Trial Outcomes & Findings for Phase 2a, Exploratory Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of XPF-002 in Patients With Primary/Inherited Erythromelalgia (NCT NCT01486446)

NCT ID: NCT01486446

Last Updated: 2014-04-14

Results Overview

Using diary cards, subjects recorded the use of all non-pharmacological cooling methods used to relieve their erythromelalgia (EM) pain each day during Treatment Period 2. A smaller average number of cooling uses each day in Treatment Period 2 indicates that subjects were in less pain/required less use of cooling to relieve their EM pain and vice versa.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

8 participants

Primary outcome timeframe

14-21 Days

Results posted on

2014-04-14

Participant Flow

Participant milestones

Participant milestones
Measure
XPF-002
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Overall Study
STARTED
7
1
Overall Study
COMPLETED
6
1
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
XPF-002
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Overall Study
Adverse Event
1
0

Baseline Characteristics

Phase 2a, Exploratory Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of XPF-002 in Patients With Primary/Inherited Erythromelalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Total
n=8 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=99 Participants
0 Participants
n=107 Participants
0 Participants
n=206 Participants
Age, Categorical
Between 18 and 65 years
6 Participants
n=99 Participants
0 Participants
n=107 Participants
6 Participants
n=206 Participants
Age, Categorical
>=65 years
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Age, Continuous
39.7 years
STANDARD_DEVIATION 19.3 • n=99 Participants
77 years
STANDARD_DEVIATION NA • n=107 Participants
44.4 years
STANDARD_DEVIATION 22.2 • n=206 Participants
Sex: Female, Male
Female
6 Participants
n=99 Participants
1 Participants
n=107 Participants
7 Participants
n=206 Participants
Sex: Female, Male
Male
1 Participants
n=99 Participants
0 Participants
n=107 Participants
1 Participants
n=206 Participants
Region of Enrollment
United States
7 participants
n=99 Participants
1 participants
n=107 Participants
8 participants
n=206 Participants

PRIMARY outcome

Timeframe: 14-21 Days

Using diary cards, subjects recorded the use of all non-pharmacological cooling methods used to relieve their erythromelalgia (EM) pain each day during Treatment Period 2. A smaller average number of cooling uses each day in Treatment Period 2 indicates that subjects were in less pain/required less use of cooling to relieve their EM pain and vice versa.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Average Daily Use of Cooling for Erythromelalgia-Related Pain in Treatment Period 2
0.24 cooling uses/day
Interval 0.03 to 0.27
2.4 cooling uses/day
Only 1 placebo subject, therefore no IQR.

OTHER_PRE_SPECIFIED outcome

Timeframe: 14-21 Days

Using diary cards, subjects recorded the use and duration of all non-pharmacological cooling methods used to relieve their EM pain each day during Treatment Period 2. A smaller average duration of cooling each day in Treatment Period 2 indicates that subjects were in less pain/required less use of cooling to relieve their EM pain and vice versa.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Average Cooling Duration (Minutes Per Day) for EM-related Pain in Treatment Period 2
7.8 minutes/day
Interval 0.0 to 13.3
86 minutes/day
Only 1 placebo subject, therefore no IQR.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 5

A standard heat induction was performed on multiple occasions pre-and post treatment. Subjects placed their feet in front of an electric heater for up to 75 minutes. Subjects rated their pain intensity/severity using numerical and categorical rating scales at fixed intervals before, during and after the heating procedure. The heating procedure continued until one of the pre-defined stopping criteria were met, or when the 75 minutes were over. Subjects could stop the procedure at any time if pain was intolerable. A stopwatch was used to record the time the heating procedure was stopped. This time is known as "Time to Exit". A longer Time to Exit compared to Baseline indicates that subjects were able to tolerate the heat for a longer period when on treatment.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 1, Compared to Baseline
138 Percentage of Baseline
Interval 78.0 to 188.0
96 Percentage of Baseline
Only 1 placebo subject, therefore no IQR.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 14 or 21 days

A standard heat induction was performed on multiple occasions pre-and post treatment. Subjects placed their feet in front of an electric heater for up to 75 minutes. Subjects rated their pain intensity/severity using numerical and categorical rating scales at fixed intervals before, during and after the heating procedure. The heating procedure continued until one of the pre-defined stopping criteria were met, or when the 75 minutes were over. Subjects could stop the procedure at any time if pain was intolerable. A stopwatch was used to record the time the heating procedure was stopped. This time is known as "Time to Exit". A longer Time to Exit compared to Baseline indicates that subjects were able to tolerate the heat for a longer period when on treatment.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 2, Compared to Baseline
100 Percentage of Baseline
Interval 92.0 to 112.0
107 Percentage of Baseline
Only 1 placebo subject, therefore no IQR.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 5

A standard heat induction was performed on multiple occasions pre-and post treatment. Subjects placed their feet in front of an electric heater for up to 75 minutes. Subjects rated their pain intensity/severity using numerical and categorical rating scales at fixed intervals before, during and after the heating procedure. The heating procedure continued until one of the pre-defined stopping criteria were met, or when the 75 minutes were over. Subjects could stop the procedure at any time if pain was intolerable. A stopwatch was used to record the time the subject recorded a pain intensity numerical score of 5 or more (on a scale of 0-10). This time is known as "Time to Moderate Pain". A longer Time to Moderate Pain compared to Baseline indicates that subjects were able to tolerate the heat for a longer period when on treatment.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 1, Compared to Baseline
137 Percentage of Baseline
Interval 74.0 to 172.0
90 Percentage of Baseline
Only 1 placebo subject, therefore no IQR.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 14 or 21 days

