Neuralgia,Postherpetic
Conditions
Keywords
Postherpetic Neuralgia (PHN), shingles
Brief summary
Gabapentin and pregabalin are treatments for some types of neuropathic pain, including postherpetic neuralgia (PHN). However, these treatments usually need to be taken 3 times a day for effective pain control. The purpose of this study is to determine whether a new gabapentin tablet, which only needs to be taken once a day, is safe and effective for the treatment of postherpetic neuralgia.
Detailed description
The primary study objective is to assess the relative efficacy of G-ER dosed once daily (1800 mg following the evening meal), versus placebo in reducing the mean daily pain score from the baseline week to the end of the efficacy treatment period (Treatment Week 10) in patients with PHN. Secondary efficacy measures will include changes from baseline in mean weekly sleep interference scores, Short-Form McGill Pain Questionnaire (SF-MPQ), the Neuropathic Pain Scale (NPS), Brief Pain Inventory (BPI), Patient Global Impression of Change (PGIC), and Investigator-Rated Clinical Global Impression of Change (CGIC).
Interventions
Once-Daily; 300 mg and 600 mg tablets
DRUGPlacebo
Once daily; 300 mg and 600 mg tablets
Sponsors
Depomed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men or women 18 years or older who have experienced pain for at least 6 months, but not more than 5 years after the healing of a herpes zoster skin rash(typically about 4 months after the rash first appears). 2. Patient has a pain intensity score of at least 4 on the 11-point Numerical Rating Scale (NRS). Patients should never be informed of the pain intensity criterion prior to screening or randomization. 3. Patients of child-bearing potential must have a negative serum pregnancy test at screening and a negative follow-up urine pregnancy test at randomization. 4. Patient has a mean baseline week pain intensity score of at least 4 on the 11-point NRS scale at the end of a 1-week baseline period and has completed at least 4 days of daily pain diary entries during the baseline week. 5. Patients must have a minimum washout period of greater than 5 times the half-life of the drug of several medications. 6. Patients currently treated with gabapentin pr pregabalin at screening may be eligible for the study, but must have a tapering period wherein the dose of gabapentin or pregabalin is reduced gradually over a period of 5 days followed by a two day washout prior to the Baseline Week.
Exclusion criteria
1. Patients who have previously not responded to treatment for PHN with gabapentin or pregabalin. 2. Patients who previously experienced dose-limiting adverse effects that prevented titration of gabapentin to an effective dose. 3. Patient is a nursing mother. 4. Patient has hypersensitivity to gabapentin. 5. Patient has had neurolytic or neurosurgical treatment for PHN. 6. Patient has severe pain from causes other than PHN. 7. Patient has used injected anesthetics or steroids within 30 days of baseline. 8. Patient has skin conditions in the area affected by the neuropathy that could alter sensation. 9. Patient is in an immunocompromised state. 10. Patient has an estimated creatinine clearance less than 50 ml/min. 11. Patient has had malignancy within past 2 years other than basal cell carcinoma. 12. Patient has had gastric reduction surgery. 13. Patient has severe chronic diarrhea, chronic constipation \[unless attributed to drugs that will be washed out\], uncontrolled irritable bowel syndrome (IBS) or unexplained weight loss. 14. Patient has any abnormal chemistry or hematology results that are deemed by the investigator to be clinically significant. 15. Patient has a history of substance abuse within the past year. 16. Patient has a history of seizure (except for infantile febrile seizure) or is at risk of seizure due to head trauma. 17. Patient has a history of chronic hepatitis B or C, hepatitis within the past 3 months, or HIV infection. 18. Patient has any other clinically significant medical or psychological condition that, in the opinion of the Investigator would jeopardize the safety of the patient or affect the validity of the study results. 19. Continuing use of any concomitant medication excluded by Inclusion Criterion 5. 