Postherpetic Neuralgia
Conditions
Keywords
Pain from Shingles, PHN, Postherpetic Neuralgia
Brief summary
The purpose of this trial is to determine if XPF-002 is safe and effective for the treatment of pain in subjects with Postherpetic Neuralgia
Interventions
DRUGXPF-002
Twice daily application of XPF-002 ointment which contains 8% of the XPF-002 active ingredient
DRUGPlacebo
Twice daily application of Placebo ointment
Sponsors
Xenon Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years (inclusive); * Males or females of non-childbearing potential (ie, 12 months or more of spontaneous amenorrhea, bilateral oophorectomy at least 6 months prior to randomization, hysterectomy with bilateral oophorectomy at least 6 months prior to randomization, or for females over 50 years of age, hysterectomy without bilateral oophorectomy at least 6 months prior to randomization); * Male subjects with sexual partners of childbearing potential must agree to use contraception (abstinence, birth control pills, rings or patches, diaphragm and spermicide, intrauterine device, condom and vaginal spermicide, surgical sterilization, vasectomy, progestin implant or injection); * Persistent pain for more than 6 months from the appearance of herpes zoster rash that is not located on the face, above the scalp hairline, or in proximity to mucous membranes; * Diagnosis of PHN; * Persistent neuropathic pain that involves at least 1 dermatome and covering no more than 400 cm2; * Mean daily pain intensity score in the target area of greater than or equal to 4 on an 11-point Likert NRS for a minimum of 4 days during the single-blind, placebo run-in period; * Subject agrees to take only the protocol-defined rescue medication as prescribed; * Intact skin over the painful area to be treated; and * Able and willing to provide informed consent and comply with study procedures.
Exclusion criteria
* Subject with systemic disease that would put him/her at an additional risk or limit his/her ability to participate in the study in the opinion of the investigator; * Creatinine clearance less than 30 mL/min; * Subject with known history of human immunodeficiency virus, hepatitis C, or hepatitis B; * Malignancy other than basal cell carcinoma and carcinoma in situ within the past 2 years; * Subject with history of serious mental illness or psychiatric illness such as dementia, depression, or schizophrenia, that will limit his/her ability to comply with study procedures; * Subject who is unable to apply, or have a care giver apply, study ointment to the area of most painful skin segments, BID, once within 2 hours of waking and once in the evening after dinner; * Subject with known sensitivity to topical products; * Subject with active herpes zoster lesions or dermatitis; * Other severe or chronic pain that may impair the self-assessment of the pain due to PHN; * Treatment with local anesthetic in the last 2 weeks or nerve blocks within the last 30 days; * Subject who is taking any opioid medications to treat his/her PHN pain and is unable to washout of these medications for the duration of the study; * Subject who is taking any prohibited medication and is unable to washout of these treatments for the duration of the study; * Subject who is taking more than 2 permitted concomitant medications for the treatment of PHN and is unable to washout of all but 2 of these treatments for the duration of the study; * Subject who is taking any local prescription or non-prescription therapy (lidocaine patch, transcutaneous electrical nerve stimulation, etc.) and is unable to washout of these treatments for the duration of the study; * Subject who has used Qutenza® patches in the 90 days prior to screening or has used other capsaicin preparations on a daily basis in the 90 days prior to screening; * Subject who has participated in more than 1 other topical study for pain and more than 3 other PHN clinical studies; * Pregnant or lactating females; * Subject who has an active history of alcohol or drug abuse; * Subject who has participated in any other investigational study within 60 days prior to screening; * Subject who is employed by the Sponsor, study staff, and their families; or * Subject who has any condition that would make him/her, in the opinion of the investigator or Sponsor, unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Daily Pain Score From Baseline to Week 3 (With LOCF) | 3 weeks | 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.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Daily Pain Score From Baseline to Week 2 | 2 week | 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.) |
| Change in Mean Daily Pain Score From Baseline to Week 3 | 3 Weeks | 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.) |
| 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 | 3 Weeks | 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. |
| Proportion of Subjects Achieving 50% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment | 3 weeks | — |
| Change in Mean Daily Pain Score From Baseline to Week 1 | 1 week | 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.) |
| Proportion of Subjects Using Rescue Analgesic Medications During XPF-002 Treatment Compared to Placebo Treatment | 3 Weeks | — |
| Change in Overall Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 3 (With LOCF) | 3 Weeks | 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.) |
