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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01451385

Enrollment

376

Registered

2011-10-13

Start date

2011-09-20

Completion date

2012-06-18

Last updated

2020-09-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Low Back Pain, Osteoarthritis

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).

Interventions

DRUGCOV795

COV795 is a multilayer extended-release tablet for oral administration of oxycodone hydrochloride (15 mg) and acetaminophen (650 mg)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Inclusion 1. Be considered in general good health based upon medical and surgical history, vital signs, pulse oximetry, physical exam, clinical lab tests, and electrocardiogram (ECG). 2. Be ≥18 years of age 3. 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 4. 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 5. 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 6. 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. 7. Have a pain intensity score of ≥4 on NRS as an average for the last 24 hours at baseline visit. 8. Must, in the investigator's opinion, qualify for opioid therapy for their CLBP or OA. 9. Voluntarily provide written informed consent. Exclusion 1. 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 2. Have an uncontrolled or poorly controlled major psychiatric condition, or have clinically significant anxiety or depression 3. Have an active malignancy or history of malignancy within 2 years 4. Have a history of seizures (except pediatric febrile seizures) or cognitive dysfunction 5. Have clinically significant ECG abnormalities or have uncontrolled hypo- or hypertension 6. Had arthroscopic or open surgery on either knee or hip selected as the primary OA study joint within 6 months 7. For CLBP, had a surgical procedure for back pain within 6 months 8. 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. 9. Had surgical implants of either the knee or hip selected as the primary OA joint 10. Had gastric reduction surgery 11. 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 12. Unable to discontinue use of prohibited medications 13. Have a known allergy or hypersensitivity to opioids, OC, acetaminophen (APAP) or ibuprofen. 14. Have abnormal clinical laboratory tests at screening 15. Have a history of substance or alcohol abuse 16. Have positive screening labs for human immunodeficiency virus (HIV), Hepatitis B and/or Hepatitis C 17. Have a positive urine drug test for alcohol, illicit drugs, or controlled substances other than those prescribed medications 18. Have previously participated in a clinical trial using COV795 19. Received any investigational drugs or devices in the past 4 weeks 20. History of spinal stenosis 21. Other criteria as specified in the trial protocol

Design outcomes

Primary

Measure	Time frame	Description
Summary of Adverse Events (AEs)	5 Weeks	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).

Secondary

Measure	Time frame	Description
Modified Brief Pain Index - Short Form: Percent Pain Relief From Medication	at end of treatment (within 5 weeks)	Participants rate percent pain relief from medication on a scale from 0% (no relief) to 100% (complete relief)
Modified Brief Pain Inventory-Short Form: Pain Interference Scores	at end of treatment (within 5 weeks)	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.
Western Ontario and McMaster Universities Arthritis Index (WOMAC) Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Pain Score	End of treatment (within 5 weeks)	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.
Modified Brief Pain Index - Short Form: Pain Intensity	at end of treatment (within 5 weeks)	Participants rate their pain on a score from 0=no pain to 10=pain as bad as you can imagine
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Physical Function Score	End of treatment (within 5 weeks)	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.
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Total Score	End of treatment (within 5 weeks)	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.
Roland-Morris Low Back Pain and Disability Scores for Participants With Chronic Low Back Pain	End of treatment (within 5 weeks)	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.
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Stiffness Score	End of treatment (within 5 weeks)	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.