20. Patient has participated in a clinical trial of an investigational drug or device within 30 days of the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Baseline Observation Carried Forward (BOCF) Average Daily Pain Score | 10 weeks | Average daily pain scored on 11-point numerical rating scale (where 0 = no pain, 10 = worst possible pain). Results presented as least squares (LS) mean change in baseline observation carried forward (BOCF) average daily pain score from baseline to the final week of efficacy treatment period (Week 10). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change (PGIC) | 10 weeks | Patient self-assessment of how much pain had changed at end of treatment period (Week 10) compared to pain at baseline; scored on 7-point numerical rating scale (where 1 = very much improved, 7 = very much worse). Results presented as number of participants categorized at end of treatment (Week 10) as very much improved (score = 1) or much improved (score = 2). |
| Clinical Global Impression of Change (CGIC) | 10 weeks | Investigator assessment of patient's overall PHN symptoms at end of treatment period (Week 10) compared to overall PHN symptoms at baseline; scored on 7-point numerical rating scale (where 1 = very much improved, 7 = very much worse). Results presented as number of participants categorized at end of treatment (Week 10) as very much improved (score = 1) or much improved (score = 2). |
| Average Daily Sleep Interference Score | 10 weeks | Assessed on 11-point numeric rating scale (where 0 = pain does not interfere with sleep, 10 = pain completely interferes with sleep); evaluated from daily sleep entry in electronic diary. Results presented as least squares (LS) mean change in baseline observation carried forward (BOCF) average daily sleep interference score from baseline to final week of treatment period (Week 10). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Last Observation Carried Forward (LOCF) Average Daily Pain Score | 10 weeks | Average daily pain scored on 11-point numerical rating scale (where 0 = no pain, 10 = worst possible pain). Results presented as least squares (LS) mean change in last observation carried forward (LOCF) average daily pain score from baseline to final week of efficacy treatment period (Week 10). |
Countries
Argentina, Russia, United States
Participant flow
Recruitment details
Recruitment period was from March 2008 through May 2009.
Pre-assignment details
Study included screening visit, wash-out from all PHN medications as necessary, followed by a week of baseline period. Patients who successfully completed the baseline week, if still continues to meet entry criteria, then get randomized to Active or Placebo groups.
Participants by arm
| Arm | Count |
|---|---|
| G-ER Gabapentin Extended Release 1800 mg once daily (qd); 300 mg and 600 mg tablets, oral dosing | 220 |
| Placebo Placebo 1800 mg once daily (qd); 300 mg and 600 mg sugar pills, oral dosing | 230 |
| Total | 450 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 19 | 8 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 7 | 12 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other reason | 4 | 6 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 9 |
Baseline characteristics
| Characteristic | G-ER | Placebo | Total |
|---|---|---|---|
| Age Continuous | 65.3 years STANDARD_DEVIATION 13.3 | 65.9 years STANDARD_DEVIATION 11.1 | 65.6 years STANDARD_DEVIATION 12.2 |
| Age, Customized 65 to 74 years | 82 participants | 86 participants | 168 participants |
| Age, Customized <65 years | 81 participants | 89 participants | 170 participants |
| Age, Customized >=75 years | 57 participants | 55 participants | 112 participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 10 Participants | 6 Participants | 16 Participants |
| Race/Ethnicity, Customized Caucasian | 196 Participants | 204 Participants | 400 Participants |
| Race/Ethnicity, Customized Other | 13 Participants | 18 Participants | 31 Participants |
| Sex: Female, Male Female | 134 Participants | 147 Participants | 281 Participants |
| Sex: Female, Male Male | 86 Participants | 83 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 92 / 221 | 63 / 231 |
| serious Total, serious adverse events | 4 / 221 | 6 / 231 |
Outcome results
Primary
Mean Change in Baseline Observation Carried Forward (BOCF) Average Daily Pain Score
Average daily pain scored on 11-point numerical rating scale (where 0 = no pain, 10 = worst possible pain). Results presented as least squares (LS) mean change in baseline observation carried forward (BOCF) average daily pain score from baseline to the final week of efficacy treatment period (Week 10).
