Title

Oxycodone DETERx™ Versus Placebo in Chronic Low Back Pain (CLBP)
A Phase 3, Multi-Center, Randomized, Double-blind, Placebo-Controlled, Safety, Tolerability, and Efficacy Study of Oxycodone DETERx™ Versus Placebo in Opioid-Experienced and Opioid-Naive Subjects With Moderate-to-Severe Chronic Low Back Pain
  • Phase

    Phase 3
  • Study Type

    Interventional
  • Intervention/Treatment

    oxycodone ...
  • Study Participants

    740
The purpose of this study is to evaluate the analgesic efficacy of Oxycodone DETERx compared with placebo in opioid-experienced and opioid-naive subjects with moderate-to-severe chronic low back pain requiring around-the-clock opioid analgesia for an extended period of time.
Study Started
Aug 31
2012
Primary Completion
Jun 30
2014
Study Completion
Jul 31
2014
Results Posted
Feb 23
2017
Last Update
Oct 19
2020

Drug Oxycodone DETERx

40-160 mg total daily dose of oxycodone DETERx, divided into 2 doses, q12h

Drug Placebo

Placebo, divided into 2 doses, q12h

Oxycodone DETERx Experimental

Placebo Placebo Comparator

Criteria

Inclusion Criteria:

Male or non-pregnant female 18-75 years of age (inclusive) at the time of consent.
Must have a clinical diagnosis of moderate-to-severe CLBP for a minimum of 6 months prior to screening.
Must qualify for ATC opioid therapy for treatment of CLBP.
Must be classified as non-malignant and non-neuropathic (Class 1 and 2), neuropathic (Class 3), or symptomatic for more than 6 months after low back pain surgery (Class 9) based on the Quebec Task Force Scale score.
Female subjects of childbearing potential will use an acceptable method of birth control.
Must be in general good health based on screening physical examination.
Must be willing and able to comply with all study procedures and visit requirements.

Exclusion Criteria:

Known to be refractory or intolerant to the analgesic effects of opioids or have failed previous opioid therapy.
A medical condition that would compromise the subject's ability to swallow, absorb, metabolize, or excrete the study drug, including (but not limited to) intractable nausea and/or vomiting and/or severe gastrointestinal narrowing (pathologic or iatrogenic), bowel obstruction, ileostomy, colostomy, or is suspected of having paralytic ileus.
A surgical procedure for back pain within 6 months prior to the Screening Visit.
Any other chronic pain condition other than CLBP that would interfere with the assessment of CLBP (e.g., osteoarthritis, rheumatoid arthritis, post-herpetic neuralgia, pain associated with diabetic neuropathy, fibromyalgia, migraine headaches requiring opioid therapy).
Known history of major depressive disorder that is not controlled with medication or has other conditions that produce significant cognitive or emotional disability.
Any clinically significant unstable medical abnormality or acute or chronic disease of the cardiovascular, gastrointestinal, respiratory (e.g., chronic obstructive pulmonary disease), hepatic, or renal systems.
Known history of alcohol and/or drug abuse.
Positive urine drug screen for illegal or non-prescribed drugs
Known history of seizure disorder, epilepsy, convulsions, or increased intracranial pressure anytime during the subject's life except pediatric febrile seizures.
Known history of head injury within 6 months of Screening Visit.
Current malignancy or a history within past 2 years of malignancy, with the exception of basal cell carcinoma or cervical carcinoma in situ that have been successfully treated.
Positive for human immunodeficiency virus (HIV) or hepatitis B surface antigen, or hepatitis C antibody
Subject is not able or is unwilling to meet the study attendance requirements.

Other protocol specific inclusion and exclusion criteria may apply.

Summary

Screening

Oxycodone DETERx (Titration Phase)

Oxycodone DETERx (Double-blind Maintenance Phase)

Placebo (Double-blind Maintenance Phase)

All Events

Event Type Organ System Event Term Screening Oxycodone DETERx (Titration Phase) Oxycodone DETERx (Double-blind Maintenance Phase) Placebo (Double-blind Maintenance Phase)

Change in Average Pain Intensity Measured by the Change in Pain Intensity-Numeric Rating Scale (PI-NRS) Scores From Randomization Baseline to Week 12 of the Double-blind Maintenance Phase

The PI-NRS is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain).

