Neuropathic Pain
Conditions
Keywords
Analgesic effect
Brief summary
A study to investigate the analgesic efficacy of AZD2423 compared with placebo after 28 days treatment in patients with painful diabetic polyneuropathy.
Interventions
DRUGAZD2423
20 mg tablet
DRUGPlacebo
Placebo
Sponsors
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 signed informed consent form * Males and female of non-child bearing potential patients aged 18 to 80 years * Patients with neuropathic pain due to painful diabetic polyneuropathy.
Exclusion criteria
* Other pain that may confound assessment of neuropathic pain * History of treatment failure with more than three adequate trials of medication for neuropathic pain * Central neuropathic pain conditions (caused by Central Nervous System injury/disease, eg. Stroke)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain Score. | Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28 | Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Average Pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10; 0=No pain, 10=Worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain Score. | Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28 | Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Worst pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10, 0=No pain, 10=Worst pain imaginable. |
| Number of Participants With at Least 30% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | Baseline (mean of Day -5 to Day -1) to Day 28 | Last Observation Carried Forward (LOCF). Numerical Rating Scale(NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)\*100. Responder= NRS Average Pain score reduction ≥30% (yes/no) |
| Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | Baseline (mean of Day -5 to Day -1) to Day 28 | Last Observation Carried Forward (LOCF). Numerical Rating Scale (NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)\*100. Responder= NRS Average Pain score reduction ≥50% (yes/no) |
| Change From Baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total Score. | Baseline (Day 1) to Day 29 (Visit 7) | Last Observation carried Forward (LOCF). Scale consists of 10 Neuropathic Pain Symptom Inventory Scale (NPSI) pain symptom descriptors wiht a recall period of 24 hours. Each descriptor is rated on a Numerical Rating Scale (NRS) 0-10; 0=No (symptom), 10=Worst (symptom) imaginable. The NPSI Total Score was calculated as the sum of 10 of the NPSI descriptors. Range for total score 0 -100. Higher total score implicates worse symptoms. |
Countries
Canada, United States
Participant flow
Recruitment details
The first participant was enrolled on 20th September 2010 and the last participant completed on 6th June 2011. A total of 20 centres in United States (US) and Canada randomised 134 participants.
Pre-assignment details
The study had an enrolment phase of up to 35 days (including wash-out and baseline periods), a 28-day treatment phase, and a follow-up phase of 7-14 days. Participants were randomly assigned to blinded treatment in a 1:1:1 ratio either to AZD2423 20 mg, AZD2423 150 mg or placebo.
Participants by arm
| Arm | Count |
|---|---|
| AZD2423 150 mg tablets, 150 mg once daily in the morning | 48 |
| AZD2423 20 mg tablets, 20 mg once daily in the morning | 45 |
| Placebo tablets, once daily in the morning | 41 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 2 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Decrease in renal function | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Painful Diabetic Neuropathy worsening | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Safety, possible history of tuberculosis | 0 | 0 | 1 |
| Overall Study | Screen failure | 1 | 1 | 0 |
| Overall Study | Study-specific withdrawal criteria | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 0 | 3 |
Baseline characteristics
| Characteristic | AZD2423 150 mg | AZD2423 20 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 57.8 Years STANDARD_DEVIATION 6.9 | 59.6 Years STANDARD_DEVIATION 8.4 | 56.4 Years STANDARD_DEVIATION 8.4 | 58 Years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 23 Participants | 22 Participants | 20 Participants | 65 Participants |
| Sex: Female, Male Male | 25 Participants | 23 Participants | 21 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 47 | 6 / 44 | 11 / 41 |
| serious Total, serious adverse events | 0 / 47 | 3 / 44 | 0 / 41 |
Outcome results
Primary
Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain Score.
Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Average Pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10; 0=No pain, 10=Worst pain imaginable.
Time frame: Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28
Population: Intention-to-treat set (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 150 mg | Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain Score. | -1.35 Scores on a scale | Standard Deviation 1.89 |
| AZD2423 20 mg | Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain Score. | -1.50 Scores on a scale | Standard Deviation 1.77 |
| Placebo | Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain Score. | -1.61 Scores on a scale | Standard Deviation 2.26 |
Secondary
Change From Baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total Score.
Last Observation carried Forward (LOCF). Scale consists of 10 Neuropathic Pain Symptom Inventory Scale (NPSI) pain symptom descriptors wiht a recall period of 24 hours. Each descriptor is rated on a Numerical Rating Scale (NRS) 0-10; 0=No (symptom), 10=Worst (symptom) imaginable. The NPSI Total Score was calculated as the sum of 10 of the NPSI descriptors. Range for total score 0 -100. Higher total score implicates worse symptoms.
Time frame: Baseline (Day 1) to Day 29 (Visit 7)
Population: Modified Intention- to- treat set (ITT) including only patients with adequate baseline and Day 29 data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 150 mg | Change From Baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total Score. | -14.63 Scores on a scale | Standard Deviation 22.77 |
| AZD2423 20 mg | Change From Baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total Score. | -12.20 Scores on a scale | Standard Deviation 22.84 |
| Placebo | Change From Baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total Score. | -7.82 Scores on a scale | Standard Deviation 17.02 |
Secondary
Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain Score.
Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Worst pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10, 0=No pain, 10=Worst pain imaginable.
Time frame: Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28
Population: Intention-to-treat set (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD2423 150 mg | Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain Score. | -1.57 Scores on a scale | Standard Deviation 1.96 |
| AZD2423 20 mg | Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain Score. | -1.66 Scores on a scale | Standard Deviation 2.06 |
| Placebo | Change From Baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain Score. | -1.80 Scores on a scale | Standard Deviation 2.48 |
Secondary
Number of Participants With at Least 30% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28.
Last Observation Carried Forward (LOCF). Numerical Rating Scale(NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)\*100. Responder= NRS Average Pain score reduction ≥30% (yes/no)
Time frame: Baseline (mean of Day -5 to Day -1) to Day 28
Population: Intention-to-treat set (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2423 150 mg | Number of Participants With at Least 30% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | 16 Participants |
| AZD2423 20 mg | Number of Participants With at Least 30% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | 19 Participants |
| Placebo | Number of Participants With at Least 30% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | 15 Participants |
Secondary
Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28.
Last Observation Carried Forward (LOCF). Numerical Rating Scale (NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)\*100. Responder= NRS Average Pain score reduction ≥50% (yes/no)
Time frame: Baseline (mean of Day -5 to Day -1) to Day 28
Population: Intention-to-treat set (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2423 150 mg | Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | 10 Participants |
| AZD2423 20 mg | Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | 8 Participants |
| Placebo | Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. | 10 Participants |