Chronic Low Back Pain
Conditions
Brief summary
The primary purpose of this study was to evaluate the analgesic effect and safety of hydrocodone/acetaminophen extended release compared to placebo.
Detailed description
This phase 2, multicenter, double-blind (DB), placebo-controlled, randomized withdrawal study compared the analgesic efficacy and safety of hydrocodone/acetaminophen extended release to placebo in subjects with moderate to moderately severe chronic lower back pain (CLBP). Participants met pre-defined criteria at the conclusion of the open-label (OL) Titration Period to proceed to randomization into the double-blind (DB) Maintenance Period of the study. Study drug was given for a total of approximately 5 weeks, which included 2 weeks in OL, 2 weeks in DB, and a 3-day taper. During the OL period, all participants took increasing doses of hydrocodone/acetaminophen extended release until they were taking 2 tablets, twice daily. During the DB period, participants in the hydrocodone/acetaminophen extended release group took 1 hydrocodone/acetaminophen extended release tablet twice daily throughout the 2 weeks, while participants in the placebo group took 1 placebo tablet twice daily.
Interventions
DRUGPlacebo
Sponsors
AbbVie (prior sponsor, Abbott)
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
Adult subjects who have a diagnosis of chronic low back pain of at least 6 month duration
Exclusion criteria
Subjects with a history of surgical or invasive intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Double-blind Baseline in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS) | Double-blind baseline to Day 29 | The change from the double-blind randomization baseline (DB baseline: the last assessment before first dose in the double-blind period) to the final assessment in pain intensity, assessed using the CLBP Intensity VAS (0 mm = No Pain and 100 mm = Worst Pain Imaginable). Least squares means and standard errors from an ANCOVA model. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participant's Global Assessment of Back Pain Status at Final Evaluation | Double-blind baseline to Day 29 | The participant's overall impression of their back pain status was obtained by having the participant answer the question Considering all the ways your chronic low back pain affects you, how are you doing today? on a 5-point categorical scale: very good (no symptoms and no limitation of normal activities); good (mild symptoms and no limitation of normal activities); fair (moderate symptoms and limitation of some normal activities); poor (severe symptoms and inability to carry out most normal activities); very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). |
| Participant's Global Assessment of Study Drug at Final Evaluation | Double-blind baseline to Day 29 | The participant's overall impression of the study drug was obtained by having the participant answer the question How would you rate your overall response to the study medication? on a 5-point categorical scale: excellent; very good; good; fair; poor. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OL Hydrocodone/Acetaminophen Extended Release (Nonrandomized) 2 hydrocodone/acetaminophen extended release tablets, twice daily, for 2 weeks. These participants enrolled in the study and received at least one dose of study drug during the open-label period; these participants were not randomized and did not progress to the double-blind period. | 22 |
| DB Hydrocodone/Acetaminophen Extended Release 1 hydrocodone/acetaminophen extended release tablet, twice daily, for 2 weeks. These participants completed the open-label period (hydrocodone/acetaminophen extended release, 2 tablets twice daily), and were randomized to receive hydrocodone/acetaminophen extended release during the double-blind period. | 99 |
| DB Placebo 1 placebo tablet, twice daily, for 2 weeks. These participants completed the open-label period (hydrocodone/acetaminophen extended release, 2 tablets twice daily), and were randomized to receive placebo during the double-blind period. | 47 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind (DB) Period | Adverse Event | 0 | 0 | 1 |
| Double-Blind (DB) Period | Lack of Efficacy | 0 | 3 | 4 |
| Double-Blind (DB) Period | Other, Unspecified | 0 | 1 | 0 |
| Double-Blind (DB) Period | Subject Noncompliant | 0 | 1 | 0 |
| Open-label (OL) Period | Adverse Event | 7 | 0 | 0 |
| Open-label (OL) Period | Did Not Meet Randomization Criteria | 6 | 0 | 0 |
| Open-label (OL) Period | Lack of Efficacy | 3 | 0 | 0 |
| Open-label (OL) Period | Lost to Follow-up | 1 | 0 | 0 |
| Open-label (OL) Period | Other, Unspecified | 1 | 0 | 0 |
| Open-label (OL) Period | Withdrawal by Subject | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | OL Hydrocodone/Acetaminophen Extended Release (Nonrandomized) | DB Hydrocodone/Acetaminophen Extended Release | DB Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 51.0 years STANDARD_DEVIATION 13.82 | 47.9 years STANDARD_DEVIATION 13.62 | 52.7 years STANDARD_DEVIATION 13.82 | 49.7 years STANDARD_DEVIATION 13.79 |
| Double-blind Baseline Chronic Lower Back Pain (CLBP) Intensity VAS | NA scores on a scale | 26.9 scores on a scale STANDARD_DEVIATION 13.78 | 31.7 scores on a scale STANDARD_DEVIATION 11.17 | 28.5 scores on a scale STANDARD_DEVIATION 13.14 |
| Double-blind Participant's Global Assessment of Back Pain Status Fair | NA participants | 21 participants | 14 participants | NA participants |
| Double-blind Participant's Global Assessment of Back Pain Status Good | NA participants | 57 participants | 29 participants | NA participants |
| Double-blind Participant's Global Assessment of Back Pain Status Poor | NA participants | 2 participants | 0 participants | NA participants |
| Double-blind Participant's Global Assessment of Back Pain Status Very Good | NA participants | 15 participants | 3 participants | NA participants |
| Sex: Female, Male Female | 15 Participants | 61 Participants | 30 Participants | 106 Participants |
| Sex: Female, Male Male | 7 Participants | 38 Participants | 17 Participants | 62 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 | 70 / 168 | 7 / 99 | 8 / 47 |
| serious Total, serious adverse events | 0 / 168 | 0 / 99 | 1 / 47 |
Outcome results
Primary
Change From Double-blind Baseline in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS)
The change from the double-blind randomization baseline (DB baseline: the last assessment before first dose in the double-blind period) to the final assessment in pain intensity, assessed using the CLBP Intensity VAS (0 mm = No Pain and 100 mm = Worst Pain Imaginable). Least squares means and standard errors from an ANCOVA model.