Oxycodone DETERx (Double-blind Maintenance Phase)

0.29
units on a scale (Mean)
Standard Error: 0.146

Placebo (Double-blind Maintenance Phase)

1.85
units on a scale (Mean)
Standard Error: 0.223

Time-to-exit From the Study for All Causes

Survival analysis. Measure type indicated as 'Number' below represents 25% quartile, given that the median was not reached. These data are consistent with subject completion in the Participant Flow module.

Oxycodone DETERx (Double-blind Maintenance Phase)

58.0
Days
95% Confidence Interval: 37.0 to 78.0

Placebo (Double-blind Maintenance Phase)

35.0
Days
95% Confidence Interval: 29.0 to 38.0

Percent Reduction in Pain Intensity for Responders

Includes the cumulative distribution of subjects with an improvement in pain intensity, as measured on an 11-point PI-NRS scale, and the proportion of responders with at least 30% and at least 50% reduction in pain intensity.

Oxycodone DETERx (Double-blind Maintenance Phase)

Subjects with 30% Improvement

95.0
participants

Subjects with 50% Improvement

74.0
participants

Placebo (Double-blind Maintenance Phase)

Subjects with 30% Improvement

65.0
participants

Subjects with 50% Improvement

48.0
participants

Weekly Changes in Pain Intensity

Weekly pain intensity scores were calculated based on averaged daily pain intensity scores (PI-NRS). Increases to the weekly change in pain intensity, correspond to increases in the PI-NRS scores (i.e. more pain).

Oxycodone DETERx (Double-blind Maintenance Phase)

Week 1

0.1
units on a scale (Mean)
Standard Deviation: 0.85

Week 10

0.2
units on a scale (Mean)
Standard Deviation: 1.55

Week 11

0.2
units on a scale (Mean)
Standard Deviation: 1.62

Week 12

0.3
units on a scale (Mean)
Standard Deviation: 1.54

Week 2

Week 3

0.1
units on a scale (Mean)
Standard Deviation: 1.14

Week 4

0.1
units on a scale (Mean)
Standard Deviation: 1.25

Week 5

0.2
units on a scale (Mean)
Standard Deviation: 1.41

Week 6

0.2
units on a scale (Mean)
Standard Deviation: 1.45

Week 7

0.1
units on a scale (Mean)
Standard Deviation: 1.35

Week 8

Week 9

0.1
units on a scale (Mean)
Standard Deviation: 1.59

Placebo (Double-blind Maintenance Phase)

Week 1

0.3
units on a scale (Mean)
Standard Deviation: 1.17

Week 10

0.7
units on a scale (Mean)
Standard Deviation: 2.20

Week 11

0.8
units on a scale (Mean)
Standard Deviation: 2.23

Week 12

0.8
units on a scale (Mean)
Standard Deviation: 2.29

Week 2

0.4
units on a scale (Mean)
Standard Deviation: 1.46

Week 3

0.5
units on a scale (Mean)
Standard Deviation: 1.78

Week 4

0.8
units on a scale (Mean)
Standard Deviation: 1.86

Week 5

0.7
units on a scale (Mean)
Standard Deviation: 1.86

Week 6

0.7
units on a scale (Mean)
Standard Deviation: 1.95

Week 7

0.7
units on a scale (Mean)
Standard Deviation: 2.00

Week 8

0.8
units on a scale (Mean)
Standard Deviation: 2.06

Week 9

0.7
units on a scale (Mean)
Standard Deviation: 2.15

Rescue Medication Usage by Dose

Evaluation of the total amount of rescue medication used (number of doses per day, number of doses per week, and total number of doses while on-study)

Oxycodone DETERx (Double-blind Maintenance Phase)

Doses per Day

0.15
doses (Mean)
Standard Deviation: 0.297

Doses per Week

1.04
doses (Mean)
Standard Deviation: 2.081

Total Number of Doses

8.0
doses (Mean)
Standard Deviation: 16.38

Placebo (Double-blind Maintenance Phase)

Doses per Day

0.23
doses (Mean)
Standard Deviation: 0.458

Doses per Week

1.6
doses (Mean)
Standard Deviation: 3.206

Total Number of Doses

11.2
doses (Mean)
Standard Deviation: 31.55

Rescue Medication Use by Dosage

Evaluation of the total amount of rescue medication used (by milligrams of dosage per day, dosage per week, and total dosage while on-study)

