Trial Outcomes & Findings for Study to Investigate the Analgesic Efficacy of a Single Dose of AZD1940 (NCT NCT00659490)

NCT ID: NCT00659490

Last Updated: 2012-06-11

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 151 participants
• Primary outcome timeframe: 0-8 h(from end of surgery to 8 hours post surgery)
• Results posted on: 2012-06-11

Participant Flow

1 centre (Lifetree Clinical Research, Salt Lake City, Utah, USA) recruited between Feb and May 2008

Screening for eligibility

Participant milestones

Measure	AZD1940 AZD1940 800ug given predose	Placebo Placebo given pre-surgery	Naproxen Naproxen 500mg given pre-surgery
Overall Study STARTED	61	59	31
Overall Study COMPLETED	59	59	30
Overall Study NOT COMPLETED	2	0	1

Reasons for withdrawal

Measure	AZD1940 AZD1940 800ug given predose	Placebo Placebo given pre-surgery	Naproxen Naproxen 500mg given pre-surgery
Overall Study Lost to Follow-up	2	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery	Total n=151 Participants Total of all reporting groups
Age Continuous	20.6 Years n=5 Participants	21.0 Years n=7 Participants	20.5 Years n=5 Participants	20.7 Years n=4 Participants
Sex/Gender, Customized Unknown	61 Participants n=5 Participants	59 Participants n=7 Participants	31 Participants n=5 Participants	151 Participants n=4 Participants

PRIMARY outcome

Timeframe: 0-8 h(from end of surgery to 8 hours post surgery)

Population: The analyses based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Pain Area Under the Curve 0-8h (AUC0-8h)	355 mm*h Standard Deviation 182.3	356 mm*h Standard Deviation 165.7	129 mm*h Standard Deviation 105.4

SECONDARY outcome

Timeframe: 0-4h (from end of surgery to 4 hours post surgery)

Population: The analyses based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Pain Area Under the VAS Versus Time Curve 0-4h (AUC0-4h)	145 mm*h Standard Deviation 93.5	143 mm*h Standard Deviation 81.7	54 mm*h Standard Deviation 45.0

SECONDARY outcome

Timeframe: From end of surgery to 8h or time first intake of rescue medication (whichever came first)

Population: The analyses based on a per-protocol population.

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)

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Maximum Pain Based on VAS Scale	66 mm Standard Deviation 24.5	65 mm Standard Deviation 23.7	33 mm Standard Deviation 20.7

SECONDARY outcome

Timeframe: From end of surgery to 8h or time to first intake of rescue medication (whichever came first)

Population: The analyses based on a per-protocol population.

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)

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Mean Pain Based on a VAS Scale	31 mm Standard Deviation 19.0	29 mm Standard Deviation 16.7	13 mm Standard Deviation 10.6

SECONDARY outcome

Timeframe: 0-8h from end of surgery to 8 hours post surgery

Population: The analyses based on a per-protocol pop.

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)

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Pain at Jaw Movement AUC0-8h	342 mm*h Standard Deviation 192.0	337 mm*h Standard Deviation 170.5	135 mm*h Standard Deviation 119.7

SECONDARY outcome

Timeframe: 0-4h after end of surgery to 4 hours post surgery

Population: The analyses based on a per-protocol pop.

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).

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Pain at Jaw Movement AUC0-4h	142 mm*h Standard Deviation 100.3	138 mm*h Standard Deviation 86.9	53 mm*h Standard Deviation 47.5

SECONDARY outcome

Timeframe: From end of surgery to 8h or time to first intake of rescue medication (whichever came first)

Population: The analyses based on a per-protocol population.

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)

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Maximum Pain at Jaw Movement	63 mm Standard Deviation 25.2	63 mm Standard Deviation 25.5	33 mm Standard Deviation 24.7

SECONDARY outcome

Timeframe: From end of surgery to 8h or time to first intake of rescue medication (whichever came first)

Population: The analyses based on a per-protocol population.

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 ).

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Mean Pain at Jaw Movement	32 mm Standard Deviation 20.9	28 mm Standard Deviation 16.9	14 mm Standard Deviation 12.4

SECONDARY outcome

Timeframe: At time of first rescue medication taken before 8 hours after end of surgery

Population: Only patients taking rescue are included in analysis. The analyses are based on a per-protocol population.

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).

Outcome measures

Measure	AZD1940 n=37 Participants AZD1940 800ug given predose	Placebo n=43 Participants Placebo given pre-surgery	Naproxen n=7 Participants Naproxen 500mg given pre-surgery
Pain at Rescue Medication	73 mm Standard Deviation 20.6	70 mm Standard Deviation 20.5	47 mm Standard Deviation 13.8

SECONDARY outcome

Timeframe: At time of first rescue medication (before 8 hours after end on surgery)

Population: Only patients taking rescue are included in analysis. The analyses are based on a per-protocol population.

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).

Outcome measures

Measure	AZD1940 n=37 Participants AZD1940 800ug given predose	Placebo n=43 Participants Placebo given pre-surgery	Naproxen n=7 Participants Naproxen 500mg given pre-surgery
Pain at Jaw Movement at Time of First Rescue Medication	67 mm Standard Deviation 26.2	65 mm Standard Deviation 25.5	53 mm Standard Deviation 15.4

SECONDARY outcome

Timeframe: From end of surgery to 8 hours following surgery

Population: Only patients actually taking rescue medication are included in analysis.

