Trial Outcomes & Findings for A Crossover Study to Evaluate the Safety, Tolerability and Efficacy of XPF-002 in Subjects With Postherpetic Neuralgia (PHN) (NCT NCT01195636)

NCT ID: NCT01195636

Last Updated: 2013-11-25

Results Overview

Subjects recorded their pain scores 4 times each day (using an 11-point Likert numerical rating scale (NRS); 0-10, where 0 = no pain and 10 = worst pain imaginable). An average (mean) daily pain score was calculated. This measurement is the 'Change in mean daily pain score from baseline between the 3rd week of XPF-002 treatment and the 3rd week of placebo treatment for each subject'. Any missing mean daily pain scores were imputed using last observation carried forward (LOCF). The reduction in pain on each treatment compared to baseline is reported as a negative number. A larger negative number, indicates a greater reduction in pain. (A positive number would indicate pain was increased compared to baseline.)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 70 participants
• Primary outcome timeframe: 3 weeks
• Results posted on: 2013-11-25

Participant Flow

Participant milestones

Measure	XPF-002 First, Then Placebo In the first intervention period XPF-002 ointment (8% strength) was applied twice daily for 3 weeks. After a washout period, Placebo ointment was applied twice daily for 3 weeks in the second intervention period.	Placebo First, Then XPF-002 In the first intervention period Placebo ointment was applied twice daily for 3 weeks. After a washout period, XPF-002 ointment (8% strength) was applied twice daily for 3 weeks in the second intervention period.
First Intervention (3 Weeks) STARTED	35	35
First Intervention (3 Weeks) Received at Least 1 Dose of Drug	33	35
First Intervention (3 Weeks) COMPLETED	30	32
First Intervention (3 Weeks) NOT COMPLETED	5	3
Washout Period (2 Weeks) STARTED	30	32
Washout Period (2 Weeks) COMPLETED	28	29
Washout Period (2 Weeks) NOT COMPLETED	2	3
Second Intervention (3 Weeks) STARTED	28	29
Second Intervention (3 Weeks) COMPLETED	27	27
Second Intervention (3 Weeks) NOT COMPLETED	1	2

Reasons for withdrawal

Measure	XPF-002 First, Then Placebo In the first intervention period XPF-002 ointment (8% strength) was applied twice daily for 3 weeks. After a washout period, Placebo ointment was applied twice daily for 3 weeks in the second intervention period.	Placebo First, Then XPF-002 In the first intervention period Placebo ointment was applied twice daily for 3 weeks. After a washout period, XPF-002 ointment (8% strength) was applied twice daily for 3 weeks in the second intervention period.
First Intervention (3 Weeks) Adverse Event	2	3
First Intervention (3 Weeks) Protocol Violation	1	0
First Intervention (3 Weeks) Withdrawal by Subject	1	0
First Intervention (3 Weeks) Lost to Follow-up	1	0
Washout Period (2 Weeks) Adverse Event	1	1
Washout Period (2 Weeks) Withdrawal by Subject	1	2
Second Intervention (3 Weeks) Adverse Event	1	1
Second Intervention (3 Weeks) Withdrawal by Subject	0	1

Baseline Characteristics

A Crossover Study to Evaluate the Safety, Tolerability and Efficacy of XPF-002 in Subjects With Postherpetic Neuralgia (PHN)

Baseline characteristics by cohort

Measure	XPF-002 First, Then Placebo n=35 Participants XPF-002 ointment applied twice daily for 3 weeks followed by Placebo ointment applied twice daily for 3 weeks (after a washout period)	Placebo First, Then XPF-002 n=35 Participants Placebo ointment applied twice daily for 3 weeks followed by XPF-002 ointment applied twice daily for 3 weeks (after a washout period)	Total n=70 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants	18 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Age Continuous	58.3 years STANDARD_DEVIATION 13.58 • n=5 Participants	63.1 years STANDARD_DEVIATION 9.73 • n=7 Participants	60.7 years STANDARD_DEVIATION 11.98 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants	35 participants n=7 Participants	70 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 weeks

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. The maximum number of subjects who could contribute to this population is 57. Last Observation Carried Forward (LOCF) was used to impute any missing data.

Subjects recorded their pain scores 4 times each day (using an 11-point Likert numerical rating scale (NRS); 0-10, where 0 = no pain and 10 = worst pain imaginable). An average (mean) daily pain score was calculated.