Oxycodone DETERx (Double-blind Maintenance Phase)

Dosage per Day

144.63
milligrams (Mean)
Standard Deviation: 289.472

Dosage per Week

1012.39
milligrams (Mean)
Standard Deviation: 2026.298

Total Dosage

7873.1
milligrams (Mean)
Standard Deviation: 16665.70

Placebo (Double-blind Maintenance Phase)

Dosage per Day

189.32
milligrams (Mean)
Standard Deviation: 317.605

Dosage per Week

1325.27
milligrams (Mean)
Standard Deviation: 2223.231

Total Dosage

9028.1
milligrams (Mean)
Standard Deviation: 20441.67

Patient Global Impression of Change (PGIC)

The PGIC scale is a self-reported assessment that assesses a subject's impression of his/her change in activity limitations, symptoms, emotions, and the overall quality of life as they relate to his/her painful condition. The 7-point PGIC assessment includes "very much improved", "improved", "a little improved", "no change", "a little worse", "worse", and "very much worse".

Oxycodone DETERx (Double-blind Maintenance Phase)

A Little Improved

23.0
participants

A Little Worse

Improved

52.0
participants

No Change

9.0
participants

Very Much Improved

36.0
participants

Very Much Worse

Worse

2.0
participants

Placebo (Double-blind Maintenance Phase)

A Little Improved

26.0
participants

A Little Worse

4.0
participants

Improved

39.0
participants

No Change

12.0
participants

Very Much Improved

17.0
participants

Very Much Worse

1.0
participants

Worse

1.0
participants

Changes in Quality of Life

Short Form 12 Question Health Survey version 2 (SF-12v2) is a self-report survey designed to measure general quality of life from the subject's point of view. The survey includes eight domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. Physical (PCS) and mental component scores (MCS) are also calculated. Positive values indicate improvement from randomization baseline to Week 12.

Oxycodone DETERx (Double-blind Maintenance Phase)

Bodily Pain

0.7
units on a scale (Mean)
Standard Error: 1.16

General Health

0.28
units on a scale (Mean)
Standard Error: 0.784

Mental Component Score

-2.554
units on a scale (Mean)
Standard Error: 10.4145

Physical Component Score

7.524
units on a scale (Mean)
Standard Error: 10.1327

Physical Functioning

0.6
units on a scale (Mean)
Standard Error: 1.35

Role Physical

1.2
units on a scale (Mean)
Standard Error: 2.35

Placebo (Double-blind Maintenance Phase)

Bodily Pain

0.4
units on a scale (Mean)
Standard Error: 1.29

General Health

0.22
units on a scale (Mean)
Standard Error: 0.789

Mental Component Score

0.674
units on a scale (Mean)
Standard Error: 11.1676

Physical Component Score

3.622
units on a scale (Mean)
Standard Error: 9.4290

Physical Functioning

0.5
units on a scale (Mean)
Standard Error: 1.00

Role Physical

0.6
units on a scale (Mean)
Standard Error: 2.16

Change in Level of Physical Disability Using the Roland Morris Disability Questionnaire (RMDQ)

The Roland Morris Disability Questionnaire (RMDQ) is a self-administered questionnaire designed to assess physical disability caused by lower back pain. The RMDQ contains 24 sentences that subjects used to describe themselves when they have back pain. The RMDQ score is the total number of items checked which is from a minimum of 0 to a maximum of 24; the greater the score the grater the physical disability due to lower back pain.

Oxycodone DETERx (Double-blind Maintenance Phase)

0.4
units on a scale (Mean)
Standard Deviation: 4.83

Placebo (Double-blind Maintenance Phase)

0.7
units on a scale (Mean)
Standard Deviation: 5.32

Total

389
Participants

Age, Continuous

49.5
years (Mean)
Standard Deviation: 12.93

Pain Intensity-Numeric Rating Scale (PI-NRS)

2.9
units on a scale (Mean)
Standard Deviation: 1.00

Sex: Female, Male

Titration Phase

Oxycodone DETERx (Titration Phase)

Double-blind Maintenance Phase

Oxycodone DETERx (Double-blind Maintenance Phase)

Placebo (Double-blind Maintenance Phase)