Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1386

Study Overview
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Brief Summary
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The primary aim of this study is to investigate if AZD1386 can relieve the pain induced by the surgical removal of one lower wisdom-tooth. This will be done by comparing the effect of AZD1386 to placebo (inactive substance) on pain. A number of patients will instead receive the common painkiller naproxen for comparison purposes. Rescue medication, acetaminophen, will be allowed if a need for additional painkillers would arise. A number of patients will receive naproxen as control.

Official Title
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A Double-blind, Randomized, Placebo and Naproxen Controlled Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1386, in Patients Undergoing Impacted Mandibular Third Molar Extraction

Conditions
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Pain

Intervention / Treatment
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* Drug: AZD1386
* Drug: Naproxen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for surgical removal of one partial or complete impacted mandibular third molar. Provision of signed informed consent. Exclusion Criteria: History of somatic disease/condition, which may interfere with the objectives for the study, as judged by the investigator. Clinically significant illness or clinically relevant trauma within the 2 weeks prior to the administration of the investigational product, as judged by the investigator. A family history of short QT syndrome (SQTS) or sudden cardiac death (SCD) amongst first degree relatives Patients with a body temperature >37.5°C at Visit 2, before start of surgical procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD1386<br> | Drug: AZD1386<br>* 95mg, oral solution, single dose<br>|
| Active Comparator: Naproxen<br> | Drug: Naproxen<br>* 500mg, capsule, single dose<br>|
| Placebo Comparator: Placebo<br>Placebo matching AZD1386 | Drug: Placebo<br>* AZD1386 Placebo oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference in Percent (SPID%) | Weighted sum of the pain intensity (PI) differences in percent for the given time frame. PI values are weighted according to the time since the previous PI assessment (or the time of administration of the investigational product for the first post-dose assessment). SPID% = elapsed since previous value, where is the PI difference in percent at assessment t. High values=good effect, low values=poor effect Pointwise assessments of pain are measured using a VAS scale (0-100 mm), as described in the secondary outcome measure (PI). | from the start of administration of the investigational product up to the time of first administration of rescue analgesic or up to a maximum of 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 0 = 'No pain' 100 ='Worst pain imaginable' Up to 16 individual assessments were performed and contained in the derived primary outcome measure, thus not reported separately. | Immediately prior to administration of investigational product (IP). After intake of IP assessment will be made every 15 min for the first 2 h, at 2h and 30 min, 3 h and thereafter every hour up to 8 h after intake of IP. | 
| Time to First Perceptible Pain Relief | First perceptible pain relief is the time at which the participant begins to feel any pain relief at all. The time to first perceptible pain relief was reported by the participant using a stopwatch. Each time the watch is stopped, the participants will rate their pain intensity. Note: Participants who do not report first perceptible pain relief, and participants who report first perceptible pain relief after rescue intake, have the corresponding time censored to 8 hours. | from the start of administration of the investigational product up to the time of first administration of rescue analgesic or up to a maximum of 8 hours | 
| Time to First Meaningful Pain Relief | First meaningful pain relief is the time when the participant's pain relief feels meaningful. The time to first meaningful pain relief will be reported by the participant using a stopwatch. Each time the watch is stopped, the participants will rate their pain intensity. Note: Participants who do not report first meaningful pain relief, and participants who report first meaningful pain relief after rescue intake, have the corresponding time censored to 8 hours. | from the start of administration of the investigational product up to the time of first administration of rescue analgesic or up to a maximum of 8 hours | 
| VAS Pain Intensity at Rescue Intake | 0 = 'No pain' 100 ='Worst pain imaginable' | at the time of first administration of rescue analgesic, up to the maximum time of 8 hours after intake of the investigational product | 
| VAS Pain on Jaw Movement at Rescue Intake | 0 = 'No pain' 100 ='Worst pain imaginable' | at the time of first administration of rescue analgesic, up to the maximum time of 8 hours after intake of the investigational product | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Analgesic effect