Low Back Pain
Conditions
Keywords
Low back pain, Chronic pain, Opioid, Moderate to severe chronic low back pain
Brief summary
The primary objective of this study is to assess the efficacy and safety of OXN compared to placebo in opioid-experienced subjects with moderate to severe pain due to chronic low back pain who require around-the-clock opioid therapy.
Interventions
Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours
DRUGPlacebo
Placebo tablets to match OXN taken orally every 12 hours
Sponsors
Purdue Pharma LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
include: * Male and female subjects ≥ 18 years of age with moderate to severe, chronic low back pain (lasting at least several hours daily) as their predominant pain condition for at least 3 months prior to screening period; * The back pain must be related to nonmalignant and nonneuropathic conditions and without radiation or with only proximal radiation (above the knee); * Subjects must be on opioid analgesic therapy for low back pain which: * Has been ongoing for at least 4 weeks prior to the screening visit and, * Consists of a stable opioid regimen at a total average daily dose equivalent to 20 to 160 mg (inclusive) of morphine for the last 2 weeks prior to the screening visit. Subjects taking tramadol ≥ 100 mg daily on a stable regimen for the last 2 weeks prior to the screening visit will also meet this criterion; * Subjects must require continuation of opioid analgesic treatment in the range of 40 to 160 mg (inclusive) of morphine or its equivalent daily and be likely to benefit from chronic around-the-clock opioid therapy for the duration of the study; * Subjects must have an average pain over the last 14 days score ≥ 5 (on an 11-point numerical rating scale \[NRS\]) at the screening visit, on their current opioid analgesic medication and, if applicable, nonopioid medication; * Subjects must have an average pain over the last 24 hours score ≥ 5 (on an 11-point NRS) at the screening visit, on their current opioid analgesic medication and, if applicable, nonopioid medication; * Subjects must be willing and able to be compliant with the protocol, capable of subjective evaluation, able to read and understand questionnaires, willing and able to use a diary per protocol, and read, understand, and sign the written informed consent in English.
Exclusion criteria
include: * Female subjects who are pregnant (positive serum beta human chorionic gonadotropin \[β hCG\] test) or lactating; * Subjects with any contraindication or any history of hypersensitivity to oxycodone, naloxone, or other opioids. This does not include subjects who have experienced common opioid side effects (e.g., nausea, constipation); * Subjects with acute spinal cord compression, acute compression fracture, seronegative spondyloarthropathy, acute nerve root compression, cauda equina compression, fibromyalgia, reflex sympathetic dystrophy or causalgia (complex regional pain syndrome), diabetic amyotrophy, meningitis, discitis, or back pain due to secondary infection, tumor, or postherpetic neuralgia; * Subjects with gout, unless controlled on stable suppressive treatment with colchicine or uric-acid-lowering therapy without any attacks for ≥ 2 years and the subject has not been using nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors on a regular basis; * Subjects with pseudogout, psoriatic arthritis, active Lyme disease, rheumatoid arthritis or other inflammatory arthritis, or neuropathic pain conditions; * Subjects who had surgical procedures directed towards the source of chronic low back pain within 6 months of the screening visit or planned during the study; * Subjects with a history of opioid, alcohol, medication, or illicit drug abuse or addiction; * Subjects who have received any investigational medication within 30 days of first dose of study drug; * Subjects currently taking, or who have taken naloxone, naltrexone, methylnaltrexone, or alvimopan within 10 days before the screening visit; * Subjects who have received study drug in a clinical study of oxycodone/naloxone controlled-release (OXN or ONU). Other protocol specific inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Average Pain Over the Last 24 Hours at Week 12 of the Double-blind Period | 24 hours (Week 12) | The average pain over the last 24 hours score was collected using an 11-point numerical rating scale ranging from 0 to 10; where 0=no pain and 10=pain as bad as you can imagine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12 | Weeks 4, 8, and 12 | The scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of sleep, 3 somnolence, 1 snoring, 1 shortness of breath). Only Sleep Disturbance Subscale questions 1, 3, 7, and 8 were analyzed; scores range from 0 to 100, where higher scores indicate greater sleep disturbance. |
| Patient Global Impression of Change (PGIC) | Week 12 | The PGIC observational scale was completed by the subject. Subjects were asked to assess the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse), where 1 = very much improved and 7 = very much worse. The proportion of subjects responding much improved and very much improved was summarized by treatment group and compared between groups using an exact test. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline | Week 12 | A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the average pain over the last 24 hours score for week 12 of the double-blind period. |
| Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline | Week 12 | A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the average pain over the last 24 hours score for week 12 of the double-blind period. |
Countries
United States
Participant flow
Recruitment details
First subject first visit: 25-May-2011; Last subject last visit: 15-Oct-2012. The study was conducted at 132 medical/research sites in the United States.
Pre-assignment details
Opioid-experienced subjects with moderate to severe pain due to chronic low back pain, who required around-the-clock opioid therapy.
