher scores representing worse pain. | End of treatment (within 5 weeks) | 
| WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Stiffness Score | Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC stiffness score ranges from 0 to 8, with higher scores representing worse stiffness. | End of treatment (within 5 weeks) | 
| WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Physical Function Score | Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC physical function score ranges from 0 to 68, with higher scores representing worse functional limitations. | End of treatment (within 5 weeks) | 
| WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Total Score | Disease-specific quality of life is assessed using the WOMAC questionnaire (48-hour version) for participants with osteoarthritis (OA) of the hip or knee. The WOMAC total score ranges from 0 to 96, with higher scores representing worse pain/disability. | End of treatment (within 5 weeks) | 
| Roland-Morris Low Back Pain and Disability Scores for Participants With Chronic Low Back Pain | Roland-Morris Low Back Pain and Disability Scores for participants with chronic low back pain range from 0 to 24, with higher scores representing greater disability. | End of treatment (within 5 weeks) |