This measurement is the 'Change in mean daily pain score from baseline between the 3rd week of XPF-002 treatment and the 3rd week of placebo treatment for each subject'. Any missing mean daily pain scores were imputed using last observation carried forward (LOCF).

The reduction in pain on each treatment compared to baseline is reported as a negative number. A larger negative number, indicates a greater reduction in pain. (A positive number would indicate pain was increased compared to baseline.)

Outcome measures

Measure	XPF-002 n=56 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=56 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Change in Mean Daily Pain Score From Baseline to Week 3 (With LOCF)	-0.94 units on a scale Interval -1.3 to -0.58	-0.97 units on a scale Interval -1.33 to -0.61

SECONDARY outcome

Timeframe: 1 week

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. Missing data were not imputed. Only subjects who recorded sufficient pain scores in each treatment period were included in this analysis.

Subjects recorded their pain scores 4 times each day (using an 11-point Likert numerical rating scale (NRS); 0-10, where 0 = no pain and 10 = worst pain imaginable). An average (mean) daily pain score was calculated.

This measurement is the 'Change in mean daily pain score from baseline between the 1st week of XPF-002 treatment and the 1st week of placebo treatment for each subject'. Missing data were not imputed.

The reduction in pain on each treatment compared to baseline is reported as a negative number. A larger negative number, indicates a greater reduction in pain. (A positive number would indicate pain was increased compared to baseline.)

Outcome measures

Measure	XPF-002 n=54 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=54 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Change in Mean Daily Pain Score From Baseline to Week 1	-0.42 units on a scale Interval -0.73 to -0.11	-0.55 units on a scale Interval -0.86 to -0.24

SECONDARY outcome

Timeframe: 2 week

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. Missing data were not imputed. Only subjects who recorded sufficient pain scores in each treatment period were included in this analysis.

Subjects recorded their pain scores 4 times each day (using an 11-point Likert numerical rating scale (NRS); 0-10, where 0 = no pain and 10 = worst pain imaginable). An average (mean) daily pain score was calculated.

This measurement is the 'Change in mean daily pain score from baseline between the 2nd week of XPF-002 treatment and the 2nd week of placebo treatment for each subject'. Missing data were not imputed.

The reduction in pain on each treatment compared to baseline is reported as a negative number. A larger negative number, indicates a greater reduction in pain. (A positive number would indicate pain was increased compared to baseline.)

Outcome measures

Measure	XPF-002 n=55 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=55 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Change in Mean Daily Pain Score From Baseline to Week 2	-0.74 units on a scale Interval -1.07 to -0.41	-0.70 units on a scale Interval -1.03 to -0.37

SECONDARY outcome

Timeframe: 3 Weeks

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. Missing data were not imputed. Only subjects who recorded sufficient pain scores in each treatment period were included in this analysis.

Subjects recorded their pain scores 4 times each day (using an 11-point Likert numerical rating scale (NRS); 0-10, where 0 = no pain and 10 = worst pain imaginable). An average (mean) daily pain score was calculated.

This measurement is the 'Change in mean daily pain score from baseline between the 3rd week of XPF-002 treatment and the 3rd week of placebo treatment for each subject'. Missing data were not imputed.

The reduction in pain on each treatment compared to baseline is reported as a negative number. A larger negative number, indicates a greater reduction in pain. (A positive number would indicate pain was increased compared to baseline.)

Outcome measures

Measure	XPF-002 n=52 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=52 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Change in Mean Daily Pain Score From Baseline to Week 3	-0.96 units on a scale Interval -1.33 to -0.58	-0.96 units on a scale Interval -1.34 to -0.59

SECONDARY outcome

Timeframe: 3 Weeks

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. Missing data were not imputed. Only subjects who recorded sufficient pain scores in each treatment period were included in this analysis.

Subjects recorded their pain scores 4 times each day (using an 11-point Likert numerical rating scale (NRS); 0-10, where 0 = no pain and 10 = worst pain imaginable). An average (mean) daily pain score was calculated.

Outcome measures

Measure	XPF-002 n=52 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=52 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Proportion of Subjects Achieving at Least a 1 Point Improvement in Mean Daily Pain Score (Measured Using the 11-point Likert NRS) From Baseline to Week 3 on XPF-002 Compared to Placebo	22 participants	19 participants

SECONDARY outcome

Timeframe: 3 weeks

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. Missing data were not imputed. Only subjects who recorded sufficient pain scores in each treatment period were included in this analysis.

Outcome measures

Measure	XPF-002 n=52 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=52 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Proportion of Subjects Achieving 50% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment	15 participants	6 participants

SECONDARY outcome

Timeframe: 3 Weeks

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. Missing data were not imputed. Only subjects who recorded sufficient pain scores in each treatment period were included in this analysis.

Outcome measures

Measure	XPF-002 n=52 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=52 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Proportion of Subjects Achieving 30% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment	21 participants	12 participants

SECONDARY outcome

Timeframe: 3 Weeks

Outcome measures

Measure	XPF-002 n=57 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=57 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Proportion of Subjects Using Rescue Analgesic Medications During XPF-002 Treatment Compared to Placebo Treatment	38 participants	40 participants

SECONDARY outcome

Timeframe: 3 Weeks

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. The maximum number of subjects who could contribute to this population is 57. Last Observation Carried Forward (LOCF) was used to impute any missing data.

Subjects completed the NPSI questionaire at various timepoints during the study. An overall NPSI score (the sum of 10 quantitative responses, each scored 0-10, max score = 100) was calculated each time the NPSI questionaire was completed.

This measurement is the 'Change in Neuropathic Pain Symptom Inventory (NPSI) score from baseline between the 3rd week of XPF-002 treatment and the 3rd week of placebo treatment for each subject. If the NPSI score for Week 3 was missing, the last value from within the same treatment period was used (ie last observation carried forward (LOCF)).

The reduction in NPSI on each treatment compared to baseline is reported as a negative number. A larger negative number, indicates a greater reduction in neuropathic pain symptoms. (A positive number would indicate neuropathic pain symptoms were increased compared to baseline.)

Outcome measures

Measure	XPF-002 n=53 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=53 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Change in Overall Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 3 (With LOCF)	-6.7 units on a scale Standard Deviation 16.28	-6.1 units on a scale Standard Deviation 13.51

SECONDARY outcome

Timeframe: 3 Weeks

Population: The Efficacy Evaluable Population was used for this analysis. This population includes randomised subjects who recorded both baseline and post-baseline data in both treatment periods. The maximum number of subjects who could contribute to this population is 57. Last Observation Carried Forward (LOCF) was used to impute any missing data.

Subjects recorded their sleep interference scores each morning for the previous night's sleep (using an 11-point Likert numerical rating scale (NRS); 0-10, where 0 = no interference with sleep and 10 = pain completely interfered with sleep). A daily sleep interference score was calculated.

This measurement is the 'Change in DSIS score from baseline between the 3rd week of XPF-002 treatment and the 3rd week of placebo treatment for each subject'. Any missing scores were imputed using last observation carried forward (LOCF).

The reduction in DSIS on each treatment compared to baseline is reported as a negative number. A larger negative number, indicates a greater reduction in sleep interference due to pain. (A positive number would indicate sleep interference due to pain was increased compared to baseline.)

Outcome measures

Measure	XPF-002 n=53 Participants XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=53 Participants Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Change in Daily Sleep Interference Scale (DSIS) From Baseline to Week 3 of XPF-002 Treatment Compared to Week 3 of Placebo Treatment (With LOCF)	-0.81 units on a scale Interval -1.21 to -0.41	-0.84 units on a scale Interval -1.24 to -0.43

Adverse Events

XPF-002

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	XPF-002 n=62 participants at risk XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=63 participants at risk Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
Infections and infestations Tooth abcess	0.00% 0/62	1.6% 1/63 • Number of events 1
Cardiac disorders Coronary artery disease	1.6% 1/62 • Number of events 1	0.00% 0/63

Other adverse events

Measure	XPF-002 n=62 participants at risk XPF-002: 8% strength ointment, applied twice daily for 3 weeks in either the first intervention period or second intervention period.	Placebo n=63 participants at risk Placebo: Vehicle only ointment, applied twice daily for 3 weeks in either first intervention period or second intervention period.
General disorders Application site pain	3.2% 2/62	15.9% 10/63
General disorders Application site pruritus	3.2% 2/62	12.7% 8/63
General disorders Application site exfoliation	4.8% 3/62	7.9% 5/63
General disorders Application site rash	6.5% 4/62	4.8% 3/63
General disorders Application site erythema	6.5% 4/62	1.6% 1/63

Additional Information

Dr. Paul Goldberg, VP Clinical Development

Xenon Pharmaceuticals Inc.

Phone: 604-484-3300

Email: pgoldberg@xenon-pharma.com

Results disclosure agreements

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

Restriction type: GT60