Hydrocodone/Acetaminophen for Acute Pain Following Third Molar Tooth Extraction

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Randomized, Multicenter, Single-blind, Placebo-controlled Study Comparing the Analgesic Efficacy and Safety of Hydrocodone/ Acetaminophen Extended-release Tablets and Hydrocodone/Acetaminophen (NORCO) to Placebo in Subjects With Acute Pain Following Third Molar Tooth Extraction

Conditions
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Pain

Intervention / Treatment
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* Drug: ABT-712 Extended-release
* Drug: Hydrocodone/Acetaminophen Immediate-release
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-712<br>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). | Drug: ABT-712 Extended-release<br>* ABT-712 extended-release tablet<br>* Other names: Hydrocodone bitartrate and acetaminophen extended-release;Drug: Placebo<br>* Placebo tablet<br>|
| Active Comparator: Hydrocodone/Acetaminophen<br>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). | Drug: Hydrocodone/Acetaminophen Immediate-release<br>* Hydrocodone/acetaminophen immediate-release tablet<br>Drug: Placebo<br>* Placebo tablet<br>|
| Placebo Comparator: Placebo<br>2 doses of 2 placebo tablets, administered once every 6 hours for 12 hours (for a total of 2 doses). | Drug: Placebo<br>* Placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From time of first study drug administration to 12 hours following first study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From time of first study drug administration to 12 hours following first study drug administration | 
| Time to First Rescue Medication | The median time (minutes) from first dose of study drug to first use of analgesic rescue medication. | From time of first study drug administration to 12 hours following first study drug administration | 
| 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. | 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). |