Neuropathic Pain, Mechanical Hypersensitivity
Conditions
Keywords
Pain, Mechanical Hypersensitivity, Allodynia, Efficacy, analgesia, Neuropathic
Brief summary
The purpose of this study is to investigate if 28 days of treatment with AZD2066 compared to placebo can relieve the pain arising from the nervous system when the patients are touched by something that should not cause pain or have severe pain when they are touched by something that should only cause a little pain.
Interventions
DRUGAZD2066
Capsule, once daily
DRUGPlacebo
Capsule, once daily
Sponsors
Quintiles, Inc.
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Provision of informed consent prior to any study specific procedures. * Male or non-fertile females * Painful symptoms due to neuropathic pain for a period of 3 months to 5 years, associated with mechanical allodynia and/or punctate hyperalgesia.
Exclusion criteria
* Other pain that may confound assessment of neuropathic pain. * Diagnosis of any severe neurological disease. * History of significant psychiatric disease/condition and/or history of psychotic disorders among first degree relatives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Numerical Rating Scale (NRS) Pain Score From Baseline to Last 5 Days on Treatment | Change in mean pain intensity from 5-day baseline to the last 5 days on treatment, measure twice daily with NRS (12-hour recall) | Mean pain intensity for 5-day baseline period (morning Day -5 to evening Day-1) and mean pain intensity for last 5 days on treatment (ie, last dose day and the 4 preceding calendar days) was calculated based on the NRS scale (0-10). 0=No pain, 10=Worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients With ≥50% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 | 28 days | Pain intensity score reduction=(change from baseline Day 28/baseline)\*100 Responder=pain intensity score reduction ≥50% (Yes/No)? Responder rate=(no. of responders/total no. of patients)\*100 |
| Patients With Patient Global Impression of Change (PGIC) Score of at Least Much Improved (Responder Rate) at Day 28 | 28 days | PGIC scale ranges from 1-7 where 1=Very much improved and 7=Very much worse Responder=Patient with a response of much improved or very much improved Responder rate=(no. of responders/total no. of patients)\*100 |
| Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index From Baseline to Day 28 | 28 days | Sensory index=sum of the intensity scale values of the words chosen for the descriptors 1-11 in the questionnaire. Range of scores for the sensory index=0-33 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated. |
| Patients With ≥30% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 | 28 days | NRS pain intensity score reduction=(change from baseline at Day 28/baseline)\*100 Responder=pain intensity score reduction ≥30% (yes/no)? Responder rate=(no. of responders/total no. of patients)\*100 |
| Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28 | 28 days | Change from baseline (measured prior to randomization) to Day 28 was calculated for the pain severity (mean of 4 intensity items). Each intensity item is recorded on a NRS 0-10, where 0=No Pain and 10=Pain as bad as you can imagine. |
| Change in BPI-SF Pain Interference From Baseline to Day 28 | 28 days | Change from baseline (measured prior to randomization) to Day 28 was calculated for pain interference (mean of 7 interference items). Each interference item is recorded on a NRS 0-10, where 0=No interference and 10=Interferes completely. |
| Change in SF-MPQ Affective Index From Baseline to Day 28 | 28 days | Affective index=sum of the intensity scale values of the words chosen for the descriptors 12-15 in the questionnaire. Range of scores for the affective index=0-12 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated. |
Countries
United States
Participant flow
Recruitment details
This multicenter study was conducted between August 2009 and November 2010 in the United States.
Pre-assignment details
The study had an enrolment phase of up to 35 days (including washout and baseline periods), a 28-day treatment phase, and a follow-up phase of 7 days (for men and women not of childbearing potential) or 28 days (for women of childbearing potential). Patients randomized to AZD2066 received AZD2066 12 mg from Days 1 to 4 and 18 mg from Days 5 to 28.
Participants by arm
| Arm | Count |
|---|---|
| A - AZD2066 AZD2066, 12 mg capsule | 42 |
| 2 - Placebo Placebo, capsule | 45 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal ECG findings | 1 | 0 |
| Overall Study | Adverse Event | 9 | 0 |
| Overall Study | Eligibility criteria not fulfilled | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Severe non-compliance to protocol | 0 | 1 |
| Overall Study | Study stopped by sponsor | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 6 |
Baseline characteristics
| Characteristic | A - AZD2066 | 2 - Placebo | Total |
|---|---|---|---|
| Age Continuous | 58.1 years STANDARD_DEVIATION 9.25 | 59.3 years STANDARD_DEVIATION 14.31 | 58.7 years STANDARD_DEVIATION 12.8 |
| Sex: Female, Male Female | 24 Participants | 18 Participants | 42 Participants |
| Sex: Female, Male Male | 18 Participants | 27 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 42 | 15 / 44 |
| serious Total, serious adverse events | 1 / 42 | 0 / 44 |
Outcome results
Primary
Change in Mean Numerical Rating Scale (NRS) Pain Score From Baseline to Last 5 Days on Treatment
Mean pain intensity for 5-day baseline period (morning Day -5 to evening Day-1) and mean pain intensity for last 5 days on treatment (ie, last dose day and the 4 preceding calendar days) was calculated based on the NRS scale (0-10). 0=No pain, 10=Worst pain imaginable.
