Inherited Erythromelalgia, Primary Erythromelalgia
Conditions
Keywords
IEM, EM, Erythromelalgia, Erythermalgia, Red neuralgia, Peripheral Vascular Disease, Vascular Disease, Cardiovascular Disease
Brief summary
This is a Phase 2a single-center, randomized, double-blind, Placebo-controlled, parallel group study with XPF-002 applied twice daily over 14 or 21 days in patients with Primary/Inherited Erythromelalgia (IEM). The purpose of this study is to determine whether XPF-002 is safe and effective in the treatment of pain caused by IEM.
Detailed description
Your role in the study would include: * Travelling to the clinic (in Anniston, Alabama, USA) for 3 out-patient visits, each lasting approximately 1 day * Travelling and staying in the clinic for 2 in-patient stays: * For the first in-patient visit you will have to spend 8 days and 7 nights in the clinic * For the second in-patient visit you will have to spend 2 days and 1 night in the clinic You can bring books, laptops and DVDs to the clinic. If you do not live within driving distance to the clinic you will need to stay in the local area (in Anniston, at a local hotel) for 1 to 2 weeks while you use the ointment, in addition to the in-patient portion of the study.
Interventions
DRUGXPF-002
XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days
DRUGPlacebo
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.
Sponsors
Xenon Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Must have a Body Mass Index (BMI) of 18-40 kg/m2 (inclusive) * Have primary or inherited erythromelalgia (IEM) * Experience flares of pain in your feet or hands caused by erythromelalgia * Be generally healthy (apart from your pain) * Stop taking your usual pain medications and certain other medications for up to 11.5 weeks * Not be pregnant or breast-feeding * Must be able and willing to provide informed consent and willing to comply with all study procedures and restrictions
Exclusion criteria
* Must not be in constant pain (must not continually be in moderate pain, 3/10 or more) * Coexistent source of pain from other conditions that may interfere with the study interpretation * HIV, Hepatitis B or C * Treatment for significant depression within 6 months of Screening * Not willing to use adequate contraception * Alcoholism, alcohol or substance abuse * Presence or history of major psychiatric disturbance * Any other condition or finding that may pose undue risk for participation * Use of any other investigational drug in the 30 days prior to dosing * Donation or loss of whole blood or plasma prior to dosing as follows: 50 mL to 499 mL within 30 days, or more than 499 mL within 56 days * Employee or relative of an employee who is directly involved in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Use of Cooling for Erythromelalgia-Related Pain in Treatment Period 2 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 1, Compared to Baseline | 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. |
| Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 2, Compared to Baseline | 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. |
| Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 1, Compared to Baseline | 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. |
| Average Cooling Duration (Minutes Per Day) for EM-related Pain in Treatment Period 2 | 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. |
| Daily Pain (Maximum Pain Intensity) in Treatment Period 2, Compared to Baseline | 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. |
| Sleep Interference Due to Pain in Treatment Period 2, Compared to Baseline | 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. |
| Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 2, Compared to Baseline | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| XPF-002 XEN402 8% w/w ointment for topical application, applied to the skin twice daily for 14 or 21 days | 7 |
| 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. | 1 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | XPF-002 | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 0 Participants |
| Age, Continuous | 39.7 years STANDARD_DEVIATION 19.3 | 44.4 years STANDARD_DEVIATION 22.2 | 77 years |
| Region of Enrollment United States | 7 participants | 8 participants | 1 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 1 / 1 |
| serious Total, serious adverse events | 1 / 7 | 0 / 1 |
Outcome results
Primary
Average Daily Use of Cooling for Erythromelalgia-Related Pain in Treatment Period 2
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Average Daily Use of Cooling for Erythromelalgia-Related Pain in Treatment Period 2 | 0.24 cooling uses/day |
| Placebo | Average Daily Use of Cooling for Erythromelalgia-Related Pain in Treatment Period 2 | 2.4 cooling uses/day |
Other Pre-specified
Average Cooling Duration (Minutes Per Day) for EM-related Pain in Treatment Period 2
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Average Cooling Duration (Minutes Per Day) for EM-related Pain in Treatment Period 2 | 7.8 minutes/day |
| Placebo | Average Cooling Duration (Minutes Per Day) for EM-related Pain in Treatment Period 2 | 86 minutes/day |
Other Pre-specified
Daily Pain (Maximum Pain Intensity) in Treatment Period 2, Compared to Baseline
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Daily Pain (Maximum Pain Intensity) in Treatment Period 2, Compared to Baseline | 78.5 Percentage of Baseline |
| Placebo | Daily Pain (Maximum Pain Intensity) in Treatment Period 2, Compared to Baseline | 76 Percentage of Baseline |
Other Pre-specified
Sleep Interference Due to Pain in Treatment Period 2, Compared to Baseline
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Sleep Interference Due to Pain in Treatment Period 2, Compared to Baseline | 76.5 Percentage of Baseline |
| Placebo | Sleep Interference Due to Pain in Treatment Period 2, Compared to Baseline | 46 Percentage of Baseline |
Other Pre-specified
Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 1, Compared to Baseline
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 1, Compared to Baseline | 138 Percentage of Baseline |
| Placebo | Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 1, Compared to Baseline | 96 Percentage of Baseline |
Other Pre-specified
Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 2, Compared to Baseline
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 2, Compared to Baseline | 100 Percentage of Baseline |
| Placebo | Time to Exit (Minutes) From Standard Heat Inductions in Treatment Period 2, Compared to Baseline | 107 Percentage of Baseline |
Other Pre-specified
Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 1, Compared to Baseline
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 1, Compared to Baseline | 137 Percentage of Baseline |
| Placebo | Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 1, Compared to Baseline | 90 Percentage of Baseline |
Other Pre-specified
Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 2, Compared to Baseline
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| XPF-002 | Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 2, Compared to Baseline | 103 Percentage of Baseline |
| Placebo | Time to Moderate Pain (Minutes) During Standard Heat Inductions in Treatment Period 2, Compared to Baseline | 135 Percentage of Baseline |