Countries

United States

Participant flow

Pre-assignment details

After a screening period of up to 14 days, enrolled participants began treatment

Participants by arm

Arm	Count
All Participants All participants receive 2 tablets of COV795 every 12 hours for up to 35 days	376
Total	376

Baseline characteristics

Characteristic	All Participants
Age, Continuous	52.2 years STANDARD_DEVIATION 13.72
Ethnicity (NIH/OMB) Hispanic or Latino	58 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	318 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Modified Brief Pain Index - Short Form: Pain Intensity Average pain in the last 24 hours	6.7 score on a scale STANDARD_DEVIATION 1.38
Modified Brief Pain Index - Short Form: Pain Intensity Least pain in last 24 hours	5.6 score on a scale STANDARD_DEVIATION 1.94
Modified Brief Pain Index - Short Form: Pain Intensity Pain right now	6.7 score on a scale STANDARD_DEVIATION 1.64
Modified Brief Pain Index - Short Form: Pain Intensity Worst pain in last 24 hours	7.6 score on a scale STANDARD_DEVIATION 1.32
Modified Brief Pain Inventory-Short Form: Pain Interference Scores	5.4 score on a scale STANDARD_DEVIATION 2.03
Modified Brief Pain Inventory-Short Form: Percent Pain Relief from Medication	13.2 percentage pain relief from medication STANDARD_DEVIATION 21.93
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	62 Participants
Race (NIH/OMB) Black or African American	75 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	237 Participants
Roland-Morris Low Back Pain and Disability Scores for Participants with Chronic Low Back Pain	10.9 score on a scale STANDARD_DEVIATION 5.27
Sex: Female, Male Female	220 Participants
Sex: Female, Male Male	156 Participants
Western Ontario and McMaster U. Scores for Participants With Osteoarthritis (OA) of the Hip or Knee	11.74 score on a scale STANDARD_DEVIATION 2.971
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Physical Function	38.96 score on a scale STANDARD_DEVIATION 9.863
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Stiffness Score	4.94 score on a scale STANDARD_DEVIATION 1.254
WOMAC Questionnaire for Participants With Osteoarthritis (OA) of the Hip or Knee: Total Score	55.63 score on a scale STANDARD_DEVIATION 13.251

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	2 / 376
other Total, other adverse events	235 / 376
serious Total, serious adverse events	4 / 376

Outcome results

Primary

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).

Time frame: 5 Weeks

Population: All participants = safety population

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
All Participants	Summary of Adverse Events (AEs)	Had any TEAE	235 Participants
All Participants	Summary of Adverse Events (AEs)	Had a Severe TEAE	17 Participants
All Participants	Summary of Adverse Events (AEs)	Had a TEAE related to study medication	200 Participants
All Participants	Summary of Adverse Events (AEs)	Had a Serious AE	4 Participants
All Participants	Summary of Adverse Events (AEs)	Died	2 Participants
All Participants	Summary of Adverse Events (AEs)	Had a TEAE leading to discontinuation	73 Participants

Secondary

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

Time frame: at end of treatment (within 5 weeks)

Population: All participants = safety population with a score at end of treatment (week 5)

Arm	Measure	Group	Value (MEAN)	Dispersion
All Participants	Modified Brief Pain Index - Short Form: Pain Intensity	Worst pain in the last 24 hours	4.0 score on a scale	Standard Deviation 2.58
All Participants	Modified Brief Pain Index - Short Form: Pain Intensity	Least pain in last 24 hours	2.4 score on a scale	Standard Deviation 2.13
All Participants	Modified Brief Pain Index - Short Form: Pain Intensity	Average pain in the last 24 hours	3.2 score on a scale	Standard Deviation 2.25
All Participants	Modified Brief Pain Index - Short Form: Pain Intensity	Pain right now	2.8 score on a scale	Standard Deviation 2.36

Secondary

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)

Time frame: at end of treatment (within 5 weeks)

Population: Safety population with a score at end of treatment

Arm	Measure	Value (MEAN)	Dispersion
All Participants	Modified Brief Pain Index - Short Form: Percent Pain Relief From Medication	67.7 percentage of relief from medication	Standard Deviation 28.47

Secondary

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.

Time frame: at end of treatment (within 5 weeks)

Population: Safety population with a score at end of treatment

Arm	Measure	Value (MEAN)	Dispersion
All Participants	Modified Brief Pain Inventory-Short Form: Pain Interference Scores	2.2 score on a scale	Standard Deviation 2.22

Secondary

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.