Time frame: 10 weeks
Population: ITT, BOCF
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| G-ER | Mean Change in Baseline Observation Carried Forward (BOCF) Average Daily Pain Score | -2.12 Scores on a scale | 95% Confidence Interval 0.17 |
| Placebo | Mean Change in Baseline Observation Carried Forward (BOCF) Average Daily Pain Score | -1.63 Scores on a scale | 95% Confidence Interval 0.16 |
p-value: 0.012595% CI: [-0.88, -0.11]ANCOVA
Secondary
Average Daily Sleep Interference Score
Assessed on 11-point numeric rating scale (where 0 = pain does not interfere with sleep, 10 = pain completely interferes with sleep); evaluated from daily sleep entry in electronic diary. Results presented as least squares (LS) mean change in baseline observation carried forward (BOCF) average daily sleep interference score from baseline to final week of treatment period (Week 10).
Time frame: 10 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| G-ER | Average Daily Sleep Interference Score | -2.30 Scores on a scale | Standard Error 0.16 |
| Placebo | Average Daily Sleep Interference Score | -1.59 Scores on a scale | Standard Error 0.15 |
p-value: 0.000195% CI: [-1.07, -0.35]ANCOVA
Secondary
Clinical Global Impression of Change (CGIC)
Investigator assessment of patient's overall PHN symptoms at end of treatment period (Week 10) compared to overall PHN symptoms at baseline; scored on 7-point numerical rating scale (where 1 = very much improved, 7 = very much worse). Results presented as number of participants categorized at end of treatment (Week 10) as very much improved (score = 1) or much improved (score = 2).
Time frame: 10 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-ER | Clinical Global Impression of Change (CGIC) | 97 Participants |
| Placebo | Clinical Global Impression of Change (CGIC) | 78 Participants |
Comparison: P-value (vs Placebo) for pairwise test of treatment effect between G-ER group and Placebo group is based on Z test for difference between the 2 groups in proportion of participants who were categorized as very much or much improved in CGIC at endpoint. Proportion in each group calculated from number of participants categorized as very much or much improved relative to total number of participants in ITT population.p-value: 0.026895% CI: [0.01, 0.19]Z test
Secondary
Patient Global Impression of Change (PGIC)
Patient self-assessment of how much pain had changed at end of treatment period (Week 10) compared to pain at baseline; scored on 7-point numerical rating scale (where 1 = very much improved, 7 = very much worse). Results presented as number of participants categorized at end of treatment (Week 10) as very much improved (score = 1) or much improved (score = 2).
Time frame: 10 weeks
Population: ITT, BOCF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-ER | Patient Global Impression of Change (PGIC) | 94 Participants |
| Placebo | Patient Global Impression of Change (PGIC) | 77 Participants |
Comparison: P-value (vs Placebo) for pairwise test of treatment effect between G-ER group and Placebo group is based on Z test for difference between the 2 groups in proportion of participants who were categorized as very much or much improved in PGIC at endpoint. Proportion in each group calculated from number of participants categorized as very much or much improved relative to total number of participants in ITT population.p-value: 0.043495% CI: [0, 0.18]Z test
Other Pre-specified
Mean Change in Last Observation Carried Forward (LOCF) Average Daily Pain Score
Average daily pain scored on 11-point numerical rating scale (where 0 = no pain, 10 = worst possible pain). Results presented as least squares (LS) mean change in last observation carried forward (LOCF) average daily pain score from baseline to final week of efficacy treatment period (Week 10).
Time frame: 10 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| G-ER | Mean Change in Last Observation Carried Forward (LOCF) Average Daily Pain Score | -2.40 Scores on a scale | Standard Error 0.17 |
| Placebo | Mean Change in Last Observation Carried Forward (LOCF) Average Daily Pain Score | -1.85 Scores on a scale | Standard Error 0.17 |
p-value: 0.00795% CI: [-0.96, -0.15]ANCOVA