Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1940

Study Overview
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Brief Summary
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The primary aim of this study is to investigate if AZD1940 can relieve the pain induced by the surgical removal of one lower wisdom-tooth. This will be done by comparing the effect of AZD1940 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 Randomised, Double Blind, Placebo-Controlled Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1940, in Patients Undergoing Impacted Mandibular Third Molar Extraction

Conditions
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Pain

Intervention / Treatment
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* Drug: AZD1940
* 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. Healthy males or non-fertile females. Exclusion Criteria: History of somatic disease/condition, which may interfere with the objectives of the study, as judged by the investigator. History of previous or ongoing psychiatric disease/condition including psychosis, affective disorder, anxiety disorder, borderline state and personality disorder according to the criteria in the Diagnostic and Statistical Manual of Mental Disorder, 4th edition.

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: AZD1940<br>AZD1940 800ug given predose | Drug: AZD1940<br>* 800ug oral administration<br>|
| Active Comparator: Naproxen<br>Naproxen 500mg given pre-surgery | Drug: Naproxen<br>* 500mg oral administration<br>* Other names: Naprosyn;|
| Placebo Comparator: Placebo<br>Placebo given pre-surgery | Drug: Placebo<br>* Placebo given pre-surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Area Under the Curve 0-8h (AUC0-8h) | Area under the Visual Analogue Scale (VAS, 0-100 mm) time curve 0-8h (from end of surgery). Missing values in the pain-by-time curve was imputated using linear interpolation, last observation carried forward (LOCF) or first observation carried backwards (FOCB) as applicable. | 0-8 h(from end of surgery to 8 hours post surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Area Under the VAS Versus Time Curve 0-4h (AUC0-4h) | Area under the Visual Analogue Scale (VAS, 0-100 mm) time curve 0-4h (from end of surgery). Missing values in the pain-by-time curve was imputated using linear interpolation, last observation carried forward (LOCF) or first observation carried backwards (FOCB) as applicable. | 0-4h (from end of surgery to 4 hours post surgery) | 
| Maximum Pain Based on VAS Scale | Maximum pain recorded on a Visual Analogue Scale, VAS (0-100mm). Observed case. Maximum pain VAS (0-100mm, 0 = no pain - 100 = worst pain imaginable) | From end of surgery to 8h or time first intake of rescue medication (whichever came first) | 
| Mean Pain Based on a VAS Scale | Calculated as the area under the Visual Analogue Pain Scale (0-100 mm) versus time curve divided by time.Missing values in the pain-by-time curve was imputated using linear interpolation, last observation carried forward (LOCF) or first observation carried backwards (FOCB) as applicable. Mean pain VAS (0-100mm, 0 = no pain - 100 = worst pain imaginable) | From end of surgery to 8h or time to first intake of rescue medication (whichever came first) | 
| Pain at Jaw Movement AUC0-8h | Area under the Visual Analogue Scale (VAS, 0-100 mm) of jaw movement versus time curve 0-8h (from end of surgery). Missing values in the pain-by-time curve was imputated using linear interpolation, last observation carried forward (LOCF) or first observation carried backwards (FOCB) as applicable. Area under the curve 0-8h (from end of surgery) of VAS pain at jaw movement (0-100mm, 0 = no pain - 100 = worst pain imaginable) | 0-8h from end of surgery to 8 hours post surgery | 
| Pain at Jaw Movement AUC0-4h | Area under the Visual Analogue Scale (VAS, 0-100 mm) of jaw movement versus time curve 0-4h (from end of surgery). Missing values in the pain-by-time curve was imputated using linear interpolation, last observation carried forward (LOCF) or first observation carried backwards (FOCB) as applicable. Area under the curve 0-4h (from end of surgery) of VAS pain at jaw movement (0-100mm0 = no pain - 100 = worst pain imaginable). | 0-4h after end of surgery to 4 hours post surgery | 
| Maximum Pain at Jaw Movement | Maximum pain at jaw movement recorded on a Visual Analogue Scale, VAS (0-100mm). Observed case. Maximum Pain at jaw movement VAS (0-100mm, 0 = no pain - 100 = worst pain imaginable) | From end of surgery to 8h or time to first intake of rescue medication (whichever came first) | 
| Mean Pain at Jaw Movement | Calculated as the area under the Visual Analogue Pain Scale (0-100 mm) of jaw movement versus time curve divided by time. Missing values in the pain-by-time curve was imputated using linear interpolation, last observation carried forward (LOCF) or first observation carried backwards (FOCB) as applicable. Mean Pain at jaw movement VAS (0-100mm, 0 = no pain - 100 = worst pain imaginable ). | From end of surgery to 8h or time to first intake of rescue medication (whichever came first) | 
| Pain at Rescue Medication | Pain at time of first rescue medication (VAS 0-100mm). Only patients taking rescue are included in analysis. Observed case. Pain at time of first rescue medication (VAS 0-100mm, 0 = no pain - 100 = worst pain imaginable). | At time of first rescue medication taken before 8 hours after end of surgery | 
| Pain at Jaw Movement at Time of First Rescue Medication | Pain at jaw movement at time of first rescue medication (VAS 0-100mm). Observed case. Pain at jaw movement at time of first rescue medication (VAS 0-100mm, 0 = no pain - 100 = worst pain imaginable). | At time of first rescue medication (before 8 hours after end on surgery) | 
| Time to First Intake of Rescue Medication. |  | From end of surgery to 8 hours following surgery | 
| Number of Patients Requesting Rescue Medication | Observed case. | End of surgery up to 8hours following surgery | 
| Maximum Deterioration in Visual Analogue Mood Scale (VAMS) Stimulated | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Maximum Deterioration in VAMS High | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Maximum Deterioration in VAMS Anxious | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Maximum Deterioration in VAMS Sedated | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Maximum Deterioration in VAMS Down | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Time to Max Deterioration in VAMS Stimulated | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Time to Max Deterioration in VAMS High | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Time to Max Deterioration in VAMS Anxious | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Time to Max Deterioration in VAMS Sedated | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 
| Time to Max Deterioration in VAMS Down | Subjective qualities of mood in the subject are measured by letting the subject rate their subjective experiences of a number of adjectives using a series of visual analogue scales. Subjects are required to rate on 100-mm lines the extent to which they felt each adjective at a given time point from 'not at all' on the left end of the scale to 'extremely' on the right end of the scale. The VAMS commonly used in studies with cannabinoids consists of six adjectives and visual analogue scales: stimulated; high (as in drug high, elated); anxious; sedated; down (as in moody, depressed) and hungry. | Between dosing and 12h post-dose | 

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