Diabetic Neuropathy, Idiopathic Distal Sensory Polyneuropathy, Neuralgia, Postherpetic, Painful Small-Fiber Neuropathy
Conditions
Brief summary
The purpose of this study is to determine the best way to conduct clinical trials in patients with neuropathic pain (nerve pain). This study will see if generic pregabalin has any effect on neuropathic pain.
Interventions
DRUGComparator: pregabalin
pregabalin (up to 600 mg/day by mouth (po)). Duration of Treatment: 6 Weeks
DRUGComparator: Placebo (unspecified)
pregabalin Pbo (up to 600 mg/day by mouth (po)). Duration of Treatment: 6 Weeks
Sponsors
Merck Sharp & Dohme LLC
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
* Patient has moderate to severe nerve pain due to one of the following conditions: Postherpetic neuralgia, Painful diabetic neuropathy, Small fiber neuropathy or idiopathic distal sensory polyneuropathy * Patient is able to complete questionnaires in either English or Spanish * Patient is at least 18 years of age
Exclusion criteria
* Patient is either pregnant or breastfeeding * Patient has a history of angioedema (swelling beneath the skin surface) or peripheral edema (foot, leg, and/or ankle swelling) * Patient has a history of congestive heart failure * Patient has a seizure disorder * Patient has a history of drug and/or alcohol abuse within the past 1 year * Patient failed treatment due to lack of pain relief with more than three drugs for nerve pain * Patient has had cancer (except basal cell carcinoma) within the past two years * Patient anticipates the need for surgery while participating in the study * Patient has a reported history of hepatitis B, C, or HIV infection * Patient has another type of pain that is more painful than the nerve pain * Patient has generalized anxiety disorder, untreated depression, psychosis, or post-traumatic stress disorder * Patient is involved in litigation or receives worker's compensation related to nerve pain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Evening Patient Reported Pain Intensity Scores | Baseline and 6 Weeks | Change from mean of last 3 days of maintenance period to last 3 days of double-blind period; Pain Intensity was rated on a 0-10 numeric rating scale (NRS: 0=no pain, 10=worst pain you can imagine) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 'Time to Efficacy Failure' During the Randomized Withdrawal Portion of the Study | 6 Weeks | Time to treatment failure (3 day mean of average 24 hour pain intensity ≥ 4 with at least a 30% increase relative to the last 3 days prior to randomization) |
Participant flow
Recruitment details
Last Patient Entered: 06-Dec-07 Last Patient Last Visit: 11-Sep-08 \# Sites: 20 sites randomized at least 1 patient. 21 sites screened at least 1 patient
Pre-assignment details
All patients were titrated up to the maximum tolerated dose of active treatment (pregabalin) over approximately 12 days. Patient were treated at the maximum tolerated dose until randomization at which time patient were either continued on active treatment or withdrawn from active treatment (i.e. placebo) in a double-blind fashion.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Patients who were randomized to pregabalin and were categorized in the primary responder population. Primary responders were defined as having ≥30% decrease in mean of average daily pain intensity during the last 3 days of the pre-randomization maintenance phase relative to baseline. | 30 |
| Placebo Patients who were randomized to placebo and were categorized in the primary responder population. Primary responders were defined as having ≥30% decrease in mean of average daily pain intensity during the last 3 days of the pre-randomization maintenance phase relative to baseline. | 32 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lack of Efficacy | 1 | 4 |
Baseline characteristics
| Characteristic | Pregabalin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 10.8 | 59.3 years STANDARD_DEVIATION 11 | 60.5 years STANDARD_DEVIATION 10.9 |
| Body Mass Index | 32.6 kilograms/meter^2 | 31.3 kilograms/meter^2 | 31.9 kilograms/meter^2 |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 22 Participants |
| Sex: Female, Male Male | 22 Participants | 18 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 51 | 36 / 53 |
| serious Total, serious adverse events | 0 / 51 | 1 / 53 |
Outcome results
Primary
Daily Evening Patient Reported Pain Intensity Scores
Change from mean of last 3 days of maintenance period to last 3 days of double-blind period; Pain Intensity was rated on a 0-10 numeric rating scale (NRS: 0=no pain, 10=worst pain you can imagine)
Time frame: Baseline and 6 Weeks
Population: Patients who had a ≥30% decrease in mean of average daily pain intensity during the last 3 days of the maintenance phase relative to baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin | Daily Evening Patient Reported Pain Intensity Scores | 0.14 Units on a Scale |
| Placebo | Daily Evening Patient Reported Pain Intensity Scores | 1.57 Units on a Scale |
p-value: 0.00390% CI: [-2.25, -0.6]ANOVA
Secondary
'Time to Efficacy Failure' During the Randomized Withdrawal Portion of the Study
Time to treatment failure (3 day mean of average 24 hour pain intensity ≥ 4 with at least a 30% increase relative to the last 3 days prior to randomization)
Time frame: 6 Weeks
Population: Primary Responders: ≥30% decrease in mean of average daily pain intensity during the last 3 days of the maintenance phase relative to baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pregabalin | 'Time to Efficacy Failure' During the Randomized Withdrawal Portion of the Study | 15.54 Days |
| Placebo | 'Time to Efficacy Failure' During the Randomized Withdrawal Portion of the Study | 7.87 Days |
p-value: <0.00195% CI: [5.26, 10.08]ANOVA