Participants by arm
| Arm | Count |
|---|---|
| OXN Group Oxycodone/Naloxone Controlled-release Tablets (OXN)
Oxycodone/Naloxone Controlled-release: Oxycodone/Naloxone Controlled-release tablets (10/5 mg, 20/10 mg, 30/15 mg, 40/20 mg) taken orally every 12 hours | 298 |
| Placebo Group Placebo tablets to match OXN
Placebo: Placebo tablets to match OXN taken orally every 12 hours | 302 |
| Total | 600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Phase | Administrative | 0 | 6 | 10 |
| Double-blind Phase | Adverse Event | 0 | 24 | 23 |
| Double-blind Phase | Confirmed or suspected diversion | 0 | 5 | 6 |
| Double-blind Phase | Lack of Efficacy | 0 | 31 | 73 |
| Double-blind Phase | Lost to Follow-up | 0 | 4 | 1 |
| Double-blind Phase | Withdrawal by Subject | 0 | 10 | 8 |
| Open-label Titration Period | Administrative | 8 | 0 | 0 |
| Open-label Titration Period | Adverse Event | 95 | 0 | 0 |
| Open-label Titration Period | Confirmed or suspected diversion | 16 | 0 | 0 |
| Open-label Titration Period | Did not qualify | 178 | 0 | 0 |
| Open-label Titration Period | Lack of Efficacy | 107 | 0 | 0 |
| Open-label Titration Period | Lost to Follow-up | 25 | 0 | 0 |
| Open-label Titration Period | Withdrawal by Subject | 65 | 0 | 0 |
Baseline characteristics
| Characteristic | OXN Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 11.69 | 53.0 years STANDARD_DEVIATION 10.97 | 53.2 years STANDARD_DEVIATION 11.33 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants | 3 participants | 4 participants |
| Race/Ethnicity, Customized Asian | 8 participants | 3 participants | 11 participants |
| Race/Ethnicity, Customized Black or African American | 53 participants | 61 participants | 114 participants |
| Race/Ethnicity, Customized Other | 7 participants | 2 participants | 9 participants |
| Race/Ethnicity, Customized White | 229 participants | 233 participants | 462 participants |
| Sex: Female, Male Female | 162 Participants | 176 Participants | 338 Participants |
| Sex: Female, Male Male | 136 Participants | 126 Participants | 262 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 79 / 1,095 | 34 / 302 | 41 / 298 |
| serious Total, serious adverse events | 11 / 1,095 | 12 / 302 | 19 / 298 |
Outcome results
Primary
The Average Pain Over the Last 24 Hours at Week 12 of the Double-blind Period
The average pain over the last 24 hours score was collected using an 11-point numerical rating scale ranging from 0 to 10; where 0=no pain and 10=pain as bad as you can imagine.
Time frame: 24 hours (Week 12)
Population: The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OXN Group | The Average Pain Over the Last 24 Hours at Week 12 of the Double-blind Period | 3.86 units on a scale (0 - 10) | Standard Error 0.116 |
| Placebo Group | The Average Pain Over the Last 24 Hours at Week 12 of the Double-blind Period | 4.32 units on a scale (0 - 10) | Standard Error 0.115 |
p-value: 0.005595% CI: [0.13, 0.77]Mixed Models Analysis
Secondary
Patient Global Impression of Change (PGIC)
The PGIC observational scale was completed by the subject. Subjects were asked to assess the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse), where 1 = very much improved and 7 = very much worse. The proportion of subjects responding much improved and very much improved was summarized by treatment group and compared between groups using an exact test.
Time frame: Week 12
Population: The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OXN Group | Patient Global Impression of Change (PGIC) | 153 participants (responders) |
| Placebo Group | Patient Global Impression of Change (PGIC) | 109 participants (responders) |
p-value: 0.0002Fisher Exact
Secondary
The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12
The scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of sleep, 3 somnolence, 1 snoring, 1 shortness of breath). Only Sleep Disturbance Subscale questions 1, 3, 7, and 8 were analyzed; scores range from 0 to 100, where higher scores indicate greater sleep disturbance.
Time frame: Weeks 4, 8, and 12
Population: The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| OXN Group | The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12 | Week 8 | 30.8 units on a scale |
| OXN Group | The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12 | Week 4 | 32.5 units on a scale |
| OXN Group | The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12 | Week 12 | 31.1 units on a scale |
| Placebo Group | The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12 | Week 4 | 38.0 units on a scale |
| Placebo Group | The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12 | Week 8 | 36.8 units on a scale |
| Placebo Group | The Sleep Disturbance Subscale of the MOS Sleep Scale at Weeks 4, 8, and 12 | Week 12 | 36.4 units on a scale |
p-value: 0.019195% CI: [0.9, 9.8]Mixed Models Analysis
Other Pre-specified
Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline
A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the average pain over the last 24 hours score for week 12 of the double-blind period.
Time frame: Week 12
Population: The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OXN Group | Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline | 164 participants (responders) |
| Placebo Group | Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline | 124 participants (responders) |
Comparison: Proportion of subjects with a response to treatment that is ≥ 30%p-value: 0.0006Cochran-Mantel-Haenszel
Other Pre-specified
Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline
A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the average pain over the last 24 hours score for week 12 of the double-blind period.
Time frame: Week 12
Population: The full analysis population for efficacy (N = 600) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OXN Group | Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline | 109 participants (responders) |
| Placebo Group | Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline | 75 participants (responders) |
Comparison: Proportion of subjects with a response to treatment that is ≥ 50%p-value: 0.0018Cochran-Mantel-Haenszel