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

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ClinicalTrials.gov Identifier: NCT01486446
Recruitment Status : Completed
First Posted : December 6, 2011
Results First Posted : April 14, 2014
Last Update Posted : April 14, 2014
Sponsor:
Information provided by (Responsible Party):
Xenon Pharmaceuticals Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Primary Erythromelalgia
Inherited Erythromelalgia
Interventions Drug: XPF-002
Drug: Placebo
Enrollment 8
Recruitment Details  
Pre-assignment Details  
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days 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.
Period Title: Overall Study
Started 7 1
Completed 6 1
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Arm/Group Title XPF-002 Placebo Total
Hide Arm/Group Description XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days 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 of all reporting groups
Overall Number of Baseline Participants 7 1 8
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 1 participants 8 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
  85.7%
0
   0.0%
6
  75.0%
>=65 years
1
  14.3%
1
 100.0%
2
  25.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 1 participants 8 participants
39.7  (19.3) 77 [1]   (NA) 44.4  (22.2)
[1]
Only 1 placebo subject, therefore no SD.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 1 participants 8 participants
Female
6
  85.7%
1
 100.0%
7
  87.5%
Male
1
  14.3%
0
   0.0%
1
  12.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 7 participants 1 participants 8 participants
7 1 8
1.Primary Outcome
Title Average Daily Use of Cooling for Erythromelalgia-Related Pain in Treatment Period 2
Hide Description

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.

Time Frame 14-21 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: cooling uses/day
0.24
(0.03 to 0.27)
2.4 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore no IQR.
2.Other Pre-specified Outcome
Title Average Cooling Duration (Minutes Per Day) for EM-related Pain in Treatment Period 2
Hide Description

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.

Time Frame 14-21 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: minutes/day
7.8
(0 to 13.3)
86 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore no IQR.
3.Other Pre-specified Outcome
Title Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 1, Compared to Baseline
Hide Description

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.

Time Frame Baseline to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: Percentage of Baseline
138
(78 to 188)
96 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore no IQR.
4.Other Pre-specified Outcome
Title Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 2, Compared to Baseline
Hide Description

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.

Time Frame Baseline and 14 or 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: Percentage of Baseline
100
(92 to 112)
107 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore no IQR.
5.Other Pre-specified Outcome
Title Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 1, Compared to Baseline
Hide Description

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.

Time Frame Baseline to Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: Percentage of Baseline
137
(74 to 172)
90 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore no IQR.
6.Other Pre-specified Outcome
Title Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 2, Compared to Baseline
Hide Description

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.

Time Frame Baseline and 14 or 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: Percentage of Baseline
103
(91 to 115)
135 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore no IQR.
7.Other Pre-specified Outcome
Title Daily Pain (Maximum Pain Intensity) in Treatment Period 2, Compared to Baseline
Hide Description

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.

Time Frame Baseline to 14 or 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: Percentage of Baseline
78.5
(75.9 to 94.2)
76 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore there is no IQR.
8.Other Pre-specified Outcome
Title Sleep Interference Due to Pain in Treatment Period 2, Compared to Baseline
Hide Description

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.

Time Frame Baseline to 14 or 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description:
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
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 Number of Participants Analyzed 7 1
Mean (Inter-Quartile Range)
Unit of Measure: Percentage of Baseline
76.5
(48.8 to 86.9)
46 [1] 
(NA to NA)
[1]
Only 1 placebo subject, therefore no IQR.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title XPF-002 Placebo
Hide Arm/Group Description XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days 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.
All-Cause Mortality
XPF-002 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
XPF-002 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/7 (14.29%)      0/1 (0.00%)    
Vascular disorders     
Hospitalization due to worsening erythromelalgia pain [1]  1/7 (14.29%)  1 0/1 (0.00%)  0
[1]
Subject was admitted to hospital for treatment of worsening erythromelalgia pain 131 days following their last dose of study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
XPF-002 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/7 (100.00%)      1/1 (100.00%)    
Ear and labyrinth disorders     
External ear inflammation  1/7 (14.29%)  2 0/1 (0.00%)  0
Eye disorders     
Eye inflammation  1/7 (14.29%)  1 0/1 (0.00%)  0
Gastrointestinal disorders     
Nausea  2/7 (28.57%)  2 0/1 (0.00%)  0
Oopharyngeal pain  1/7 (14.29%)  2 0/1 (0.00%)  0
Tooth infection  1/7 (14.29%)  1 0/1 (0.00%)  0
General disorders     
Nodule  1/7 (14.29%)  4 0/1 (0.00%)  0
Flushing  1/7 (14.29%)  1 0/1 (0.00%)  0
Malaise  1/7 (14.29%)  1 0/1 (0.00%)  0
Pain  0/7 (0.00%)  0 1/1 (100.00%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1/7 (14.29%)  1 0/1 (0.00%)  0
Muscle spasms  1/7 (14.29%)  1 0/1 (0.00%)  0
Nervous system disorders     
Headache  3/7 (42.86%)  8 0/1 (0.00%)  0
Paraesthesia  2/7 (28.57%)  3 0/1 (0.00%)  0
Burning sensation  1/7 (14.29%)  1 0/1 (0.00%)  0
Sinus headache  1/7 (14.29%)  1 0/1 (0.00%)  0
Renal and urinary disorders     
Urinary tract infection  1/7 (14.29%)  1 0/1 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Nasopharyngitis  3/7 (42.86%)  3 0/1 (0.00%)  0
Upper-airway cough syndrome  1/7 (14.29%)  2 0/1 (0.00%)  0
Cough  1/7 (14.29%)  1 0/1 (0.00%)  0
Rhinorrhoea  1/7 (14.29%)  1 0/1 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  2/7 (28.57%)  3 0/1 (0.00%)  0
Erythema  1/7 (14.29%)  2 0/1 (0.00%)  0
Rash pruritic  1/7 (14.29%)  1 0/1 (0.00%)  0
Skin exfoliation  0/7 (0.00%)  0 1/1 (100.00%)  1
Vascular disorders     
Flushing  1/7 (14.29%)  3 0/1 (0.00%)  0
Cyanosis  1/7 (14.29%)  1 0/1 (0.00%)  0
1
Term from vocabulary, MedDRA 15.0

This was a small trial with many exploratory efficacy measures. There was no primary outcome measure, all measures are "other: pre-specified".

Only 8 subjects were enrolled (1 placebo), the actual number of Adverse Events is used, not incidence.

Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Y Paul Goldberg
Organization: Xenon Pharmaceuticals Inc.
Phone: 604 484 3300
Responsible Party: Xenon Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT01486446     History of Changes
Other Study ID Numbers: XPF-002-202
First Submitted: December 2, 2011
First Posted: December 6, 2011
Results First Submitted: January 21, 2014
Results First Posted: April 14, 2014
Last Update Posted: April 14, 2014