Back Pain Lower Back Chronic
Conditions
Keywords
chronic pain, back pain
Brief summary
The purpose of the study is to evaluate the safety and efficacy of Hydrocodone Bitartrate controlled-release capsules in subjects with chronic low back pain.
Detailed description
A randomized Phase 3, placebo-controlled multi-center study to evaluate the safety, efficacy and tolerability of Hydrocodone Bitartrate controlled-release capsules in subjects with chronic low back pain. Subjects will go through an open-label conversion and titration phase followed by a randomized double-blind treatment phase of Hydrocodone (HC)-Controlled-Release (CR) vs. Placebo. The trial will consist of a Screening Phase (up to 14 days), an open-label Conversion and Titration Phase (up to 6 weeks), a 12-week placebo-controlled Treatment Phase, and a 2-week Follow-Up Phone Call
Interventions
DRUGPlacebo
Capsules, no active substance, shells identical to active comparator capsules
dosage form: capsule Strengths 10mg, 20mg, 30mg, 40mg, 50mg
Sponsors
Zogenix, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a clinical diagnosis of moderate to severe chronic lower back pain (CLBP) * Subjects must be classified as non-neuropathic, neuropathic, or symptomatic for more than 6 months after lower back pain (LBP) surgery * Subjects must in the Investigator's opinion qualify for around-the-clock opioid therapy for treatment of their chronic lower back pain (CLBP). * Subjects must have been taking opioids for at least 5 days/week for the past 4weeks * Subjects must have an average Clinic Pain Score of ≥ 4 on the 11-point (0-10) numeric rating scale (NRS) as an average for the last 24 hours of Screening * Subjects, in the opinion of the Investigator, must be considered to be in generally good health other then CLBP at Screening * Female subjects of childbearing potential must have a negative urine pregnancy test at the Screening Visit, and must consent to use a medically-acceptable method of contraception throughout the entire study period. * Subjects must voluntarily provide written informed consent.
Exclusion criteria
* Any clinically significant condition that would, in the opinion of the Investigator, preclude study participation or interfere with the assessment of pain and other symptoms of CLBP or increase the risk of opioid-related adverse events * A medical condition that, in the opinion of the Investigator, would compromise the subject's ability to swallow, absorb, metabolize, or excrete the study drug * A surgical procedure for back pain within 6 months * A nerve or plexus block, including epidural steroid injections or facet blocks * A history of chemotherapy or confirmed malignancy within past 2 years * Any other chronic pain condition other than CLBP that, in the Investigator's opinion, would interfere with the assessment of LBP e.g. fibromyalgia, osteoarthritis, rheumatoid arthritis, migraine headaches requiring opioid treatment * Uncontrolled blood pressure, i.e., subject has a sitting systolic blood pressure \>180 mmHg or \<90 mmHg, and/or a sitting diastolic blood pressure \>120 mmHg or \<50 mmHg at Screening * A Body Mass Index (BMI) \>45 kg/m2 * A Hospital Anxiety and Depression Scale (HADS) Index score of \>12 in either depression or anxiety subscales or an established history of major depressive disorder that is poorly controlled with medication * A clinically significant abnormality in clinical chemistry, hematology or urinalysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in 24-hour Pain Intensity Ratings Scale (NRS). | Baseline to Day 85 (Treatment Phase) | Change in average pain intensity as measured daily by Numeric Rating Scale (NRS) for Pain (0-10; where 0 = no pain, 10 = worst pain imaginable) comparing HC-ER with Placebo. Lower number equals better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change of the Clinic NRS Pain Intensity | Baseline to Day 85 visit | The change in pain intensity as measured in the clinic by a 0-10 Numeric Rating Scale (NRS) |
Countries
United States
Participant flow
Pre-assignment details
Out of 510 subjects treated with Hydrocodone Bitartrate Extended Release (HC-ER) capsules in the Conversion/Titration Phase, 208 subjects discontinued early and 151 subjects were randomized into each of the two treatment groups (Maintenance HC-ER Treatment and Placebo Treatment).
Participants by arm
| Arm | Count |
|---|---|
| Open-label Conversion/Titration Phase Hydrocodone Bitartrate Extended Release capsules twice daily for up to 6 weeks (Open-Label) | 510 |
| Total | 510 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Conversion/Titration | Adverse Event | 47 | 0 | 0 |
| Conversion/Titration | Lack of Efficacy | 17 | 0 | 0 |
| Conversion/Titration | Lost to Follow-up | 5 | 0 | 0 |
| Conversion/Titration | Non-Compliance | 47 | 0 | 0 |
| Conversion/Titration | Physician Decision | 2 | 0 | 0 |
| Conversion/Titration | Protocol Violation | 67 | 0 | 0 |
| Conversion/Titration | Withdrawal by Subject | 23 | 0 | 0 |
| Maintenance Treatment | Adverse Event | 0 | 2 | 12 |
| Maintenance Treatment | Lack of Efficacy | 0 | 14 | 64 |
| Maintenance Treatment | Lost to Follow-up | 0 | 1 | 0 |
| Maintenance Treatment | Non-Compliance | 0 | 4 | 7 |
| Maintenance Treatment | Physician Decision | 0 | 0 | 1 |
| Maintenance Treatment | Protocol Violation | 0 | 1 | 2 |
| Maintenance Treatment | Withdrawal by Medical Monitor | 0 | 0 | 1 |
| Maintenance Treatment | Withdrawal by Subject | 0 | 5 | 5 |
Baseline characteristics
| Characteristic | Open-label Conversion/Titration Phase |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 48 Participants |
| Age, Categorical Between 18 and 65 years | 462 Participants |
| Region of Enrollment United States | 510 participants |
| Sex: Female, Male Female | 273 Participants |
| Sex: Female, Male Male | 237 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 | 253 / 510 | 60 / 151 | 46 / 151 |
| serious Total, serious adverse events | 6 / 510 | 10 / 151 | 0 / 151 |
Outcome results
Primary
Mean Change in 24-hour Pain Intensity Ratings Scale (NRS).
Change in average pain intensity as measured daily by Numeric Rating Scale (NRS) for Pain (0-10; where 0 = no pain, 10 = worst pain imaginable) comparing HC-ER with Placebo. Lower number equals better outcome.
Time frame: Baseline to Day 85 (Treatment Phase)
Population: The primary efficacy analysis used the Intent to treat (ITT) population which included all 302 randomized subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydrocodone Bitartrate Capsules | Mean Change in 24-hour Pain Intensity Ratings Scale (NRS). | 0.48 units on a scale | Standard Deviation 1.563 |
| Placebo Comparator | Mean Change in 24-hour Pain Intensity Ratings Scale (NRS). | 0.96 units on a scale | Standard Deviation 1.55 |
Secondary
Mean Change of the Clinic NRS Pain Intensity
The change in pain intensity as measured in the clinic by a 0-10 Numeric Rating Scale (NRS)
Time frame: Baseline to Day 85 visit