Painful Diabetic Neuropathy
Conditions
Keywords
pain diabetes neuropathy
Brief summary
The primary objective of the study is to assess the efficacy of eslicarbazepine acetate (ESL) as therapy for patients with painful diabetic neuropathy.
Interventions
Eslicarbazepine acetate tablets, scored to allow dose titration during the titration period.
DRUGPlacebo
oral route
Sponsors
Bial - Portela C S.A.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent to participate in the study * Men and women aged 18 years or older * Diagnosis of diabetes mellitus Type 1 or 2 * Diagnosis of pain attributed to diabetic neuropathy for more than 1 year prior to enrolment * Stable glycemic control: (total glycated haemoglobin \[HbA1c\] level ≤ 11% at screening) * Cooperation and willingness to complete all aspects of the study * Completion of at least 4 daily diaries during the week preceding randomisation * A minimum average daily pain score of 4 on the Numeric rating pain scale (NRPS) in the last 4 diary entries before randomisation.
Exclusion criteria
* Pain of other origin that might confound the assessment of neuropathic pain of diabetic origin * Significant or unstable medical or psychiatric disorders * Drug or alcohol abuse in the preceding 2 years * Peripheral vascular disease with a history of amputation, except amputation of toes * Severe renal function impairment, as shown by calculated creatinine clearance values \< 30 mL/min at screening * Relevant clinical laboratory abnormalities (e.g., Na+ \<130 mmol/L, alanine (ALT) or aspartate (AST) transaminases \>2.0 times the upper limit of normal, white blood cell count (WBC) \<2,500 cells/mm3) * Previous participation in any study with eslicarbazepine acetate * Pregnancy or breast feeding * History of hypersensitivity to the investigational products or to drugs with a similar chemical structure * History of non-compliance * Likelihood of requiring treatment during the study period with drugs or other interventions not permitted by the clinical study protocol. * Participation in a clinical study within 3 months prior to screening * Any clinically significant concomitant condition, which might influence the assessments or conduct of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain | 17 weeks | Endpoint mean pain was defined as the mean of the last 4 available pain scores in the last 7 days of the treatment period. Likewise, baseline mean pain was defined as the mean of the last 4 available pain scores in the last 7 days of the baseline period. |
Participant flow
Recruitment details
Date first subject enrolled: 06 Nov 2007 Date last subject completed: 18 Nov 2008 Randomised and treated: 557. Analyzed for efficacy (per-protocol \[PP\]): 403. Analyzed for safety: 557.
Pre-assignment details
During the 2week baseline period,current neuropathic pain drug therapy was discontinued and subjects had to be free of any medication that could affect efficacy(except authorized rescue medication)for 2weeks before start of double-blind study treatment.In case of unbearable pain, this drug-free period could be reduced,but had to be at least 7 days.
Participants by arm
| Arm | Count |
|---|---|
| ESL 1200 mg QD Eslicarbazepine acetate 1200 mg once daily
Eslicarbazepine acetate : Eslicarbazepine acetate tablets, scored to allow dose titration during the titration period. | 85 |
| ESL 400 mg BD ESL 400 mg twice daily
Eslicarbazepine acetate : Eslicarbazepine acetate tablets, scored to allow dose titration during the titration period. | 89 |
| ESL 600 mg BID Eslicarbazepine 600 mg twice daily
Eslicarbazepine acetate : Eslicarbazepine acetate tablets, scored to allow dose titration during the titration period. | 95 |
| ESL 800 mg BID Eslicarbazepine acetate 800 mg twice daily
Eslicarbazepine acetate : Eslicarbazepine acetate tablets, scored to allow dose titration during the titration period. | 100 |
| ESL 800 mg QD ESL 800 mg once-daily
Eslicarbazepine acetate : Eslicarbazepine acetate tablets, scored to allow dose titration during the titration period. | 92 |
| Placebo Placebo
Placebo : oral route | 96 |
| Total | 557 |
Baseline characteristics
| Characteristic | ESL 1200 mg QD | ESL 400 mg BD | ESL 600 mg BID | ESL 800 mg BID | ESL 800 mg QD | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 32 participants | 28 participants | 34 participants | 39 participants | 33 participants | 31 participants | 197 participants |
| Age, Customized Between 18 and 65 years | 53 participants | 61 participants | 61 participants | 61 participants | 59 participants | 65 participants | 360 participants |
| Sex: Female, Male Female | 42 Participants | 48 Participants | 56 Participants | 56 Participants | 50 Participants | 57 Participants | 309 Participants |
| Sex: Female, Male Male | 43 Participants | 41 Participants | 39 Participants | 44 Participants | 42 Participants | 39 Participants | 248 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 85 | 0 / 89 | 23 / 95 | 35 / 100 | 0 / 92 | 6 / 96 |
| serious Total, serious adverse events | 7 / 85 | 3 / 89 | 0 / 95 | 4 / 100 | 1 / 92 | 0 / 96 |
Outcome results
Primary
Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain
Endpoint mean pain was defined as the mean of the last 4 available pain scores in the last 7 days of the treatment period. Likewise, baseline mean pain was defined as the mean of the last 4 available pain scores in the last 7 days of the baseline period.
Time frame: 17 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ESL 1200 mg QD | Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain | -1.7546 units on a scale | Standard Error 0.2352 |
| ESL 400 mg BD | Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain | -2.2865 units on a scale | Standard Error 0.2325 |
| ESL 600 mg BID | Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain | -1.6746 units on a scale | Standard Error 0.2312 |
| ESL 800 mg BID | Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain | -1.8353 units on a scale | Standard Error 0.226 |
| ESL 800 mg QD | Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain | -1.9829 units on a scale | Standard Error 0.2328 |
| Placebo | Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain | -1.5801 units on a scale | Standard Error 0.2311 |