Chronic Low Back Pain
Conditions
Keywords
Effect on sleep interference by pain
Brief summary
The primary purpose of the study is to test the efficacy of 2 tablets (twice daily) of ABT-712, compared to placebo, administered over a 4-week period in participants with moderate to severe mechanical chronic low back pain (CLBP).
Detailed description
The study used a randomized withdrawal design with an open label (OL) period prior to a double-blind (DB) period. Participants who were receiving benefit and were tolerating ABT-712 during the OL period were randomized into the DB period. Study drug was given for a total of 8 weeks, which included up to 3 weeks in OL, up to 4 weeks in DB, and a 1-week DB taper. During the OL period, all participants took increasing doses of ABT-712 until they were taking 2 tablets, twice daily. During the DB period, participants in the ABT-712 group took 2 ABT-712 tablets, twice daily throughout the 4 weeks, while participants in the placebo group took 2 placebo tablets twice daily.
Interventions
DRUGABT-712
ABT-712 extended-release tablet
DRUGPlacebo
Placebo tablet
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult male and female subjects who voluntarily sign the informed consent * Diagnosis of CLBP of 6 months duration
Exclusion criteria
* Incapacitated or bedridden subjects * Subjects with history of surgical or invasive intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Double-blind (DB) Baseline to Final Assessment in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS) | Double-blind baseline to 4 weeks | The change from the DB randomization baseline (DB baseline: the last assessment before first dose in the DB 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 2-way ANCOVA model without interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Double-blind baseline to 4 weeks | The change from the DB randomization baseline (DB baseline: the last assessment before first dose in the DB period) to the final assessment of the impact of pain on the participant's sleep. The CPSI utilizes a 100 mm VAS scale for questions of how often the participant had trouble falling asleep because of pain, needed sleeping medication, was awakened by pain during the night, and was awakened by pain in the morning (0 mm = Never and 100 mm = Always); and for rating the overall quality of sleep (0 mm = Very Poor and 100 mm = Excellent). Least squares means and standard errors from 2-way ANCOVA model without interaction. |
Countries
United States
Participant flow
Pre-assignment details
Out of the 287 participants enrolled in the study, 285 participants were treated; 2 participants did not receive treatment during the open-label treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Nonrandomized 2 ABT-712 extended-release tablets, twice daily, for up to 3 weeks during the open-label period. These participants enrolled in the study and received at least 1 dose of study drug, and either discontinued during the open-label period or were not randomized and did not progress to the double-blind period. | 63 |
| Double-blind ABT-712 2 ABT-712 extended-release tablets, twice daily, for 4 weeks (double-blind period). | 109 |
| Double-blind Placebo 2 placebo tablets, twice daily, for 4 weeks (double-blind period). | 113 |
| Total | 285 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Period | Adverse Event | 0 | 4 | 4 |
| Double-blind Period | Lack of Efficacy | 0 | 9 | 17 |
| Double-blind Period | Lost to Follow-up | 0 | 4 | 2 |
| Double-blind Period | Other | 0 | 2 | 3 |
| Double-blind Period | Withdrawal by Subject | 0 | 2 | 3 |
| Open-label Period | Adverse Event | 24 | 0 | 0 |
| Open-label Period | Did not meet DB randomization criteria | 5 | 0 | 0 |
| Open-label Period | Lack of Efficacy | 2 | 0 | 0 |
| Open-label Period | Lost to Follow-up | 14 | 0 | 0 |
| Open-label Period | Other | 4 | 0 | 0 |
| Open-label Period | Subject noncompliant | 7 | 0 | 0 |
| Open-label Period | Withdrawal by Subject | 7 | 0 | 0 |
Baseline characteristics
| Characteristic | Nonrandomized | Double-blind ABT-712 | Double-blind Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 46.1 years STANDARD_DEVIATION 12.25 | 49.6 years STANDARD_DEVIATION 12.44 | 48.1 years STANDARD_DEVIATION 11.21 | 48.2 years STANDARD_DEVIATION 11.95 |
| Double-blind Baseline CLBP Intensity VAS | NA scores on a scale | 24.2 scores on a scale STANDARD_DEVIATION 15.61 | 23.2 scores on a scale STANDARD_DEVIATION 15.01 | 23.7 scores on a scale STANDARD_DEVIATION 15.28 |
| Double-blind Baseline Sleep Interference by Pain Scale | NA scores on a scale | 2.2 scores on a scale STANDARD_DEVIATION 2.02 | 2.3 scores on a scale STANDARD_DEVIATION 2.16 | 2.2 scores on a scale STANDARD_DEVIATION 2.09 |
| Sex: Female, Male Female | 34 Participants | 64 Participants | 59 Participants | 157 Participants |
| Sex: Female, Male Male | 29 Participants | 45 Participants | 54 Participants | 128 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 | 146 / 285 | 31 / 109 | 16 / 113 |
| serious Total, serious adverse events | 1 / 285 | 1 / 109 | 1 / 113 |
Outcome results
Primary
Change From Double-blind (DB) Baseline to Final Assessment in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS)
The change from the DB randomization baseline (DB baseline: the last assessment before first dose in the DB 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 2-way ANCOVA model without interaction.
Time frame: Double-blind baseline to 4 weeks
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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Double-blind ABT-712 | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS) | 1.2 scores on a scale | Standard Error 2.57 |
| Double-blind Placebo | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Lower Back Pain (CLBP) Intensity by Visual Analog Scale (VAS) | 23.0 scores on a scale | Standard Error 2.54 |
Secondary
Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI)
The change from the DB randomization baseline (DB baseline: the last assessment before first dose in the DB period) to the final assessment of the impact of pain on the participant's sleep. The CPSI utilizes a 100 mm VAS scale for questions of how often the participant had trouble falling asleep because of pain, needed sleeping medication, was awakened by pain during the night, and was awakened by pain in the morning (0 mm = Never and 100 mm = Always); and for rating the overall quality of sleep (0 mm = Very Poor and 100 mm = Excellent). Least squares means and standard errors from 2-way ANCOVA model without interaction.
Time frame: Double-blind baseline to 4 weeks
Population: The analysis of the secondary outcome measure included all randomized participants who received at least 1 dose of study drug during the DB period (DB intent-to-treat), had a DB baseline assessment, and had at least 1 assessment during the DB period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind ABT-712 | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Needed Sleeping Medication | -1.2 scores on a scale | Standard Error 2.3 |
| Double-blind ABT-712 | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Awakened by Pain in the Morning | -4.5 scores on a scale | Standard Error 2.72 |
| Double-blind ABT-712 | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Awakened by Pain During the Night | -5.0 scores on a scale | Standard Error 2.61 |
| Double-blind ABT-712 | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Quality of Sleep | -0.4 scores on a scale | Standard Error 3.04 |
| Double-blind ABT-712 | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Trouble Falling Asleep | -3.7 scores on a scale | Standard Error 2.75 |
| Double-blind Placebo | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Quality of Sleep | -23.2 scores on a scale | Standard Error 3.06 |
| Double-blind Placebo | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Trouble Falling Asleep | 18.7 scores on a scale | Standard Error 2.77 |
| Double-blind Placebo | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Needed Sleeping Medication | 13.5 scores on a scale | Standard Error 2.32 |
| Double-blind Placebo | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Awakened by Pain During the Night | 19.5 scores on a scale | Standard Error 2.63 |
| Double-blind Placebo | Change From Double-blind (DB) Baseline to Final Assessment in Chronic Pain Sleep Inventory (CPSI) | Awakened by Pain in the Morning | 20.1 scores on a scale | Standard Error 2.74 |