Trial Outcomes & Findings for Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) in Acute Manic Episodes Associated With Bipolar I Disorder (NCT NCT01822678)
NCT ID: NCT01822678
Last Updated: 2014-03-27
Results Overview
The YMRS is used to assess disease severity in patients who have been previously diagnosed with mania and it has proven psychometric properties through 11 item multiple-choice diagnostic questionnaire and the total score is determined from the summation of each 11 individual scores (and can range from 0 - 60) based on the patient's subjective feedback of his clinical condition over the previous 48 hours. A higher score indicates a worse rating for symptoms related to mania. At every visit throughout the study, investigators administered the YMRS. The results of the primary analysis of efficacy were calculated using Analysis of covariance (ANCOVA) with Last Observation Carried Forward (LOCF). Primary variable is presented through ANCOVA results for absolute change in YMRS total score from baseline (V2) to end of treatment (V7). A responder has at least 50% improvement (reduction) in the YMRS total score or has a total score of less than 12 points at the end of treatment period.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
161 participants
Primary outcome timeframe
baseline and 3-week
Results posted on
2014-03-27
Participant Flow
Study centres: 23 centres: 2 centres in Austria, 6 centres in Czech Republic, 6 centres in Slovakia, 1 centre in Portugal, and 8 centres in Romania. First patient enrolled: 02 December 2005 Last patient completed: 23 November 2006
Patients who met the selection criteria at the randomisation visit (visit 2, Day 1) were randomised to 1 of the 3 treatment groups
Participant milestones
| Measure |
ESL 800 mg
Group 1: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
|
ESL 600 mg
Group 2: Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
|
Placebo
Group 3: Placebo (change in daily number of tablets administered, according to clinical response).
Placebo : Placebo, sugar pill
|
|---|---|---|---|
|
Overall Study
STARTED
|
57
|
64
|
40
|
|
Overall Study
Treated
|
57
|
64
|
40
|
|
Overall Study
Safety Population
|
57
|
64
|
40
|
|
Overall Study
Intention-to-Treat Population (ITT)
|
57
|
63
|
40
|
|
Overall Study
Per Protocol Population
|
45
|
52
|
34
|
|
Overall Study
COMPLETED
|
45
|
49
|
29
|
|
Overall Study
NOT COMPLETED
|
12
|
15
|
11
|
Reasons for withdrawal
| Measure |
ESL 800 mg
Group 1: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
|
ESL 600 mg
Group 2: Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
|
Placebo
Group 3: Placebo (change in daily number of tablets administered, according to clinical response).
Placebo : Placebo, sugar pill
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
4
|
4
|
|
Overall Study
Adverse Event
|
4
|
3
|
1
|
|
Overall Study
Lack of Efficacy
|
3
|
6
|
5
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
1
|
Baseline Characteristics
Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) in Acute Manic Episodes Associated With Bipolar I Disorder
Baseline characteristics by cohort
| Measure |
BIA 2-093 - 2400 mg (Maximum Dose)
n=57 Participants
Group 1: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
|
BIA 2-093 - 1800 mg (Maximum Dose)
n=64 Participants
Group 2: Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
|
Placebo
n=40 Participants
Group 3: Placebo (change in daily number of tablets administered, according to clinical response).
Placebo : Placebo, sugar pill
|
Total
n=161 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
18 - 20 Years
|
2 participants
19.3 • n=5 Participants
|
0 participants
14.3 • n=7 Participants
|
0 participants
22.5 • n=5 Participants
|
2 participants
12.98 • n=4 Participants
|
|
Age, Customized
20 - 30 Years
|
9 participants
70.2 • n=5 Participants
|
10 participants
76.2 • n=7 Participants
|
9 participants
67.85 • n=5 Participants
|
28 participants
12.79 • n=4 Participants
|
|
Age, Customized
30 - 40 Years
|
15 participants
10.5 • n=5 Participants
|
17 participants
9.5 • n=7 Participants
|
8 participants
10.0 • n=5 Participants
|
40 participants
13.19 • n=4 Participants
|
|
Age, Customized
40 - 50 Years
|
15 participants
n=5 Participants
|
16 participants
n=7 Participants
|
11 participants
n=5 Participants
|
42 participants
n=4 Participants
|
|
Age, Customized
50 - 60 Years
|
10 participants
n=5 Participants
|
15 participants
n=7 Participants
|
8 participants
n=5 Participants
|
33 participants
n=4 Participants
|
|
Age, Customized
60 - 70 Years
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
3 participants
n=5 Participants
|
14 participants
n=4 Participants
|
|
Age, Customized
70 - 80 Years
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
81 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
80 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: baseline and 3-weekPopulation: The ITT efficacy population consisted of all randomised patients who received at least one dose of investigational product and at least 1 post-baseline YMRS assessment. If a patient discontinues before the end of the 3-week treatment period then the last observation will be carried forward (LOCF).
The YMRS is used to assess disease severity in patients who have been previously diagnosed with mania and it has proven psychometric properties through 11 item multiple-choice diagnostic questionnaire and the total score is determined from the summation of each 11 individual scores (and can range from 0 - 60) based on the patient's subjective feedback of his clinical condition over the previous 48 hours. A higher score indicates a worse rating for symptoms related to mania. At every visit throughout the study, investigators administered the YMRS. The results of the primary analysis of efficacy were calculated using Analysis of covariance (ANCOVA) with Last Observation Carried Forward (LOCF). Primary variable is presented through ANCOVA results for absolute change in YMRS total score from baseline (V2) to end of treatment (V7). A responder has at least 50% improvement (reduction) in the YMRS total score or has a total score of less than 12 points at the end of treatment period.
Outcome measures
| Measure |
BIA 2-093 - 2400 mg (Maximum Dose)
n=57 Participants
Group 1: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
|
BIA 2-093 - 1800 mg (Maximum Dose)
n=63 Participants
Group 2: Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
|
Placebo
n=40 Participants
Group 3: Placebo (change in daily number of tablets administered, according to clinical response).
Placebo : Placebo, sugar pill
|
|---|---|---|---|
|
Change in the Young Mania Rating Scale (YMRS) Total Score at the End of the 3-week Treatment Period, in Relation to the Baseline.
|
-14.2 units on a scale
Standard Error 1.17
|
-12.5 units on a scale
Standard Error 1.12
|
-10.3 units on a scale
Standard Error 1.40
|
Adverse Events
BIA 2-093 - 2400 mg (Maximum Dose)
Serious events: 2 serious events
Other events: 20 other events
Deaths: 0 deaths
BIA 2-093 - 1800 mg (Maximum Dose)
Serious events: 2 serious events
Other events: 25 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BIA 2-093 - 2400 mg (Maximum Dose)
n=57 participants at risk
Group 1: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
|
BIA 2-093 - 1800 mg (Maximum Dose)
n=64 participants at risk
Group 2: Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
|
Placebo
n=40 participants at risk
Group 3: Placebo (change in daily number of tablets administered, according to clinical response).
Placebo : Placebo, sugar pill
|
|---|---|---|---|
|
Psychiatric disorders
Mania
|
3.5%
2/57 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
1.6%
1/64 • Number of events 1 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
0.00%
0/40 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/57 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
1.6%
1/64 • Number of events 1 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
0.00%
0/40 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/57 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
1.6%
1/64 • Number of events 1 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
0.00%
0/40 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/57 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
0.00%
0/64 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
2.5%
1/40 • Number of events 1 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
Other adverse events
| Measure |
BIA 2-093 - 2400 mg (Maximum Dose)
n=57 participants at risk
Group 1: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.
|
BIA 2-093 - 1800 mg (Maximum Dose)
n=64 participants at risk
Group 2: Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
Eslicarbazepine Acetate : Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
|
Placebo
n=40 participants at risk
Group 3: Placebo (change in daily number of tablets administered, according to clinical response).
Placebo : Placebo, sugar pill
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
8.8%
5/57 • Number of events 5 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
10.9%
7/64 • Number of events 7 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
0.00%
0/40 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
Nervous system disorders
Dizziness
|
8.8%
5/57 • Number of events 5 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
9.4%
6/64 • Number of events 6 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
10.0%
4/40 • Number of events 4 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
General disorders
Nausea
|
7.0%
4/57 • Number of events 4 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
3.1%
2/64 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
5.0%
2/40 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
Gastrointestinal disorders
Vomiting
|
3.5%
2/57 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
6.2%
4/64 • Number of events 4 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
5.0%
2/40 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
Gastrointestinal disorders
Diarrhoea
|
3.5%
2/57 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
6.2%
4/64 • Number of events 4 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
0.00%
0/40 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
|
Psychiatric disorders
Agitation
|
3.5%
2/57 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
3.1%
2/64 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
5.0%
2/40 • Number of events 2 • Up to 4 weeks
Participants were followed for the duration of drug administration, an average of 4 weeks (titration and maintenance) plus up to 6 days (tapering-off, i.e. downtitration conducted on an individual basis corresponding to up-titration)
|
Additional Information
Head of Clinical Research Section
BIAL - Portela & Ca, SA
Phone: 351 22 986 6100
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER