Chronic Low Back Pain
Conditions
Keywords
Low back pain, Chronic back pain, Back pain, Opioid, Oxycodone, DETERx, Chronic pain, Chronic low back pain, CLBP, Xtampza
Brief summary
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.
Interventions
DRUGOxycodone DETERx
40-160 mg total daily dose of oxycodone DETERx, divided into 2 doses, q12h
DRUGPlacebo
Placebo, divided into 2 doses, q12h
Sponsors
Collegium Pharmaceutical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Randomized Baseline through Week 12 | The PI-NRS is an 11-point numerical rating scale ranging from 0 (no pain) to 10 (worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in Pain Intensity for Responders | Screening Baseline through Week 12 | 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. |
| Weekly Changes in Pain Intensity | Randomization Baseline and weekly through Week 12 | 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). |
| Rescue Medication Usage by Dose | Randomization Baseline through Week 12 | 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) |
| Time-to-exit From the Study for All Causes | Randomization Baseline through Week 12 | 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. |
| Patient Global Impression of Change (PGIC) | Screening Baseline through Week 12 | 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. |
| Changes in Quality of Life | Randomization Baseline through Week 12 | 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. |
| Change in Level of Physical Disability Using the Roland Morris Disability Questionnaire (RMDQ) | Randomization Baseline and Week 12 | 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. |
| Rescue Medication Use by Dosage | Randomization Baseline through Week 12 | Evaluation of the total amount of rescue medication used (by milligrams of dosage per day, dosage per week, and total dosage while on-study) |
Countries
United States
Participant flow
Pre-assignment details
The titration (i.e., enrichment) phase of the study was designed to titrate patients to a dose of Oxycodone DETERx that balanced pain control and tolerability to ensure that only patients who experienced a substantial reduction from the screening pain assessment and who can tolerate side effects continue into the Double-blind Maintenance Phase.
Participants by arm
| Arm | Count |
|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | 193 |
| Placebo (Double-blind Maintenance Phase) | 196 |
| Total | 389 |
Baseline characteristics
| Characteristic | Oxycodone DETERx (Double-blind Maintenance Phase) | Placebo (Double-blind Maintenance Phase) | Total |
|---|---|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 13.31 | 49.9 years STANDARD_DEVIATION 12.56 | 49.5 years STANDARD_DEVIATION 12.93 |
| Pain Intensity-Numeric Rating Scale (PI-NRS) | 3.0 units on a scale STANDARD_DEVIATION 1.04 | 2.9 units on a scale STANDARD_DEVIATION 0.97 | 2.9 units on a scale STANDARD_DEVIATION 1 |
| Sex: Female, Male Female | 103 Participants | 103 Participants | 206 Participants |
| Sex: Female, Male Male | 90 Participants | 93 Participants | 183 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 531 / 740 | 60 / 193 | 39 / 196 |
| serious Total, serious adverse events | 2 / 1,297 | 8 / 740 | 2 / 193 | 2 / 196 |
Outcome results
Primary
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).
Time frame: Randomized Baseline through Week 12
Population: One subject is missing all Average Weekly Pain Scores after Screening in the Oxycodone DETERx treatment group. This subject has been excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxycodone DETERx (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 | 0.29 units on a scale | Standard Error 0.146 |
| 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 | 1.85 units on a scale | Standard Error 0.223 |
p-value: <0.0001z-test
Secondary
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.
Time frame: Randomization Baseline and Week 12
Population: The RMDQ was analyzed and presented as a change from Randomization Baseline to Week 12. Subjects' scores from Early Discontinuation visits were not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Change in Level of Physical Disability Using the Roland Morris Disability Questionnaire (RMDQ) | 0.4 units on a scale | Standard Deviation 4.83 |
| Placebo (Double-blind Maintenance Phase) | Change in Level of Physical Disability Using the Roland Morris Disability Questionnaire (RMDQ) | 0.7 units on a scale | Standard Deviation 5.32 |
Secondary
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.
Time frame: Randomization Baseline through Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Changes in Quality of Life | Physical Functioning | 0.6 units on a scale | Standard Error 1.35 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Changes in Quality of Life | General Health | 0.28 units on a scale | Standard Error 0.784 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Changes in Quality of Life | Role Physical | 1.2 units on a scale | Standard Error 2.35 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Changes in Quality of Life | Mental Component Score | -2.554 units on a scale | Standard Error 10.4145 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Changes in Quality of Life | Bodily Pain | 0.7 units on a scale | Standard Error 1.16 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Changes in Quality of Life | Physical Component Score | 7.524 units on a scale | Standard Error 10.1327 |
| Placebo (Double-blind Maintenance Phase) | Changes in Quality of Life | Bodily Pain | 0.4 units on a scale | Standard Error 1.29 |
| Placebo (Double-blind Maintenance Phase) | Changes in Quality of Life | General Health | 0.22 units on a scale | Standard Error 0.789 |
| Placebo (Double-blind Maintenance Phase) | Changes in Quality of Life | Physical Component Score | 3.622 units on a scale | Standard Error 9.429 |
| Placebo (Double-blind Maintenance Phase) | Changes in Quality of Life | Mental Component Score | 0.674 units on a scale | Standard Error 11.1676 |
| Placebo (Double-blind Maintenance Phase) | Changes in Quality of Life | Physical Functioning | 0.5 units on a scale | Standard Error 1 |
| Placebo (Double-blind Maintenance Phase) | Changes in Quality of Life | Role Physical | 0.6 units on a scale | Standard Error 2.16 |
Secondary
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.