| 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) | 3 Weeks | 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.) |
| Proportion of Subjects Achieving 30% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment | 3 Weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| XPF-002 First, Then Placebo XPF-002 ointment applied twice daily for 3 weeks followed by Placebo ointment applied twice daily for 3 weeks (after a washout period) | 35 |
| Placebo First, Then XPF-002 Placebo ointment applied twice daily for 3 weeks followed by XPF-002 ointment applied twice daily for 3 weeks (after a washout period) | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (3 Weeks) | Adverse Event | 2 | 3 |
| First Intervention (3 Weeks) | Lost to Follow-up | 1 | 0 |
| First Intervention (3 Weeks) | Protocol Violation | 1 | 0 |
| First Intervention (3 Weeks) | Withdrawal by Subject | 1 | 0 |
| Second Intervention (3 Weeks) | Adverse Event | 1 | 1 |
| Second Intervention (3 Weeks) | Withdrawal by Subject | 0 | 1 |
| Washout Period (2 Weeks) | Adverse Event | 1 | 1 |
| Washout Period (2 Weeks) | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo First, Then XPF-002 | XPF-002 First, Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 17 Participants | 11 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 23 Participants | 41 Participants |
| Age Continuous | 63.1 years STANDARD_DEVIATION 9.73 | 58.3 years STANDARD_DEVIATION 13.58 | 60.7 years STANDARD_DEVIATION 11.98 |
| Region of Enrollment United States | 35 participants | 35 participants | 70 participants |
| Sex: Female, Male Female | 19 Participants | 20 Participants | 39 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 62 | 17 / 63 |
| serious Total, serious adverse events | 1 / 62 | 1 / 63 |
Outcome results
Primary
Change in Mean Daily Pain Score From Baseline to Week 3 (With LOCF)
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.)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| XPF-002 | Change in Mean Daily Pain Score From Baseline to Week 3 (With LOCF) | -0.94 units on a scale |
| Placebo | Change in Mean Daily Pain Score From Baseline to Week 3 (With LOCF) | -0.97 units on a scale |
Secondary
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)
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.)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| XPF-002 | 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 |
| Placebo | 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) | -0.84 units on a scale |
Secondary
Change in Mean Daily Pain Score From Baseline to Week 1
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.)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| XPF-002 | Change in Mean Daily Pain Score From Baseline to Week 1 | -0.42 units on a scale |
| Placebo | Change in Mean Daily Pain Score From Baseline to Week 1 | -0.55 units on a scale |
Secondary
Change in Mean Daily Pain Score From Baseline to Week 2
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.)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| XPF-002 | Change in Mean Daily Pain Score From Baseline to Week 2 | -0.74 units on a scale |
| Placebo | Change in Mean Daily Pain Score From Baseline to Week 2 | -0.70 units on a scale |
Secondary
Change in Mean Daily Pain Score From Baseline to Week 3
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.)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| XPF-002 | Change in Mean Daily Pain Score From Baseline to Week 3 | -0.96 units on a scale |
| Placebo | Change in Mean Daily Pain Score From Baseline to Week 3 | -0.96 units on a scale |
Secondary
Change in Overall Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 3 (With LOCF)
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.)
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XPF-002 | 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 |
| Placebo | Change in Overall Neuropathic Pain Symptom Inventory (NPSI) From Baseline to Week 3 (With LOCF) | -6.1 units on a scale | Standard Deviation 13.51 |
Secondary
Proportion of Subjects Achieving 30% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XPF-002 | 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 |
| Placebo | Proportion of Subjects Achieving 30% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment | 12 participants |
Secondary
Proportion of Subjects Achieving 50% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XPF-002 | 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 |
| Placebo | Proportion of Subjects Achieving 50% Improvement in Mean Daily Pain Score From Baseline to Week 3 on XPF-002 Treatment Compared to Placebo Treatment | 6 participants |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XPF-002 | 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 |
| Placebo | 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 | 19 participants |
Secondary
Proportion of Subjects Using Rescue Analgesic Medications During XPF-002 Treatment Compared to Placebo Treatment
Time frame: 3 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XPF-002 | Proportion of Subjects Using Rescue Analgesic Medications During XPF-002 Treatment Compared to Placebo Treatment | 38 participants |
| Placebo | Proportion of Subjects Using Rescue Analgesic Medications During XPF-002 Treatment Compared to Placebo Treatment | 40 participants |