Dental Pain Study of Analgesics in Patients Undergoing Molar Removal

Study Overview
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Brief Summary
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Accessing the efficacy and safety of pregabalin when used alone and in combo with acetaminophen in a dental pain model. To test whether pre-operative dose of pregabalin increases the time to significant post-operative pain (NRS ≥ 5), and hence time to first analgesia consumed post-operatively.

Detailed Description
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This is a 5 arm randomized, double-blind, parallel group, single-center, placebo-controlled study to evaluate the efficacy and safety of pregabalin-acetaminophen combination in the prevention and treatment of post-surgical dental pain in healthy patients. Subjects in every treatment arm will receive a dose 60 min prior to surgery. It is not required to receive a post-operative dose if patient does not feel pain at a scale of NRS≥ 5. Dose 2 will be given post-surgically when patients report at least moderate pain on the categorical scale and a score of ≥5 on 0-10 PI-NRS. Subsequent to dose 2, patients can request rescue analgesic at any time.

Official Title
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Randomized, Double-blind, Parallel Group, Single-center, Placebo-controlled Study to Evaluate Efficacy and Safety of Analgesic Combo in Prevention and Treatment of Post-surgical Dental Pain in Healthy Subjects

Conditions
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Dental Pain

Intervention / Treatment
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* Drug: Pre-Op pregabalin
* Drug: Pre-Op Placebo 1
* Drug: Post-Op pregabalin
* Drug: Post-Op Placebo 1
* Drug: Post-Op Placebo 2
* Drug: Post-Op acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are scheduled to undergo the surgical removal of up to 4 third molars of which at least 2 have to be mandibular molars with a difficulty rating of 4 or 5. Patient must have a negative urine drug screen for drugs of abuse (including tobacco) at screening and at the day of surgery. No alcohol for a minimum of 1 day prior to the surgery. Exclusion Criteria: Patients should not be experiencing oral infections or symptoms of concomitant illness at the time of a scheduled surgery. Patients with a history of any type of malignancy within the past 5 years other than minor skin related cancers. Patients who currently have or have had a history of uncontrolled hypertension. Patients with a known allergy or hypersensitivity to any local anesthetic drug, NSAIDs, gabapentin or pregabalin;. Patients with conditions that affect the absorption, metabolism, or passage of drugs out of the body (e.g., sprue, celiac disease, crohn's disease, etc.)

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Pre-op Placebo 1; Post-op Placebo 1; Post-op Placebo 2 | Drug: Pre-Op Placebo 1<br>* Placebo 1 will be administered 60 min prior to surgery.<br>* Other names: pre-op placebo;Drug: Post-Op Placebo 1<br>* Placebo 1 will be administered post-operatively.<br>Drug: Post-Op Placebo 2<br>* Placebo 2 will be administered post-operatively.<br>|
| Experimental: Group B<br>Pre-op Placebo 1; Post-op Placebo 2; Post-op acetaminophen. | Drug: Pre-Op Placebo 1<br>* Placebo 1 will be administered 60 min prior to surgery.<br>* Other names: pre-op placebo;Drug: Post-Op Placebo 1<br>* Placebo 1 will be administered post-operatively.<br>Drug: Post-Op acetaminophen<br>* Acetaminophen will be administered Post-operatively.<br>|
| Experimental: Group C<br>Pre-op Placebo 1; Post-op pregabalin; Post-op Placebo 2. | Drug: Pre-Op Placebo 1<br>* Placebo 1 will be administered 60 min prior to surgery.<br>* Other names: pre-op placebo;Drug: Post-Op pregabalin<br>* Post-op pregabalin will be administered Post-operatively.<br>Drug: Post-Op Placebo 2<br>* Placebo 2 will be administered post-operatively.<br>|
| Experimental: Group D<br>Pre-op Placebo 1; Post-op pregabalin Post-op acetaminophen. | Drug: Pre-Op Placebo 1<br>* Placebo 1 will be administered 60 min prior to surgery.<br>* Other names: pre-op placebo;Drug: Post-Op pregabalin<br>* Post-op pregabalin will be administered Post-operatively.<br>Drug: Post-Op acetaminophen<br>* Acetaminophen will be administered Post-operatively.<br>|
| Experimental: Group E<br>Pre-op pregabalin; Post-op Placebo 1; Post-op acetaminophen. | Drug: Pre-Op pregabalin<br>* Pre-op pregabalin will be administered 60 min prior to surgery.<br>Drug: Post-Op Placebo 1<br>* Placebo 1 will be administered post-operatively.<br>Drug: Post-Op acetaminophen<br>* Acetaminophen will be administered Post-operatively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum Pain Intensity Difference Scores | Beginning post-surgery (at initiation of Dose 2), Pain Intensity was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = pain as bad as can be). Time weighted sum pain intensity difference scores are reported over 0 to 24 hours. Last observation carried forward method was used. | 0.5, 0.75, 1, 1.25, 1.75, 2.25 hours (± 5 min) and 3.25, 4.25, 5.25, 6.25, 8.25, 10.25, 12.25, 24 hours (± 10 min) | 
| Total Pain Relief Measure | Beginning post-surgery (at initiation of Dose 2), Pain Relief was self-reported over 24 hours, using a pain rating of 0-10 on the Numerical Rating Scale (NRS), with score between 0-10 (0= no pain; 10 = pain as bad as can be). Time-weighted sum pain total pain relief scores over 24 hours is reported Last observation carried forward method was used. | 0.5, 0.75, 1, 1.25, 1.75, 2.25 hours (± 5 min) and 3.25, 4.25, 5.25, 6.25, 8.25, 10.25, 12.25, 24 hours (± 10 min) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Differing Patient Global Evaluation Scores | Patient global evaluation was self-reported at time of first rescue or at 12.25 hours post-surgery, whichever was first, using a 0-4 categorical rating scale of: (0) poor, (1) fair, (2) good, (3) very good, and (4) excellent. The number of participants with differing patient global evaluation scores were reported. | Upto 12.25 hours | 
| Cumulative Number of Participants With Onset of First Perceptible Relief (FPR) Confirmed at 24 Hours After Dose 2 | Beginning post-surgery (at initiation of Dose 2), participants were given a stopwatch and asked to press the stopwatch if and when they feel first perceptible relief; a record of the time was noted in the participants record. Cumulative number of participants with onset of FPR confirmed after dose 2 and was recorded from 0.25 hour till 24 hours after administration of dose 2. | 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24 hours | 
| Cumulative Number of Participants With Onset of Meaning Pain Relief (MPR) Confirmed at 24 Hours After Dose 2 | Beginning post-surgery (at initiation of Dose 2), participants were given a stopwatch and asked to press the stopwatch if and when they feel first perceptible relief; a record of the time was noted in the participants record. Cumulative number of participants with onset of MPR confirmed after dose 2 and was recorded from 0.25 hour till 24 hours after administration of dose 2. | 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24 hours |