Time frame: Screening Baseline through Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Worse | 2 participants |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Very Much Worse | 0 participants |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Improved | 52 participants |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | A Little Improved | 23 participants |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | No Change | 9 participants |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | A Little Worse | 0 participants |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Very Much Improved | 36 participants |
| Placebo (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | No Change | 12 participants |
| Placebo (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Very Much Improved | 17 participants |
| Placebo (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Worse | 1 participants |
| Placebo (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | A Little Improved | 26 participants |
| Placebo (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Very Much Worse | 1 participants |
| Placebo (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | A Little Worse | 4 participants |
| Placebo (Double-blind Maintenance Phase) | Patient Global Impression of Change (PGIC) | Improved | 39 participants |
Secondary
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.
Time frame: Screening Baseline through Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Percent Reduction in Pain Intensity for Responders | Subjects with 50% Improvement | 74 participants |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Percent Reduction in Pain Intensity for Responders | Subjects with 30% Improvement | 95 participants |
| Placebo (Double-blind Maintenance Phase) | Percent Reduction in Pain Intensity for Responders | Subjects with 50% Improvement | 48 participants |
| Placebo (Double-blind Maintenance Phase) | Percent Reduction in Pain Intensity for Responders | Subjects with 30% Improvement | 65 participants |
Secondary
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)
Time frame: Randomization Baseline through Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Rescue Medication Usage by Dose | Doses per Day | 0.15 doses | Standard Deviation 0.297 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Rescue Medication Usage by Dose | Doses per Week | 1.04 doses | Standard Deviation 2.081 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Rescue Medication Usage by Dose | Total Number of Doses | 8.0 doses | Standard Deviation 16.38 |
| Placebo (Double-blind Maintenance Phase) | Rescue Medication Usage by Dose | Doses per Day | 0.23 doses | Standard Deviation 0.458 |
| Placebo (Double-blind Maintenance Phase) | Rescue Medication Usage by Dose | Doses per Week | 1.60 doses | Standard Deviation 3.206 |
| Placebo (Double-blind Maintenance Phase) | Rescue Medication Usage by Dose | Total Number of Doses | 11.2 doses | Standard Deviation 31.55 |
Secondary
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)
Time frame: Randomization Baseline through Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Rescue Medication Use by Dosage | Dosage per Day | 144.63 milligrams | Standard Deviation 289.472 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Rescue Medication Use by Dosage | Dosage per Week | 1012.39 milligrams | Standard Deviation 2026.298 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Rescue Medication Use by Dosage | Total Dosage | 7873.1 milligrams | Standard Deviation 16665.7 |
| Placebo (Double-blind Maintenance Phase) | Rescue Medication Use by Dosage | Dosage per Day | 189.32 milligrams | Standard Deviation 317.605 |
| Placebo (Double-blind Maintenance Phase) | Rescue Medication Use by Dosage | Dosage per Week | 1325.27 milligrams | Standard Deviation 2223.231 |
| Placebo (Double-blind Maintenance Phase) | Rescue Medication Use by Dosage | Total Dosage | 9028.1 milligrams | Standard Deviation 20441.67 |
Secondary
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.
Time frame: Randomization Baseline through Week 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Time-to-exit From the Study for All Causes | 58.0 Days |
| Placebo (Double-blind Maintenance Phase) | Time-to-exit From the Study for All Causes | 35.0 Days |
Secondary
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).
Time frame: Randomization Baseline and weekly through Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 1 | 0.1 units on a scale | Standard Deviation 0.85 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 2 | 0.0 units on a scale | Standard Deviation 1.05 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 3 | 0.1 units on a scale | Standard Deviation 1.14 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 4 | 0.1 units on a scale | Standard Deviation 1.25 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 5 | 0.2 units on a scale | Standard Deviation 1.41 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 6 | 0.2 units on a scale | Standard Deviation 1.45 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 7 | 0.1 units on a scale | Standard Deviation 1.35 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 8 | 0.0 units on a scale | Standard Deviation 1.29 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 9 | 0.1 units on a scale | Standard Deviation 1.59 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 10 | 0.2 units on a scale | Standard Deviation 1.55 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 11 | 0.2 units on a scale | Standard Deviation 1.62 |
| Oxycodone DETERx (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 12 | 0.3 units on a scale | Standard Deviation 1.54 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 11 | 0.8 units on a scale | Standard Deviation 2.23 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 1 | 0.3 units on a scale | Standard Deviation 1.17 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 7 | 0.7 units on a scale | Standard Deviation 2 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 2 | 0.4 units on a scale | Standard Deviation 1.46 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 10 | 0.7 units on a scale | Standard Deviation 2.2 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 3 | 0.5 units on a scale | Standard Deviation 1.78 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 8 | 0.8 units on a scale | Standard Deviation 2.06 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 4 | 0.8 units on a scale | Standard Deviation 1.86 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 12 | 0.8 units on a scale | Standard Deviation 2.29 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 5 | 0.7 units on a scale | Standard Deviation 1.86 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 9 | 0.7 units on a scale | Standard Deviation 2.15 |
| Placebo (Double-blind Maintenance Phase) | Weekly Changes in Pain Intensity | Week 6 | 0.7 units on a scale | Standard Deviation 1.95 |