Outcome measures

Measure	AZD1940 n=37 Participants AZD1940 800ug given predose	Placebo n=43 Participants Placebo given pre-surgery	Naproxen n=7 Participants Naproxen 500mg given pre-surgery
Time to First Intake of Rescue Medication.	3.8 Hours Standard Deviation 1.05	3.7 Hours Standard Deviation 1.16	4.7 Hours Standard Deviation 1.18

SECONDARY outcome

Timeframe: End of surgery up to 8hours following surgery

Population: The analyses are based on a per-protocol population.

Observed case.

Outcome measures

Measure	AZD1940 n=61 Participants AZD1940 800ug given predose	Placebo n=59 Participants Placebo given pre-surgery	Naproxen n=31 Participants Naproxen 500mg given pre-surgery
Number of Patients Requesting Rescue Medication	37 Participants	43 Participants	7 Participants

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=41 Participants AZD1940 800ug given predose	Placebo n=12 Participants Placebo given pre-surgery	Naproxen n=28 Participants Naproxen 500mg given pre-surgery
Maximum Deterioration in Visual Analogue Mood Scale (VAMS) Stimulated	22 mm Standard Deviation 15.1	26 mm Standard Deviation 23.9	28 mm Standard Deviation 22.7

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=41 Participants AZD1940 800ug given predose	Placebo n=16 Participants Placebo given pre-surgery	Naproxen n=10 Participants Naproxen 500mg given pre-surgery
Maximum Deterioration in VAMS High	30 mm Standard Deviation 25.2	12 mm Standard Deviation 7.5	20 mm Standard Deviation 22.8

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=35 Participants AZD1940 800ug given predose	Placebo n=27 Participants Placebo given pre-surgery	Naproxen n=13 Participants Naproxen 500mg given pre-surgery
Maximum Deterioration in VAMS Anxious	20 mm Standard Deviation 20.0	15 mm Standard Deviation 13.1	13 mm Standard Deviation 15.1

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=53 Participants AZD1940 800ug given predose	Placebo n=33 Participants Placebo given pre-surgery	Naproxen n=12 Participants Naproxen 500mg given pre-surgery
Maximum Deterioration in VAMS Sedated	33 mm Standard Deviation 24.8	21 mm Standard Deviation 19.2	24 mm Standard Deviation 26.4

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included. The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=32 Participants AZD1940 800ug given predose	Placebo n=22 Participants Placebo given pre-surgery	Naproxen n=8 Participants Naproxen 500mg given pre-surgery
Maximum Deterioration in VAMS Down	20 mm Standard Deviation 20.4	25 mm Standard Deviation 23.5	24 mm Standard Deviation 29.0

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=41 Participants AZD1940 800ug given predose	Placebo n=28 Participants Placebo given pre-surgery	Naproxen n=12 Participants Naproxen 500mg given pre-surgery
Time to Max Deterioration in VAMS Stimulated	143 Minutes Standard Deviation 94.9	163 Minutes Standard Deviation 108	213 Minutes Standard Deviation 190

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=41 Participants AZD1940 800ug given predose	Placebo n=16 Participants Placebo given pre-surgery	Naproxen n=10 Participants Naproxen 500mg given pre-surgery
Time to Max Deterioration in VAMS High	115 minutes Standard Deviation 56.7	191 minutes Standard Deviation 180.0	193 minutes Standard Deviation 125.9

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=35 Participants AZD1940 800ug given predose	Placebo n=27 Participants Placebo given pre-surgery	Naproxen n=13 Participants Naproxen 500mg given pre-surgery
Time to Max Deterioration in VAMS Anxious	126 minutes Standard Deviation 88.0	167 minutes Standard Deviation 115.7	212 minutes Standard Deviation 207.2

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=53 Participants AZD1940 800ug given predose	Placebo n=33 Participants Placebo given pre-surgery	Naproxen n=12 Participants Naproxen 500mg given pre-surgery
Time to Max Deterioration in VAMS Sedated	190 minutes Standard Deviation 134.7	221 minutes Standard Deviation 134.5	227 minutes Standard Deviation 150.5

SECONDARY outcome

Timeframe: Between dosing and 12h post-dose

Population: Only patients reporting a deterioration are included.The analyses are based on a per-protocol population.

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.

Outcome measures

Measure	AZD1940 n=32 Participants AZD1940 800ug given predose	Placebo n=22 Participants Placebo given pre-surgery	Naproxen n=8 Participants Naproxen 500mg given pre-surgery
Time to Max Deterioration in VAMS Down	227 minutes Standard Deviation 156.2	262 minutes Standard Deviation 106.3	349 minutes Standard Deviation 243.3

Adverse Events

AZD1940

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Naproxen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AZD1940 n=61 participants at risk AZD1940 800ug given predose	Placebo n=59 participants at risk Placebo given pre-surgery	Naproxen n=31 participants at risk Naproxen 500mg given pre-surgery
Nervous system disorders Presyncope, Syncope	4.9% 3/61	3.4% 2/59	0.00% 0/31

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee AstraZeneca has exclusive rights to publish the results of the tudy
• Publication restrictions are in place

Restriction type: OTHER