Pain
Conditions
Keywords
Analgesic effect
Brief summary
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.
Interventions
DRUGAZD1386
95mg, oral solution, single dose
DRUGNaproxen
500mg, capsule, single dose
DRUGPlacebo
AZD1386 Placebo oral solution
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference in Percent (SPID%) | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 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. | 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. |
| Time to First Perceptible Pain Relief | 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 | 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. |
| Time to First Meaningful Pain Relief | 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 | 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. |
| VAS Pain Intensity at Rescue Intake | at the time of first administration of rescue analgesic, up to the maximum time of 8 hours after intake of the investigational product | 0 = 'No pain' 100 ='Worst pain imaginable' |
| VAS Pain on Jaw Movement at Rescue Intake | at the time of first administration of rescue analgesic, up to the maximum time of 8 hours after intake of the investigational product | 0 = 'No pain' 100 ='Worst pain imaginable' |
Countries
United States
Participant flow
Recruitment details
The study was performed at Lifetree Clinical Research, Salt Lake City, USA, during April-June 2008. 135 participants enrolled in the study, 103 randomized and 99 patients completed the study.
Pre-assignment details
Screening for eligibility prior to the residential day, and selecting the patients that request pain relief, due to pain from the dental surgical area, within 6 hours after the end of the administration of the local anaesthetic.
Participants by arm
| Arm | Count |
|---|---|
| AZD1386 AZD1386 95 mg oral solution | 40 |
| Naproxen Naproxen 500 mg capsule | 23 |
| Placebo AZD1386 Placebo oral solution | 40 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | AZD1386 | Naproxen | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 21.5 year STANDARD_DEVIATION 4.4 | 21 year STANDARD_DEVIATION 4.8 | 21.9 year STANDARD_DEVIATION 4.8 | 21.5 year STANDARD_DEVIATION 4.6 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 23 Participants | 40 Participants | 103 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 | 4 / 40 | 0 / 23 | 6 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 23 | 0 / 40 |
Outcome results
Primary
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).
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD1386 | Sum of Pain Intensity Difference in Percent (SPID%) | 35.5 percentage of pain intensity change * h |
| Naproxen | Sum of Pain Intensity Difference in Percent (SPID%) | 171.8 percentage of pain intensity change * h |
| Placebo | Sum of Pain Intensity Difference in Percent (SPID%) | -7.5 percentage of pain intensity change * h |
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour | 31.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 15 minutes | 33 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 30 minutes | 30.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 45 minutes | 28.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | Just before dosing | 50 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 15 minutes | 35.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 30 minutes | 41 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 45 minutes | 50.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 2 hours | 50.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 2 hours 30 minutes | 30.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 3 hours | 24.5 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 4 hours | 14 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 5 hours | 19 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 6 hours | 14 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 7 hours | 15 units on VAS scale |
| AZD1386 | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 8 hours | 14 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 15 minutes | 46 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 30 minutes | 38 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 45 minutes | 35 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 6 hours | 7 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 2 hours | 28 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 2 hours 30 minutes | 26 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 8 hours | 4 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 3 hours | 21 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | Just before dosing | 48 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 7 hours | 6 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 15 minutes | 54 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 4 hours | 18 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 30 minutes | 61 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 45 minutes | 61 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour | 52 units on VAS scale |
| Naproxen | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 5 hours | 10 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 3 hours | 20 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 15 minutes | 53 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 5 hours | 14 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 30 minutes | 47 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 30 minutes | 44 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 8 hours | 11.5 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | Just before dosing | 46.5 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour 45 minutes | 50 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 4 hours | 14.5 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 1 hour | 55 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 2 hours | 37 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 6 hours | 13 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 15 minutes | 45 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 2 hours 30 minutes | 23 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 45 minutes | 51 units on VAS scale |
| Placebo | Pain Intensity (PI) by Using Visual Analogue Scale (VAS) (0-100 mm) | 7 hours | 14 units on VAS scale |
Secondary
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD1386 | Time to First Meaningful Pain Relief | 8.0 hour |
| Naproxen | Time to First Meaningful Pain Relief | 4.2 hour |
| Placebo | Time to First Meaningful Pain Relief | 8.0 hour |
Secondary
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.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD1386 | Time to First Perceptible Pain Relief | 0.3 hour |
| Naproxen | Time to First Perceptible Pain Relief | 0.8 hour |
| Placebo | Time to First Perceptible Pain Relief | 1.3 hour |
Secondary
VAS Pain Intensity at Rescue Intake
0 = 'No pain' 100 ='Worst pain imaginable'
Time frame: at the time of first administration of rescue analgesic, up to the maximum time of 8 hours after intake of the investigational product
Population: Only participants that took rescue medication are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD1386 | VAS Pain Intensity at Rescue Intake | 61.0 units on a VAS scale |
| Naproxen | VAS Pain Intensity at Rescue Intake | 69.0 units on a VAS scale |
| Placebo | VAS Pain Intensity at Rescue Intake | 70.5 units on a VAS scale |
Secondary
VAS Pain on Jaw Movement at Rescue Intake
0 = 'No pain' 100 ='Worst pain imaginable'
Time frame: at the time of first administration of rescue analgesic, up to the maximum time of 8 hours after intake of the investigational product
Population: Only participants that took rescue medication are included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD1386 | VAS Pain on Jaw Movement at Rescue Intake | 65.0 Units on a VAS scale |
| Naproxen | VAS Pain on Jaw Movement at Rescue Intake | 81.0 Units on a VAS scale |
| Placebo | VAS Pain on Jaw Movement at Rescue Intake | 73.5 Units on a VAS scale |