Time frame: Change in mean pain intensity from 5-day baseline to the last 5 days on treatment, measure twice daily with NRS (12-hour recall)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A - AZD2066 | Change in Mean Numerical Rating Scale (NRS) Pain Score From Baseline to Last 5 Days on Treatment | -2.14 Scores (units) on NRS | Standard Error 0.358 |
| 2 - Placebo | Change in Mean Numerical Rating Scale (NRS) Pain Score From Baseline to Last 5 Days on Treatment | -1.26 Scores (units) on NRS | Standard Error 0.337 |
Secondary
Change in BPI-SF Pain Interference From Baseline to Day 28
Change from baseline (measured prior to randomization) to Day 28 was calculated for pain interference (mean of 7 interference items). Each interference item is recorded on a NRS 0-10, where 0=No interference and 10=Interferes completely.
Time frame: 28 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A - AZD2066 | Change in BPI-SF Pain Interference From Baseline to Day 28 | -1.98 Scores on BPI-SF pain interference | Standard Error 0.376 |
| 2 - Placebo | Change in BPI-SF Pain Interference From Baseline to Day 28 | -1.72 Scores on BPI-SF pain interference | Standard Error 0.36 |
Secondary
Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28
Change from baseline (measured prior to randomization) to Day 28 was calculated for the pain severity (mean of 4 intensity items). Each intensity item is recorded on a NRS 0-10, where 0=No Pain and 10=Pain as bad as you can imagine.
Time frame: 28 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A - AZD2066 | Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28 | -2.12 Scores (units) on BPI-SF pain severity | Standard Error 0.385 |
| 2 - Placebo | Change in Brief Pain Inventory-Short Form (BPI-SF) Pain Severity From Baseline to Day 28 | -1.25 Scores (units) on BPI-SF pain severity | Standard Error 0.36 |
Secondary
Change in SF-MPQ Affective Index From Baseline to Day 28
Affective index=sum of the intensity scale values of the words chosen for the descriptors 12-15 in the questionnaire. Range of scores for the affective index=0-12 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated.
Time frame: 28 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A - AZD2066 | Change in SF-MPQ Affective Index From Baseline to Day 28 | -1.1 Scores (units) on SF-MPQ Affective Index | Standard Deviation 0.52 |
| 2 - Placebo | Change in SF-MPQ Affective Index From Baseline to Day 28 | -0.9 Scores (units) on SF-MPQ Affective Index | Standard Deviation 0.5 |
Secondary
Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index From Baseline to Day 28
Sensory index=sum of the intensity scale values of the words chosen for the descriptors 1-11 in the questionnaire. Range of scores for the sensory index=0-33 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated.
Time frame: 28 days
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A - AZD2066 | Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index From Baseline to Day 28 | -6.39 Scores (units) on SF-MPQ Sensory Index | Standard Error 1.278 |
| 2 - Placebo | Change in Short Form McGill Pain Questionnaire (SF-MPQ) Sensory Index From Baseline to Day 28 | -3.98 Scores (units) on SF-MPQ Sensory Index | Standard Error 1.188 |
Secondary
Patients With ≥30% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28
NRS pain intensity score reduction=(change from baseline at Day 28/baseline)\*100 Responder=pain intensity score reduction ≥30% (yes/no)? Responder rate=(no. of responders/total no. of patients)\*100
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - AZD2066 | Patients With ≥30% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 | 16 Participants |
| 2 - Placebo | Patients With ≥30% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 | 10 Participants |
Secondary
Patients With ≥50% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28
Pain intensity score reduction=(change from baseline Day 28/baseline)\*100 Responder=pain intensity score reduction ≥50% (Yes/No)? Responder rate=(no. of responders/total no. of patients)\*100
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - AZD2066 | Patients With ≥50% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 | 10 Participants |
| 2 - Placebo | Patients With ≥50% Reduction From Baseline in NRS Pain Intensity Score (Responder Rate) at Day 28 | 5 Participants |
Secondary
Patients With Patient Global Impression of Change (PGIC) Score of at Least Much Improved (Responder Rate) at Day 28
PGIC scale ranges from 1-7 where 1=Very much improved and 7=Very much worse Responder=Patient with a response of much improved or very much improved Responder rate=(no. of responders/total no. of patients)\*100
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - AZD2066 | Patients With Patient Global Impression of Change (PGIC) Score of at Least Much Improved (Responder Rate) at Day 28 | 10 Patients |
| 2 - Placebo | Patients With Patient Global Impression of Change (PGIC) Score of at Least Much Improved (Responder Rate) at Day 28 | 10 Patients |