Trial Outcomes & Findings for Eslicarbazepine Acetate as Therapy in Diabetic Neuropathic Pain (NCT NCT01129960)
NCT ID: NCT01129960
Last Updated: 2014-07-18
Results Overview
Study was prematurely halted. The efficacy analysis was restricted to the primary efficacy variable in the interim analysis population. The intended treatment period, starting on the day of the randomization and ending at the efficacy cut-off date (31st October 2011), was the basis for the efficacy analysis; patients with less than 20 days of study medication were excluded from the analysis, except those with early discontinuation. Primary efficacy variable was the difference between the mean values of 7 daily pain scores preceding the efficacy cut-off date (endpoint mean pain score), and before randomization (baseline mean pain score), respectively. The daily pain scores were based on the morning response to the 11-point Numeric Rating Pain Scale (NRPS) question relating to average pain intensity over the last 24 hours. The NPRS is an 11-point scale from 0-10 \["0" = no pain; "10" = the most intense pain imaginable\]
TERMINATED
PHASE3
332 participants
baseline up to endpoint 15 weeks (3-week titration phase and 12-week treatment maintenance phase)
2014-07-18
Participant Flow
Fifty nine (59) clinical sites in 10 countries Study period: Date of first admission: 2010.12.06 Date of last visit: 2012.04.24
Participant milestones
| Measure |
Esl 1600 mg
Eslicarbazepine acetate (Esl) (BIA 2-093) mg once daily (QD): Tablets will be used.
|
Esl 1200 mg
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Esl 800 mg
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Placebo
Placebo: Tablets will be used.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
84
|
83
|
82
|
83
|
|
Overall Study
Safety
|
84
|
83
|
83
|
82
|
|
Overall Study
Intent-to-Treat
|
84
|
83
|
82
|
83
|
|
Overall Study
Per-Protocol
|
34
|
52
|
49
|
55
|
|
Overall Study
Full Analysis Set (FAS
|
71
|
67
|
68
|
71
|
|
Overall Study
COMPLETED
|
54
|
61
|
56
|
70
|
|
Overall Study
NOT COMPLETED
|
30
|
22
|
26
|
13
|
Reasons for withdrawal
| Measure |
Esl 1600 mg
Eslicarbazepine acetate (Esl) (BIA 2-093) mg once daily (QD): Tablets will be used.
|
Esl 1200 mg
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Esl 800 mg
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Placebo
Placebo: Tablets will be used.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
3
|
2
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
1
|
1
|
|
Overall Study
Adverse Event
|
23
|
16
|
16
|
7
|
|
Overall Study
Protocol Violation
|
1
|
2
|
3
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
3
|
3
|
|
Overall Study
Discontinuation of the study by Sponsor
|
0
|
1
|
0
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
0
|
|
Overall Study
Pregnancy
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Eslicarbazepine Acetate as Therapy in Diabetic Neuropathic Pain
Baseline characteristics by cohort
| Measure |
Esl 1600 mg
n=84 Participants
Eslicarbazepine acetate (Esl) (BIA 2-093) mg once daily (QD): Tablets will be used.
|
Esl 1200 mg
n=83 Participants
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Esl 800 mg
n=83 Participants
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Placebo
n=82 Participants
Placebo: Tablets will be used.
|
Total
n=332 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
57.6 years
STANDARD_DEVIATION 10.93 • n=99 Participants
|
59.0 years
STANDARD_DEVIATION 11.38 • n=107 Participants
|
58.0 years
STANDARD_DEVIATION 13.33 • n=206 Participants
|
59.5 years
STANDARD_DEVIATION 10.25 • n=7 Participants
|
58.5 years
STANDARD_DEVIATION 11.51 • n=31 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
33 Participants
n=7 Participants
|
150 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
46 Participants
n=206 Participants
|
49 Participants
n=7 Participants
|
182 Participants
n=31 Participants
|
|
Race/Ethnicity, Customized
White
|
55 participants
n=99 Participants
|
50 participants
n=107 Participants
|
55 participants
n=206 Participants
|
50 participants
n=7 Participants
|
210 participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Black
|
2 participants
n=99 Participants
|
3 participants
n=107 Participants
|
1 participants
n=206 Participants
|
2 participants
n=7 Participants
|
8 participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Asian
|
26 participants
n=99 Participants
|
28 participants
n=107 Participants
|
25 participants
n=206 Participants
|
24 participants
n=7 Participants
|
103 participants
n=31 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=99 Participants
|
2 participants
n=107 Participants
|
2 participants
n=206 Participants
|
6 participants
n=7 Participants
|
11 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: baseline up to endpoint 15 weeks (3-week titration phase and 12-week treatment maintenance phase)Population: FAS = Full Analysis Set (comprised all randomized subjects with mean pain score at baseline and mean score after randomization; subjects with less than 20 days of study medication of the cut-off date were excluded from the dataset, except those that prematurely withdrew; this was the primary population used in the efficacy analysis)
Study was prematurely halted. The efficacy analysis was restricted to the primary efficacy variable in the interim analysis population. The intended treatment period, starting on the day of the randomization and ending at the efficacy cut-off date (31st October 2011), was the basis for the efficacy analysis; patients with less than 20 days of study medication were excluded from the analysis, except those with early discontinuation. Primary efficacy variable was the difference between the mean values of 7 daily pain scores preceding the efficacy cut-off date (endpoint mean pain score), and before randomization (baseline mean pain score), respectively. The daily pain scores were based on the morning response to the 11-point Numeric Rating Pain Scale (NRPS) question relating to average pain intensity over the last 24 hours. The NPRS is an 11-point scale from 0-10 \["0" = no pain; "10" = the most intense pain imaginable\]
Outcome measures
| Measure |
Esl 1600 mg
n=71 Participants
Eslicarbazepine acetate (Esl) (BIA 2-093) mg once daily (QD): Tablets will be used.