A standard heat induction was performed on multiple occasions pre-and post treatment. Subjects placed their feet in front of an electric heater for up to 75 minutes. Subjects rated their pain intensity/severity using numerical and categorical rating scales at fixed intervals before, during and after the heating procedure. The heating procedure continued until one of the pre-defined stopping criteria were met, or when the 75 minutes were over. Subjects could stop the procedure at any time if pain was intolerable. A stopwatch was used to record the time the subject recorded a pain intensity numerical score of 5 or more (on a scale of 0-10). This time is known as "Time to Moderate Pain". A longer Time to Moderate Pain compared to Baseline indicates that subjects were able to tolerate the heat for a longer period when on treatment.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 2, Compared to Baseline
103 Percentage of Baseline
Interval 91.0 to 115.0
135 Percentage of Baseline
Only 1 placebo subject, therefore no IQR.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 14 or 21 days

During Baseline and Treatment Period 2, subjects recorded pain scores in their diary cards 3 times each day (upon waking, lunchtime and evening). On each recording occasion, subjects recorded the maximum pain experienced since the previous recording occasion using an 11 point numerical rating scale of pain intensity, PINRS (where 0 = no pain and 10 = worst pain imaginable). A lower score compared to Baseline indicates that the subjects experienced less severe pain on treatment than during Baseline.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Daily Pain (Maximum Pain Intensity) in Treatment Period 2, Compared to Baseline
78.5 Percentage of Baseline
Interval 75.9 to 94.2
76 Percentage of Baseline
Only 1 placebo subject, therefore there is no IQR.

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 14 or 21 days

During Baseline and Treatment Period 2, subjects recorded sleep interference scores in their diary cards for each night (scores were recorded upon waking). Sleep Interference due to pain is scored using an 11 point numerical rating scale where 0 = pain does not interfere with sleep and 10 = completely interferes, unable to sleep due to pain. A lower sleep interference score compared to Baseline indicates that the subjects' pain interfered with sleep less on treatment than during Baseline.

Outcome measures

Outcome measures
Measure
XPF-002
n=7 Participants
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 Participants
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Sleep Interference Due to Pain in Treatment Period 2, Compared to Baseline
76.5 Percentage of Baseline
Interval 48.8 to 86.9
46 Percentage of Baseline
Only 1 placebo subject, therefore no IQR.

Adverse Events

XPF-002

Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
XPF-002
n=7 participants at risk
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 participants at risk
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Vascular disorders
Hospitalization due to worsening erythromelalgia pain
14.3%
1/7 • Number of events 1
0.00%
0/1

Other adverse events

Other adverse events
Measure
XPF-002
n=7 participants at risk
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
Placebo
n=1 participants at risk
XEN402 0% w/w ointment for topical application. Identical content and appearance to the XPF-002 ointment but without the active medicine. Applied to the skin twice daily for 14 or 21 days.
Nervous system disorders
Headache
42.9%
3/7 • Number of events 8
0.00%
0/1
Nervous system disorders
Paraesthesia
28.6%
2/7 • Number of events 3
0.00%
0/1
Nervous system disorders
Burning sensation
14.3%
1/7 • Number of events 1
0.00%
0/1
Nervous system disorders
Sinus headache
14.3%
1/7 • Number of events 1
0.00%
0/1
General disorders
Nodule
14.3%
1/7 • Number of events 4
0.00%
0/1
General disorders
Flushing
14.3%
1/7 • Number of events 1
0.00%
0/1
General disorders
Malaise
14.3%
1/7 • Number of events 1
0.00%
0/1
General disorders
Pain
0.00%
0/7
100.0%
1/1 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
42.9%
3/7 • Number of events 3
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
14.3%
1/7 • Number of events 2
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Cough
14.3%
1/7 • Number of events 1
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
14.3%
1/7 • Number of events 1
0.00%
0/1
Skin and subcutaneous tissue disorders
Rash
28.6%
2/7 • Number of events 3
0.00%
0/1
Skin and subcutaneous tissue disorders
Erythema
14.3%
1/7 • Number of events 2
0.00%
0/1
Skin and subcutaneous tissue disorders
Rash pruritic
14.3%
1/7 • Number of events 1
0.00%
0/1
Skin and subcutaneous tissue disorders
Skin exfoliation
0.00%
0/7
100.0%
1/1 • Number of events 1
Gastrointestinal disorders
Nausea
28.6%
2/7 • Number of events 2
0.00%
0/1
Gastrointestinal disorders
Oopharyngeal pain
14.3%
1/7 • Number of events 2
0.00%
0/1
Gastrointestinal disorders
Tooth infection
14.3%
1/7 • Number of events 1
0.00%
0/1
Vascular disorders
Flushing
14.3%
1/7 • Number of events 3
0.00%
0/1
Vascular disorders
Cyanosis
14.3%
1/7 • Number of events 1
0.00%
0/1
Ear and labyrinth disorders
External ear inflammation
14.3%
1/7 • Number of events 2
0.00%
0/1
Musculoskeletal and connective tissue disorders
Arthralgia
14.3%
1/7 • Number of events 1
0.00%
0/1
Musculoskeletal and connective tissue disorders
Muscle spasms
14.3%
1/7 • Number of events 1
0.00%
0/1
Eye disorders
Eye inflammation
14.3%
1/7 • Number of events 1
0.00%
0/1
Renal and urinary disorders
Urinary tract infection
14.3%
1/7 • Number of events 1
0.00%
0/1

Additional Information

Dr. Y Paul Goldberg

Xenon Pharmaceuticals Inc.

Phone: 604 484 3300

Results disclosure agreements

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

Restriction type: GT60