Time frame: Double-blind baseline to Day 29
Population: The analysis of the primary outcome measure included all randomized participants who received at least 1 dose of study drug during the double-blind period (double-blind intent-to-treat) and had at least 1 assessment during the double-blind period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Hydrocodone/Acetaminophen Extended Release | Change From Double-blind Baseline in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS) | 10.9 scores on a scale | Standard Error 2.86 |
| Double-blind Placebo | Change From Double-blind Baseline in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS) | 19.9 scores on a scale | Standard Error 3.77 |
Secondary
Participant's Global Assessment of Back Pain Status at Final Evaluation
The participant's overall impression of their back pain status was obtained by having the participant answer the question Considering all the ways your chronic low back pain affects you, how are you doing today? on a 5-point categorical scale: very good (no symptoms and no limitation of normal activities); good (mild symptoms and no limitation of normal activities); fair (moderate symptoms and limitation of some normal activities); poor (severe symptoms and inability to carry out most normal activities); very poor (very severe symptoms which are intolerable and inability to carry out all normal activities).
Time frame: Double-blind baseline to Day 29
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Back Pain Status at Final Evaluation | Good | 47 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Back Pain Status at Final Evaluation | Poor | 10 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Back Pain Status at Final Evaluation | Fair | 25 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Back Pain Status at Final Evaluation | Very Poor | 0 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Back Pain Status at Final Evaluation | Very Good | 13 participants |
| Double-blind Placebo | Participant's Global Assessment of Back Pain Status at Final Evaluation | Very Poor | 0 participants |
| Double-blind Placebo | Participant's Global Assessment of Back Pain Status at Final Evaluation | Very Good | 2 participants |
| Double-blind Placebo | Participant's Global Assessment of Back Pain Status at Final Evaluation | Good | 16 participants |
| Double-blind Placebo | Participant's Global Assessment of Back Pain Status at Final Evaluation | Fair | 19 participants |
| Double-blind Placebo | Participant's Global Assessment of Back Pain Status at Final Evaluation | Poor | 9 participants |
Secondary
Participant's Global Assessment of Study Drug at Final Evaluation
The participant's overall impression of the study drug was obtained by having the participant answer the question How would you rate your overall response to the study medication? on a 5-point categorical scale: excellent; very good; good; fair; poor.
Time frame: Double-blind baseline to Day 29
Population: Double-blind intent to treat population; scores for participants with no post-randomization assessment were excluded from this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Study Drug at Final Evaluation | Very Good | 11 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Study Drug at Final Evaluation | Fair | 31 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Study Drug at Final Evaluation | Good | 36 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Study Drug at Final Evaluation | Poor | 13 participants |
| Double-blind Hydrocodone/Acetaminophen Extended Release | Participant's Global Assessment of Study Drug at Final Evaluation | Excellent | 2 participants |
| Double-blind Placebo | Participant's Global Assessment of Study Drug at Final Evaluation | Poor | 5 participants |
| Double-blind Placebo | Participant's Global Assessment of Study Drug at Final Evaluation | Excellent | 7 participants |
| Double-blind Placebo | Participant's Global Assessment of Study Drug at Final Evaluation | Very Good | 4 participants |
| Double-blind Placebo | Participant's Global Assessment of Study Drug at Final Evaluation | Good | 19 participants |
| Double-blind Placebo | Participant's Global Assessment of Study Drug at Final Evaluation | Fair | 11 participants |