Pain
Conditions
Brief summary
The purpose of this study was to evaluate analgesic efficacy and safety of hydrocodone/acetaminophen compared to placebo in moderate to severe pain following molar extraction.
Detailed description
Dosing started within 6 hours after completion of third molar extraction. Study drug was given once every 6 hours for 12 hours (for a total of 2 doses). Participants were randomized to receive placebo or active drug (either experimental drug or comparator). The total dose was the same for both groups receiving active drug, but was given as either 1 dose of extended-release tablets (experimental drug), or 2 doses of immediate-release tablets (active comparator).
Interventions
DRUGABT-712 Extended-release
ABT-712 extended-release tablet
DRUGHydrocodone/Acetaminophen Immediate-release
Hydrocodone/acetaminophen immediate-release tablet
DRUGPlacebo
Placebo tablet
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who are in general good health, experiencing moderate to severe pain after surgical extraction of 2 or more third molars and who are willing to remain confined until the morning after surgery for study procedures
Exclusion criteria
* Allergies to study medications * History of multiple drug allergies * Unable to stop excluded medications * Clinically significant laboratory abnormalities at Screening * Significant medical condition at Screening * Women who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference (SPID) Using the Pain Intensity Visual Analog Scale (VAS) | From time of first study drug administration to 12 hours following first study drug administration | Participants assessed pain intensity on a 100 mm visual analogue scale (VAS) with 0 meaning no pain and 100 meaning the worst pain imaginable. The SPID VAS score for 0 to 12 hours following initial study drug dose measured the cumulative pain intensity difference during treatment with higher mean SPID VAS scores indicating greater improvement from Baseline. The SPID score is a measure of the cumulative pain intensity difference during treatment and the area under the curve was estimated using the linear trapezoidal rule. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TOTPAR (Total Pain Relief) | From time of first study drug administration to 12 hours following first study drug administration | TOTPAR was the time-interval weighted sum of pain relief. Pain relief was assessed by participants' responses to how their pain relief was compared with the pain they had just before receiving the first dose of study drug: no relief, a little relief, some relief, a lot of relief, or complete relief. Higher mean TOTPAR scores indicate better pain relief. The TOTPAR score is a measure of the cumulative pain intensity difference during treatment and the area under the curve was estimated using the linear trapezoidal rule. |
| Time to First Rescue Medication | From time of first study drug administration to 12 hours following first study drug administration | The median time (minutes) from first dose of study drug to first use of analgesic rescue medication. |
| Participants With Adverse Events (AEs) | AEs were recorded from study drug administration until 30 days following discontinuation of study drug (total 30 days); SAEs were recorded from the time informed consent was obtained until 30 days following discontinuation of study drug (total 51 days). | An adverse event (AE) is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with treatment. If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): results in death or is life-threatening, results in admission or prolongation of hospitalization, results in congenital anomaly or persistent or significant disability/incapacity, or is an important medical event requiring medical or surgical intervention to prevent serious outcome. AEs were categorized by severity (mild, moderate, severe) and relationship to treatment (probably, possibly, probably not, not related). Please see Adverse Events section below for more details. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABT-712 1 dose of 1 ABT-712 extended-release tablet plus 1 placebo tablet, followed by 1 dose of 2 placebo tablets, administered once every 6 hours for 12 hours (for a total of 2 doses). | 43 |
| Hydrocodone/Acetaminophen 2 doses of 1 hydrocodone/acetaminophen immediate-release tablet plus 1 placebo tablet, administered once every 6 hours for 12 hours (for a total of 2 doses). | 39 |
| Placebo 2 doses of 2 placebo tablets, administered once every 6 hours for 12 hours (for a total of 2 doses). | 40 |
| Total | 122 |
Baseline characteristics
| Characteristic | ABT-712 | Hydrocodone/Acetaminophen | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 22.1 years STANDARD_DEVIATION 2.83 | 21.4 years STANDARD_DEVIATION 3.2 | 23.0 years STANDARD_DEVIATION 4.73 | 22.2 years STANDARD_DEVIATION 3.7 |
| Sex: Female, Male Female | 22 Participants | 23 Participants | 28 Participants | 73 Participants |
| Sex: Female, Male Male | 21 Participants | 16 Participants | 12 Participants | 49 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 | 11 / 43 | 10 / 39 | 13 / 40 |
| serious Total, serious adverse events | 0 / 43 | 0 / 39 | 0 / 40 |
Outcome results
Primary
Sum of Pain Intensity Difference (SPID) Using the Pain Intensity Visual Analog Scale (VAS)
Participants assessed pain intensity on a 100 mm visual analogue scale (VAS) with 0 meaning no pain and 100 meaning the worst pain imaginable. The SPID VAS score for 0 to 12 hours following initial study drug dose measured the cumulative pain intensity difference during treatment with higher mean SPID VAS scores indicating greater improvement from Baseline. The SPID score is a measure of the cumulative pain intensity difference during treatment and the area under the curve was estimated using the linear trapezoidal rule.
