Chronic Intractable Pain
Conditions
Brief summary
The purpose of this study is to determine the safety and minimum effective dose of intraspinal gabapentin when delivered through an implanted drug infusion system.
Interventions
DRUGIntraspinal Gabapentin
Surgical implantation of a drug infusion system with intrathecal (spinal) delivery of active drug (1 of 3 possible dose levels) or placebo (saline) for 22 days followed by 7 days of infusion at half dose level. Subjects may then continue in open-label treatment with study drug. Dosage in open-label may be adjusted to meet subject needs.
Sponsors
MedtronicNeuro
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chronic pain below the neck present for a minimum of one year. * Diagnosis of at least one of the following: * back pain with or without leg pain, * post-herpetic neuralgia, * complex regional pain syndrome (CRPS) 1 or 2, * diabetic neuropathy, * or a general neuropathic condition; medically stable and able to undergo surgery for implantation of the drug infusion system.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in a Pain Rating Scale After 3 Weeks of Blinded Treatment. | Baseline and Post-randomization Day 22 | Average pain score calculated over last 7 days of baseline minus average pain score calculated over last 7 days of follow-up using the Numeric Pain Rating Scale where 0=no pain, 10=worst possible pain. |
| Number of Participants With Treatment-emergent Adverse Events | Randomization to Post-randomization Day 29 (includes dose reduction) | Evaluation of adverse event profiles between placebo and active treatment groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder Analysis Between Active Treatment and Placebo Groups. | Baseline to Post-randomization Day 22 | Responders were subjects that reported at least a 30% decrease in average daily pain scores between baseline and Day 22. |
Countries
United States
Participant flow
Recruitment details
A total of 254 subjects were enrolled into the study between December 2006 and October 2009.
Pre-assignment details
During a 2-week screening period subjects were required to meet eligibility criteria including maintaining stable pain medications and demonstrating a numerical pain rating score of 6 or greater averaged over the last 7 days of screening. A total of 170 subjects met eligibility criteria, were implanted with an infusion system and were randomized.
Participants by arm
| Arm | Count |
|---|---|
| 1 Placebo Intraspinal Placebo delivered continuously for 29 days via an implantable infusion system | 44 |
| 2 Gabapentin Low Intraspinal Gabapentin Low delivered continuously for 22 days via an implantable infusion system followed by 7 days of infusion at half dose | 42 |
| 3 Gabapentin Medium Intraspinal Gabapentin Medium delivered continuously for 22 days via an implantable infusion system followed by 7 days of infusion at half dose | 41 |
| 4 Gabapentin High Intraspinal Gabapentin High delivered continuously for 22 days via an implantable infusion system followed by 7 days of infusion at half dose | 43 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawn by Sponsor | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 2 Gabapentin Low | 3 Gabapentin Medium | 1 Placebo | 4 Gabapentin High | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 5 Participants | 3 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 40 Participants | 39 Participants | 40 Participants | 160 Participants |
| Age Continuous | 50.1 years STANDARD_DEVIATION 9.9 | 48.1 years STANDARD_DEVIATION 9.4 | 51.8 years STANDARD_DEVIATION 11.2 | 48.3 years STANDARD_DEVIATION 11.1 | 49.6 years STANDARD_DEVIATION 10.5 |
| Region of Enrollment United States | 42 participants | 41 participants | 44 participants | 43 participants | 170 participants |
| Sex: Female, Male Female | 28 Participants | 20 Participants | 27 Participants | 23 Participants | 98 Participants |
| Sex: Female, Male Male | 14 Participants | 21 Participants | 17 Participants | 20 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 44 | 21 / 42 | 27 / 41 | 25 / 43 |
| serious Total, serious adverse events | 1 / 44 | 1 / 42 | 4 / 41 | 4 / 43 |
Outcome results
Primary
Changes in a Pain Rating Scale After 3 Weeks of Blinded Treatment.
Average pain score calculated over last 7 days of baseline minus average pain score calculated over last 7 days of follow-up using the Numeric Pain Rating Scale where 0=no pain, 10=worst possible pain.
Time frame: Baseline and Post-randomization Day 22
Population: Primary efficacy analysis was performed on the 167 randomized subjects that completed at least 4 days of the electronic pain diary during the last 7 days prior to the Day 22 or Early Termination Visit as per protocol. No imputation methods were used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 Placebo | Changes in a Pain Rating Scale After 3 Weeks of Blinded Treatment. | 0.48 Scores on a scale | Standard Deviation 1.52 |
| 2 Gabapentin Low | Changes in a Pain Rating Scale After 3 Weeks of Blinded Treatment. | 0.40 Scores on a scale | Standard Deviation 1.33 |
| 3 Gabapentin Medium | Changes in a Pain Rating Scale After 3 Weeks of Blinded Treatment. | 0.10 Scores on a scale | Standard Deviation 0.99 |
| 4 Gabapentin High | Changes in a Pain Rating Scale After 3 Weeks of Blinded Treatment. | -0.02 Scores on a scale | Standard Deviation 1.11 |
Comparison: Williams' test for Minimum Effective Dose was used to compare each active group to the placebo.p-value: 0.802Williams test for minimum effective dose
Comparison: Williams' test for Minimum Effective Dose was used to compare each active group to the placebo.p-value: 0.874Williams test for minimum effective dose
Comparison: Williams' test for Minimum Effective Dose was used to compare each active group to the placebo.p-value: 0.899Williams test for minimum effective dose
Primary
Number of Participants With Treatment-emergent Adverse Events
Evaluation of adverse event profiles between placebo and active treatment groups.
Time frame: Randomization to Post-randomization Day 29 (includes dose reduction)
Population: All randomized subjects were included as per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Placebo | Number of Participants With Treatment-emergent Adverse Events | 40 Participants |
| 2 Gabapentin Low | Number of Participants With Treatment-emergent Adverse Events | 32 Participants |
| 3 Gabapentin Medium | Number of Participants With Treatment-emergent Adverse Events | 37 Participants |
| 4 Gabapentin High | Number of Participants With Treatment-emergent Adverse Events | 36 Participants |
p-value: 0.083Fisher Exact
p-value: 1Fisher Exact
p-value: 0.352Fisher Exact
Secondary
Responder Analysis Between Active Treatment and Placebo Groups.
Responders were subjects that reported at least a 30% decrease in average daily pain scores between baseline and Day 22.
Time frame: Baseline to Post-randomization Day 22
Population: All 170 randomized subjects were included as per protocol. Subjects experiencing an intolerable adverse event, discontinuing due to an adverse event or lack of efficacy, or not providing data were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Placebo | Responder Analysis Between Active Treatment and Placebo Groups. | 4 Participants |
| 2 Gabapentin Low | Responder Analysis Between Active Treatment and Placebo Groups. | 4 Participants |
| 3 Gabapentin Medium | Responder Analysis Between Active Treatment and Placebo Groups. | 1 Participants |
| 4 Gabapentin High | Responder Analysis Between Active Treatment and Placebo Groups. | 2 Participants |
p-value: 1Fisher Exact
p-value: 1Fisher Exact
p-value: 1Fisher Exact