Trial Outcomes & Findings for Efficacy, Safety, and Tolerability of Eslicarbazepine Acetate in the Recurrence Prevention of Bipolar I Disorder (NCT NCT01825837)

Last Updated: 2014-03-27

Results Overview

The CGI-BP scale is a modification of the CGI scale, which provides a means of assessing severity and treatment-related improvement in manic and depressive domains reflecting clinically relevant degrees of change. The concept of improvement refers to the clinical distance between the individual's current condition and that prior to the start of treatment. The scale for 'severity of illness' measures mania, depression and overall illness on a 7 point scale from 1 ('normal, not ill') to 7 ('very severely ill'). The scale for 'change from preceding phase' and 'change from worst phase' measures mania, depression, and overall illness on an 8-point scale from 1 (very much improved) to 8 ('not applicable'). If the patient, in 'change from preceding phase', at any visit during the double-blind, has a score of 5, 6, or 7 in any of 3 categories (mania, depression, or overall bipolar illness), then the illness will be considered to have worsened.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

6 months

Results posted on

2014-03-27

Participant Flow

This was a multicenter study. Approximately 60 centers in Europe, South America, and South Africa enrolled patients in this study.

This was an extension study consisting of 2 parts. In Part I, all participants received open-label treatment with BIA 2-093 900 mg once daily for 2 weeks. Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily

Participant milestones

Participant milestones
Measure	Group 3 [(Part II) 300 mg] BIA 2-093 300 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 2 [(Part II) 900 mg] BIA 2-093 900 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 1 [(Part II) 1800 mg] BIA 2-093 1800 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	ESL (Part I) In Part I, all participants received open-label treatment with BIA 2-093 900 mg once daily for 2 weeks. The participants that completed part I were randomised in Part II.
PART I STARTED	0	0	0	104
PART I Enrolled	0	0	0	104
PART I Safety Population (Open-Label)	0	0	0	104
PART I COMPLETED	0	0	0	87
PART I NOT COMPLETED	0	0	0	17
PART II STARTED	35	26	26	0
PART II Randomized Patients	35	26	26	0
PART II Safety Population (Double-Blind)	35	26	26	0
PART II Intent-to-Treat Population	34	25	26	0
PART II Per-Protocol Population	32	23	24	0
PART II COMPLETED	16	12	7	0
PART II NOT COMPLETED	19	14	19	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 3 [(Part II) 300 mg] BIA 2-093 300 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 2 [(Part II) 900 mg] BIA 2-093 900 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 1 [(Part II) 1800 mg] BIA 2-093 1800 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	ESL (Part I) In Part I, all participants received open-label treatment with BIA 2-093 900 mg once daily for 2 weeks. The participants that completed part I were randomised in Part II.
PART I Withdrawal by Subject	0	0	0	6
PART I Patient non-compliance	0	0	0	1
PART I Treatment failure	0	0	0	7
PART I reason unspecified	0	0	0	3
PART II Withdrawal by Subject	3	3	7	0
PART II Patient non-compliance	5	2	4	0
PART II Adverse Event	3	3	1	0
PART II Treatment failure	6	4	5	0
PART II reason unspecified	2	2	2	0

Baseline Characteristics

Efficacy, Safety, and Tolerability of Eslicarbazepine Acetate in the Recurrence Prevention of Bipolar I Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 3 [(Part II) 300 mg] n=35 Participants BIA 2-093 300 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 2 [(Part II) 900 mg] n=26 Participants BIA 2-093 900 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 1 [(Part II) 1800 mg] n=26 Participants BIA 2-093 1800 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	ESL (Part I - Not Randomised Patients) n=17 Participants This group corresponds to the 17 patients who did not complete part I and therefore where not randomised to any traeatment group.	Total n=104 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants	24 Participants n=7 Participants	25 Participants n=5 Participants	17 Participants n=4 Participants	100 Participants n=21 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	50 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	5 Participants n=4 Participants	54 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	BIA 2-093 300 mg n=34 Participants PART II - Intent-to-Treat Population	BIA 2-093 900 mg n=25 Participants PART II - Intent-to-Treat Population	BIA 2-093 1800 mg n=26 Participants PART II - Intent-to-Treat Population
Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population)	26 participants	14 participants	16 participants

Adverse Events

Group 3 [(Part II) 300 mg]

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Group 2 [(Part II) 900 mg]

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Group 1 [(Part II) 1800 mg]

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group 3 [(Part II) 300 mg] n=35 participants at risk BIA 2-093 300 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 2 [(Part II) 900 mg] n=26 participants at risk BIA 2-093 900 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.	Group 1 [(Part II) 1800 mg] n=26 participants at risk BIA 2-093 1800 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening.
Blood and lymphatic system disorders Anemia	0.00% 0/35 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	3.8% 1/26 • Number of events 1 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	0.00% 0/26 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/35 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	3.8% 1/26 • Number of events 1 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	0.00% 0/26 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.
General disorders Disease progression	0.00% 0/35 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	3.8% 1/26 • Number of events 1 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	3.8% 1/26 • Number of events 1 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.
Infections and infestations Bronchitis	0.00% 0/35 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	0.00% 0/26 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	3.8% 1/26 • Number of events 1 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.
Infections and infestations Pneumonia	0.00% 0/35 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	3.8% 1/26 • Number of events 1 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	0.00% 0/26 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.
Psychiatric disorders Depression	0.00% 0/35 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	3.8% 1/26 • Number of events 1 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	0.00% 0/26 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.
Psychiatric disorders Mania	5.7% 2/35 • Number of events 2 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	0.00% 0/26 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.	0.00% 0/26 • Double-blind period (Part II first administration date until study termination) 6 months Part II Double-Blind Period (Safety Population): safety population included all patients who received at least 1 dose of investigational product after randomization. Please note that adverse events that occurred in Parts I and II were summarized separately.

Other adverse events

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