Trial Outcomes & Findings for Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) in Acute Manic Episodes Associated With Bipolar I Disorder (NCT NCT01824602)
NCT ID: NCT01824602
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.
TERMINATED
PHASE2
38 participants
baseline and 3-week
2014-03-27
Participant Flow
STUDY DATES: From: 28 Feb 2006 To: 13 Nov 2006 Study centers: 25 study centers in Europe, South Africa and South America: 7 centers in Croatia, 6 centers in Spain, 6 centers in Argentina, 1 center in Chile and 5 centers in South Africa.
Patients who met the selection criteria at randomisation visit (V) (V2, Day 1) were randomised to 1 of 4 treatment groups: 600, 1200, or 1800 mg eslicarbazepine acetate, or placebo. Patients started the assigned treatment on Day 1 and were followed for up to 3 weeks.
Participant milestones
| Measure |
Group 4: Placebo
Placebo pills
Placebo : Placebo sugar pills
|
Group 3: Eslicarbazepine Acetate 600 mg
Eslicarbazepine acetate 600 mg
Eslicarbazepine acetate 600 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
Group 2: Eslicarbazepine Acetate 1200 mg
Eslicarbazepine acetate 1200 mg
Eslicarbazepine acetate 1200 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
Group 1: Eslicarbazepine Acetate 1800 mg
Eslicarbazepine acetate 1800 mg
Eslicarbazepine acetate 1800 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
11
|
8
|
9
|
10
|
|
Overall Study
Safety Population
|
11
|
8
|
9
|
10
|
|
Overall Study
Intent-to-treat Population
|
11
|
8
|
9
|
9
|
|
Overall Study
COMPLETED
|
10
|
8
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
4
|
5
|
Reasons for withdrawal
| Measure |
Group 4: Placebo
Placebo pills
Placebo : Placebo sugar pills
|
Group 3: Eslicarbazepine Acetate 600 mg
Eslicarbazepine acetate 600 mg
Eslicarbazepine acetate 600 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
Group 2: Eslicarbazepine Acetate 1200 mg
Eslicarbazepine acetate 1200 mg
Eslicarbazepine acetate 1200 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
Group 1: Eslicarbazepine Acetate 1800 mg
Eslicarbazepine acetate 1800 mg
Eslicarbazepine acetate 1800 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
2
|
|
Overall Study
Patient non-compliance
|
0
|
0
|
1
|
0
|
|
Overall Study
Adverse Event
|
1
|
0
|
2
|
2
|
|
Overall Study
Treatment failure
|
0
|
0
|
0
|
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 |
Group 4: Placebo
n=11 Participants
Placebo pills
Placebo : Placebo sugar pills
|
Group 3: Eslicarbazepine Acetate 600 mg
n=8 Participants
Eslicarbazepine acetate 600 mg
Eslicarbazepine acetate 600 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
Group 2: Eslicarbazepine Acetate 1200 mg
n=9 Participants
Eslicarbazepine acetate 1200 mg
Eslicarbazepine acetate 1200 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
Group 1: Eslicarbazepine Acetate 1800 mg
n=10 Participants
Eslicarbazepine acetate 1800 mg
Eslicarbazepine acetate 1800 mg : Eslicarbazepine acetate to be taken orally, was available as 600 mg tablets.
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
<=18 years
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
0 participants
n=483 Participants
|
0 participants
n=36 Participants
|
|
Age, Customized
Between 18 and 65 years
|
11 participants
n=93 Participants
|
8 participants
n=4 Participants
|
9 participants
n=27 Participants
|
9 participants
n=483 Participants
|
37 participants
n=36 Participants
|
|
Age, Customized
>=65 years
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
1 participants
n=483 Participants
|
1 participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
22 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
16 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: baseline and 3-weekPopulation: The ITT efficacy population of 37 patients 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 |
Placebo
n=11 Participants
ITT Population
|
ESL 600 mg
n=8 Participants
ITT Population
|
ESL 1200 mg
n=9 Participants
ITT Population
|
ESL 1800 mg
n=9 Participants
(ITT Population
|
|---|---|---|---|---|
|
Change in Young Mania Rating Scale (YMRS) Total Score From Baseline Until the End of the 3-week Treatment Period
|
-17.7 units on a scale
Standard Error 7.34
|
-16.9 units on a scale
Standard Error 2.75
|
-16.7 units on a scale
Standard Error 9.11
|
-11.3 units on a scale
Standard Error 10.89
|
Adverse Events
Placebo
ESL 600 mg
ESL 1200 mg
ESL 1800 mg
Serious adverse events
| Measure |
Placebo
n=11 participants at risk
Safety Population
|
ESL 600 mg
n=8 participants at risk
Safety Population
|
ESL 1200 mg
n=9 participants at risk
Safety Population
|
ESL 1800 mg
n=10 participants at risk
Safety Population
|
|---|---|---|---|---|
|
Psychiatric disorders
Mania
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
Other adverse events
| Measure |
Placebo
n=11 participants at risk
Safety Population
|
ESL 600 mg
n=8 participants at risk
Safety Population
|
ESL 1200 mg
n=9 participants at risk
Safety Population
|
ESL 1800 mg
n=10 participants at risk
Safety Population
|
|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/11 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Cardiac disorders
Tachycardia
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Eye disorders
Dry eye
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Eye disorders
Vision blurred
|
0.00%
0/11 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/11 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
30.0%
3/10 • Number of events 3 • 3 weeks
|
|
Gastrointestinal disorders
Paraesthesia oral
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
20.0%
2/10 • Number of events 2 • 3 weeks
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
22.2%
2/9 • Number of events 2 • 3 weeks
|
20.0%
2/10 • Number of events 2 • 3 weeks
|
|
General disorders
Chest pain
|
0.00%
0/11 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
General disorders
Fatigue
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
General disorders
Gait disturbance
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
General disorders
Malaise
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
General disorders
Pyrexia
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Infections and infestations
Bronchitis
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Infections and infestations
Bronchitis acute
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
Infections and infestations
Influenza
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
Infections and infestations
Nasopharyngitis
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/11 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
22.2%
2/9 • Number of events 2 • 3 weeks
|
40.0%
4/10 • Number of events 4 • 3 weeks
|
|
Nervous system disorders
Headache
|
27.3%
3/11 • Number of events 3 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
55.6%
5/9 • Number of events 5 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
Nervous system disorders
Lethargy
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/11 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Nervous system disorders
Somnolence
|
0.00%
0/11 • 3 weeks
|
12.5%
1/8 • Number of events 1 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
30.0%
3/10 • Number of events 3 • 3 weeks
|
|
Nervous system disorders
Syncope
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
Psychiatric disorders
Depression
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Psychiatric disorders
Mania
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
10.0%
1/10 • Number of events 1 • 3 weeks
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
9.1%
1/11 • Number of events 1 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
0.00%
0/9 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/11 • 3 weeks
|
0.00%
0/8 • 3 weeks
|
11.1%
1/9 • Number of events 1 • 3 weeks
|
0.00%
0/10 • 3 weeks
|
Additional Information
Head of Clinical Research Section
BIAL - Portela & Ca, SA
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER