Trial Outcomes & Findings for Safety and Efficacy Study of XPF-001 to Treat Pain Following Wisdom Tooth Extraction (NCT NCT00954356)

NCT ID: NCT00954356

Last Updated: 2012-07-16

Results Overview

The primary efficacy variable was total pain relief at the 6-hour observation (TOTPAR 6); TOTPAR 6 is an area calculation incorporating time and relief scores over the 6 hours following dosing and was calculated using Simpson's trapezoidal rule. The higher the LS Means scores, the more pain relief was obtained. Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 6 score = 0, maximum possible score = 24

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 61 participants
• Primary outcome timeframe: 6 hours post dose
• Results posted on: 2012-07-16

Participant Flow

All 61 subjects were recruited at a single center between September 29th and November 16th 2009.

Participant milestones

Measure	XPF-001 500 mg XEN402 (5x 100 mg capsules) administered as a single dose	Placebo 5 x matching placebo capsules (administered as a single dose)
Overall Study STARTED	41	20
Overall Study COMPLETED	41	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Study of XPF-001 to Treat Pain Following Wisdom Tooth Extraction

Baseline characteristics by cohort

Measure	XPF-001 n=41 Participants 500 mg XEN402 (5x 100 mg capsules) administered as a single dose	Placebo n=20 Participants 5 x matching placebo capsules (administered as a single dose)	Total n=61 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants	20 Participants n=7 Participants	61 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	20.2 years STANDARD_DEVIATION 2.94 • n=5 Participants	20.9 years STANDARD_DEVIATION 3.01 • n=7 Participants	20.4 years STANDARD_DEVIATION 2.96 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	20 Participants n=7 Participants	61 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants	20 participants n=7 Participants	61 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 hours post dose

Population: Published data from an impacted wisdom tooth removal was used to determine a 60 subject study with 2:1 randomisation and a one-sided significance level of 0.10 would have a power of 84.1%. LOCF was used for imputed values and all subjects were included in both the IIT and PP populations for analysis.

The primary efficacy variable was total pain relief at the 6-hour observation (TOTPAR 6); TOTPAR 6 is an area calculation incorporating time and relief scores over the 6 hours following dosing and was calculated using Simpson's trapezoidal rule.

The higher the LS Means scores, the more pain relief was obtained.

Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 6 score = 0, maximum possible score = 24

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Total Pain Relief at 6 Hours Post Dose (TOTPAR 6)	2.45 units on a scale Interval 0.182 to 4.72	4.37 units on a scale Interval 2.79 to 5.96

SECONDARY outcome

Timeframe: 4 hours

A secondary efficacy variable was total pain relief at the 4-hour observation (TOTPAR 4); TOTPAR 4 is an area calculation incorporating time and relief scores over the 4 hours following dosing and was calculated using Simpson's trapezoidal rule.

The higher the LS Means scores, the more pain relief was obtained.

Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 4 score = 0, maximum possible score = 16).

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Total Pain Relief (TOTPAR) at 4 Hours Post Dose	1.51 units on a scale Interval 0.214 to 2.81	2.44 units on a scale Interval 1.54 to 3.35

SECONDARY outcome

Timeframe: 8 hours

A secondary efficacy variable was total pain relief at the 8-hour observation (TOTPAR 8); TOTPAR 8 is an area calculation incorporating time and relief scores over the 8 hours following dosing and was calculated using Simpson's trapezoidal rule.

The higher the LS Means scores, the more pain relief was obtained.

Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 8 score = 0, maximum possible score = 32

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Total Pain Relief (TOTPAR) at 8 Hours Post Dose	3.43 units on a scale Interval 0.126 to 6.73	6.41 units on a scale Interval 4.11 to 8.71

SECONDARY outcome

Timeframe: 12 hours

A secondary efficacy variable was total pain relief at the 12-hour observation (TOTPAR 12); TOTPAR 12 is an area calculation incorporating time and relief scores over the 12 hours following dosing and was calculated using Simpson's trapezoidal rule.

The higher the LS Means scores, the more pain relief was obtained.

Relief (REL) scores were measured at multiple timepoints after dosing, using a 5 point categorical pain relief rating scale. (None = 0, A Little Relief = 1, Some = 2, A Lot = 3, Complete Relief = 4). The minimum possible TOTPAR 12 score = 0, maximum possible score = 48.

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Total Pain Relief (TOTPAR) at 12 Hours Post Dose	5.42 units on a scale Interval -0.019 to 10.9	10.7 units on a scale Interval 6.93 to 14.5

SECONDARY outcome

Timeframe: Baseline to 4 hours post dose

Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score).

SPID4 is an area calculation encompassing time and the PID scores over the 4 hours following dosing. The minimum possible SPID4 value = -40, the maximum possible = 40.

A positive SPID LS Means score implies reduced pain intensity over the corresponding time period.

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Summed Pain Intensity Difference (SPID) at 4 Hours Post Dose	-0.577 units on a scale Interval -3.55 to 2.39	0.364 units on a scale Interval -1.71 to 2.43

SECONDARY outcome

Timeframe: Baseline to 6 hours post dose

Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score).

SPID6 is an area calculation encompassing time and the PID scores over the 6 hours following dosing. The minimum possible SPID6 value = -60, the maximum possible = 60.

A positive SPID LS Means score implies reduced pain intensity over the corresponding time period.

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Summed Pain Intensity Difference (SPID) at 6 Hours Post Dose	-0.811 units on a scale Interval -5.89 to 4.26	1.48 units on a scale Interval -2.06 to 5.02

SECONDARY outcome

Timeframe: Baseline to 8 hours post dose

Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score).

SPID8 is an area calculation encompassing time and the PID scores over the 8 hours following dosing. The minimum possible SPID8 value = -80, the maximum possible = 80.

A positive SPID LS Means score implies reduced pain intensity over the corresponding time period.

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Summed Pain Intensity Difference (SPID) at 8 Hours Post Dose	-0.958 units on a scale Interval -8.24 to 6.33	2.77 units on a scale Interval -2.31 to 7.85

SECONDARY outcome

Timeframe: Baseline to 12 hours post dose

Pain intensity was scored on an 11-point scale (PINRS), (0=no pain - 10=pain as bad as you can imagine). Scores were measured at baseline (after surgery but before dosing) and at multiple timepoints after dosing. At each timepoint, pain intensity difference (PID) was calculated (ie, baseline score minus timepoint score).

SPID12 is an area calculation encompassing time and the PID scores over the 12 hours following dosing. The minimum possible SPID12 value = -120, the maximum possible = 120.

A positive SPID LS Means score implies reduced pain intensity over the corresponding time period.

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Summed Pain Intensity Difference (SPID) at 12 Hours Post Dose	-1.10 units on a scale Interval -13.0 to 10.8	5.68 units on a scale Interval -2.6 to 14.0

SECONDARY outcome

Timeframe: 24 hours

Onset of analgesia was measured using 2 stopwatches. Both stopwatches were started at the time of dose administration. Stopwatch 1 was pressed by the subject when any pain relief was first perceived (Time to First Perceptible Relief) and stopwatch 2 was pressed by the subject when pain relief became meaningful (Time to Meaningful Relief).

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Time to First Perceptible Relief	NA Minutes Interval 37.0 to Data not estimable as less than 50% of subject reported perceptible relief. A minimum of 50% of subjects are required to report the event in order to calculate the median.	NA Minutes Interval 59.0 to Data not estimable as less than 50% of subject reported perceptible relief. A minimum of 50% of subjects are required to report the event in order to calculate the median.

SECONDARY outcome

Timeframe: 24 hours

Onset of analgesia was measured using 2 stopwatches. Both stopwatches were started at the time of dose administration. Stopwatch 1 was pressed by the subject when any pain relief was first perceived (Time to First Perceptible Relief) and stopwatch 2 was pressed by the subject when pain relief became meaningful (Time to Meaningful Relief).

'Meaningful Relief' was defined as when the relief became 'meaningful' to each individual subject, and was not necessarily a complete absence of pain. 'Meaningful Relief' could not occur before 'First Perceptible Relief'.

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Time to Meaningful Relief	NA Minutes Data not estimable as less than 50% of subject reported meaningful relief. A minimum of 50% of subjects are required to report the event in order to calculate the median.	NA Minutes Data not estimable as less than 50% of subject reported meaningful relief. A minimum of 50% of subjects are required to report the event in order to calculate the median.

SECONDARY outcome

Timeframe: 24 hours

The time of administration of rescue medication (if any) was recorded for each subject and the duration since dosing was calculated.

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Time to Rescue Medication	93 Minutes Interval 73.0 to 153.0	133 Minutes Interval 103.0 to The upper limit of the 95% confidence interval is not calculable from the available data.

SECONDARY outcome

Timeframe: 48 hours

Adverse Events were recorded at the time of occurence. Clinically significant findings (if any) in ECG and vital signs assessments and laboratory samples were recorded as adverse events.

Treatment Emergent Adverse Events (TEAEs) are those which either started or worsened following administration of study drug (XPF-001 or placebo).

Outcome measures

Measure	Placebo n=20 Participants Subjects received a single dose of placebo after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.	XPF-001 n=41 Participants Subjects received a single dose of XPF-001 500 mg after reaching moderate pain on a numerical rating scale following surgical extraction of 2 or more impacted third molars, of which at least 1 was a partial or full bony mandibular impaction.
Treatment Emergent Adverse Events	7 Events	35 Events

Adverse Events

XPF-001

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	XPF-001 n=41 participants at risk 500 mg XEN402 (5x 100 mg capsules) administered as a single dose	Placebo n=20 participants at risk 5 x matching placebo capsules (administered as a single dose)
Nervous system disorders Dizziness	17.1% 7/41	0.00% 0/20
Nervous system disorders Somnolence	7.3% 3/41	5.0% 1/20
Gastrointestinal disorders Nausea	19.5% 8/41	10.0% 2/20
Investigations Neutrophil count increased	0.00% 0/41	5.0% 1/20
Investigations White blood cell count increased	0.00% 0/41	5.0% 1/20
Psychiatric disorders Confusional State	7.3% 3/41	0.00% 0/20
Nervous system disorders Headache	9.8% 4/41	5.0% 1/20

Additional Information

Vice President Clinical

Xenon Pharmaceuticals Inc.

Phone: 6044843300

Email: pgoldberg@xenon-pharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60