Bipolar I Disorder
Conditions
Keywords
bipolar I disorder, Eslicarbazepine acetate, BIA 2-093
Brief summary
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. Patients stable in remission continued double-blind therapy until approximately 6 months after the last patient entered Part II.
Detailed description
The occurrence of a new manic/depressive episode was considered a treatment failure, and the patient was discontinued from the study. At the end of Part II, 6 months after last patient enrolled and after no longer than approximately 15 months, if patients were still in remission and the investigational product was well-tolerated, patients had the option to enter long-term open-label treatment at the same dosage as used in Part II until a new episode occurred, until marketing was authorized, or until clinical development of BIA 2-093 in the recurrence prevention indication was discontinued. If patients did not enter long-term treatment, an established recurrence prevention medication was prescribed, and BIA 2-093 was tapered off (patients assigned to 1800 mg had the daily dose decreased to 900 mg for 6 days; those assigned to 900 mg or 300 mg received placebo for 6 days).
Interventions
DRUGBIA 2-093 1800 mg once daily [Group 1 (Part II)]
BIA 2-093 1800 mg taken orally in the evening, for 2 weeks
DRUGBIA 2-093 900 mg once daily [Group 2 (Part II)]
BIA 2-093 900 mg taken orally in the evening, for 2 weeks
DRUGBIA 2-093 300 mg once daily [Group 3 (Part II)]
BIA 2-093 300 mg taken orally in the evening, for 2 weeks.
DRUGBIA 2-093 900 mg (Part I)
In Part I, patients received one 900 mg BIA 2-093 tablet once daily, taken orally in the evening, for 2 weeks.
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* signed the Informed consent form (ICF) * completed the 3-week treatment period in Protocol with identification number SCO/BIA-2093-203 or Protocol with identification number PRA/BIA-2093-204 and shown response to treatment, defined as ≥ 50% improvement in the Young Mania Rating Scale (YMRS) total score or a YMRS total score \< 12 * presented a serum pregnancy test (in cases of women of childbearing potential) consistent with a non-gravid state and used double-barrier contraception throughout the study
Exclusion criteria
* relevant electrocardiogram (ECG) or laboratory abnormalities * any uncontrolled clinically relevant disorder * uninsured capability to comply with the study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population) | 6 months | 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. |
Participant flow
Recruitment details
This was a multicenter study. Approximately 60 centers in Europe, South America, and South Africa enrolled patients in this study.
Pre-assignment details
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
Participants by arm
| Arm | Count |
|---|---|
| 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. | 35 |
| 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. | 26 |
| 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. | 26 |
| ESL (Part I - Not Randomised Patients) This group corresponds to the 17 patients who did not complete part I and therefore where not randomised to any traeatment group. | 17 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| PART I | Patient non-compliance | 0 | 0 | 0 | 1 |
| PART I | reason unspecified | 0 | 0 | 0 | 3 |
| PART I | Treatment failure | 0 | 0 | 0 | 7 |
| PART I | Withdrawal by Subject | 0 | 0 | 0 | 6 |
| PART II | Adverse Event | 3 | 3 | 1 | 0 |
| PART II | Patient non-compliance | 5 | 2 | 4 | 0 |
| PART II | reason unspecified | 2 | 2 | 2 | 0 |
| PART II | Treatment failure | 6 | 4 | 5 | 0 |
| PART II | Withdrawal by Subject | 3 | 3 | 7 | 0 |
Baseline characteristics
| Characteristic | Group 3 [(Part II) 300 mg] | Group 2 [(Part II) 900 mg] | Group 1 [(Part II) 1800 mg] | ESL (Part I - Not Randomised Patients) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 24 Participants | 25 Participants | 17 Participants | 100 Participants |
| Sex: Female, Male Female | 16 Participants | 11 Participants | 11 Participants | 12 Participants | 50 Participants |
| Sex: Female, Male Male | 19 Participants | 15 Participants | 15 Participants | 5 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 35 | 6 / 26 | 4 / 26 |
| serious Total, serious adverse events | 2 / 35 | 4 / 26 | 2 / 26 |
Outcome results
Primary
Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population)
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.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIA 2-093 300 mg | Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population) | 26 participants |
| BIA 2-093 900 mg | Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population) | 14 participants |
| BIA 2-093 1800 mg | Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population) | 16 participants |