Time frame: From time of first study drug administration to 12 hours following first study drug administration
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ABT-712 | Sum of Pain Intensity Difference (SPID) Using the Pain Intensity Visual Analog Scale (VAS) | 268.8 scores on a scale | Standard Error 44.29 |
| Hydrocodone/Acetaminophen | Sum of Pain Intensity Difference (SPID) Using the Pain Intensity Visual Analog Scale (VAS) | 230.9 scores on a scale | Standard Error 47.03 |
| Placebo | Sum of Pain Intensity Difference (SPID) Using the Pain Intensity Visual Analog Scale (VAS) | 54.8 scores on a scale | Standard Error 46.19 |
Secondary
Participants With Adverse Events (AEs)
An adverse event (AE) is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with treatment. If an adverse event meets any of the following criteria, it is considered a serious adverse event (SAE): results in death or is life-threatening, results in admission or prolongation of hospitalization, results in congenital anomaly or persistent or significant disability/incapacity, or is an important medical event requiring medical or surgical intervention to prevent serious outcome. AEs were categorized by severity (mild, moderate, severe) and relationship to treatment (probably, possibly, probably not, not related). Please see Adverse Events section below for more details.
Time frame: AEs were recorded from study drug administration until 30 days following discontinuation of study drug (total 30 days); SAEs were recorded from the time informed consent was obtained until 30 days following discontinuation of study drug (total 51 days).
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-712 | Participants With Adverse Events (AEs) | Death | 0 participants |
| ABT-712 | Participants With Adverse Events (AEs) | Any AE leading to death | 0 participants |
| ABT-712 | Participants With Adverse Events (AEs) | Any AE at least possibly drug related | 5 participants |
| ABT-712 | Participants With Adverse Events (AEs) | Any AE | 14 participants |
| ABT-712 | Participants With Adverse Events (AEs) | Any SAE | 0 participants |
| ABT-712 | Participants With Adverse Events (AEs) | Any AE at least probably not drug related | 9 participants |
| ABT-712 | Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| ABT-712 | Participants With Adverse Events (AEs) | Any severe AE | 1 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Any severe AE | 0 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Any SAE | 0 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Death | 0 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Any AE | 12 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Any AE at least possibly drug related | 8 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Any AE leading to death | 0 participants |
| Hydrocodone/Acetaminophen | Participants With Adverse Events (AEs) | Any AE at least probably not drug related | 4 participants |
| Placebo | Participants With Adverse Events (AEs) | Death | 0 participants |
| Placebo | Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| Placebo | Participants With Adverse Events (AEs) | Any AE leading to death | 0 participants |
| Placebo | Participants With Adverse Events (AEs) | Any AE | 14 participants |
| Placebo | Participants With Adverse Events (AEs) | Any AE at least possibly drug related | 4 participants |
| Placebo | Participants With Adverse Events (AEs) | Any AE at least probably not drug related | 10 participants |
| Placebo | Participants With Adverse Events (AEs) | Any severe AE | 2 participants |
| Placebo | Participants With Adverse Events (AEs) | Any SAE | 0 participants |
Secondary
Time to First Rescue Medication
The median time (minutes) from first dose of study drug to first use of analgesic rescue medication.
Time frame: From time of first study drug administration to 12 hours following first study drug administration
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ABT-712 | Time to First Rescue Medication | 442.0 minutes |
| Hydrocodone/Acetaminophen | Time to First Rescue Medication | 205.0 minutes |
| Placebo | Time to First Rescue Medication | 123.5 minutes |
Secondary
TOTPAR (Total Pain Relief)
TOTPAR was the time-interval weighted sum of pain relief. Pain relief was assessed by participants' responses to how their pain relief was compared with the pain they had just before receiving the first dose of study drug: no relief, a little relief, some relief, a lot of relief, or complete relief. Higher mean TOTPAR scores indicate better pain relief. The TOTPAR score is a measure of the cumulative pain intensity difference during treatment and the area under the curve was estimated using the linear trapezoidal rule.
Time frame: From time of first study drug administration to 12 hours following first study drug administration
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ABT-712 | TOTPAR (Total Pain Relief) | 18.0 scores on a scale | Standard Error 2.06 |
| Hydrocodone/Acetaminophen | TOTPAR (Total Pain Relief) | 15.9 scores on a scale | Standard Error 2.16 |
| Placebo | TOTPAR (Total Pain Relief) | 10.5 scores on a scale | Standard Error 2.13 |