|
Esl 1200 mg
n=67 Participants
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Esl 800 mg
n=68 Participants
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Placebo
n=71 Participants
Placebo: Tablets will be used.
|
|---|---|---|---|---|
|
Change From Baseline to Endpoint in Mean Pain
|
-1.56 units on a scale
Standard Error 0.232
|
-0.90 units on a scale
Standard Error 0.237
|
-1.73 units on a scale
Standard Error 0.236
|
-1.13 units on a scale
Standard Error 0.231
|
Adverse Events
Esl 1600 mg
Esl 1200 mg
Esl 800 mg
Placebo
Serious adverse events
| Measure |
Esl 1600 mg
n=84 participants at risk
Eslicarbazepine acetate (Esl) (BIA 2-093) mg once daily (QD): Tablets will be used.
|
Esl 1200 mg
n=83 participants at risk
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Esl 800 mg
n=83 participants at risk
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Placebo
n=82 participants at risk
Placebo: Tablets will be used.
|
|---|---|---|---|---|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Cardiac disorders
Cardiac arrest
|
1.2%
1/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Cardiac disorders
Myocardial infarction
|
1.2%
1/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Cardiac disorders
Ventricular tachycardia
|
1.2%
1/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Gastrointestinal disorders
Haemorrhoida haemorrhage
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/82 • Throughout the study
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/82 • Throughout the study
|
|
Infections and infestations
Diabetic foot infection
|
1.2%
1/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Infections and infestations
Pneumonia
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/82 • Throughout the study
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/84 • Throughout the study
|
1.2%
1/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.4%
2/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/82 • Throughout the study
|
|
Nervous system disorders
Cerebrovascular accident
|
1.2%
1/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Nervous system disorders
Senile dementia
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/82 • Throughout the study
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.2%
1/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/82 • Throughout the study
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/84 • Throughout the study
|
1.2%
1/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Vascular disorders
Accelerated hypertension
|
1.2%
1/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/84 • Throughout the study
|
1.2%
1/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.00%
0/84 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
0.00%
0/83 • Throughout the study
|
1.2%
1/82 • Throughout the study
|
Other adverse events
| Measure |
Esl 1600 mg
n=84 participants at risk
Eslicarbazepine acetate (Esl) (BIA 2-093) mg once daily (QD): Tablets will be used.
|
Esl 1200 mg
n=83 participants at risk
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Esl 800 mg
n=83 participants at risk
Eslicarbazepine acetate (BIA 2-093) mg QD: Tablets will be used.
|
Placebo
n=82 participants at risk
Placebo: Tablets will be used.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
9.5%
8/84 • Throughout the study
|
6.0%
5/83 • Throughout the study
|
12.0%
10/83 • Throughout the study
|
4.9%
4/82 • Throughout the study
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
10.7%
9/84 • Throughout the study
|
8.4%
7/83 • Throughout the study
|
2.4%
2/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Ear and labyrinth disorders
Vertigo
|
10.7%
9/84 • Throughout the study
|
7.2%
6/83 • Throughout the study
|
2.4%
2/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Nervous system disorders
Somnolence
|
3.6%
3/84 • Throughout the study
|
9.6%
8/83 • Throughout the study
|
4.8%
4/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Nervous system disorders
Dizziness
|
7.1%
6/84 • Throughout the study
|
3.6%
3/83 • Throughout the study
|
6.0%
5/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Nervous system disorders
Headache
|
7.1%
6/84 • Throughout the study
|
2.4%
2/83 • Throughout the study
|
7.2%
6/83 • Throughout the study
|
4.9%
4/82 • Throughout the study
|
|
Gastrointestinal disorders
Vomiting
|
7.1%
6/84 • Throughout the study
|
3.6%
3/83 • Throughout the study
|
3.6%
3/83 • Throughout the study
|
0.00%
0/82 • Throughout the study
|
|
Investigations
Hypertension
|
7.1%
6/84 • Throughout the study
|
4.8%
4/83 • Throughout the study
|
3.6%
3/83 • Throughout the study
|
2.4%
2/82 • Throughout the study
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER