Bipolar I DisorderPhase 2NCT01822678

Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) in Acute Manic Episodes Associated With Bipolar I Disorder

A Phase 2 study testing Eslicarbazepine Acetate in people with Bipolar I Disorder, run by Bial - Portela C S.A..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Bipolar I Disorder
What is being tested?: Eslicarbazepine Acetate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 161 participants
Where: No sites listed yet
Study dates: Dec 2005to Nov 2006
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

aged ≥18 years;
a documented diagnosis of bipolar I disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria (i.e., 296.0, 296.4 or 296.6) [8];
currently displaying an acute manic (including mixed) episode according to the DSM-IV criteria;
a Young Mania Rating Scale (YMRS) total score of ≥20;
symptoms of the current manic episode starting within 2 weeks prior to randomisation (V2, Day 1);
able to undergo a standard evaluation, including clinical interview, ratings and laboratory studies;
signed informed consent form;
post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; women of childbearing potential had to present a serum pregnancy test consistent with a non-gravid state and had to use double-barrier contraception until the post-study visit (PSV).

Who cannot join

a history of schizophrenia or schizoaffective disorder, psychotic features or rapid cycling;
currently treated with carbamazepine or oxcarbazepine;
a history of unresponsiveness, intolerance or hypersensitivity to related compounds (carbamazepine, oxcarbazepine or licarbazepine);
use of any depot-neuroleptics for the current manic episode;
abuse of stimulating drugs or use of any systemic sympathicomimetic drug within the previous 2 weeks;
electroconvulsive therapy within the previous 3 months;

Show all 21Show fewer

a history of dependence or chronic abuse from alcohol, drugs or medications within the last year;
judged clinically to be at risk of harm to self or others;
second or third-degree atrioventricular blockade not corrected with a pacemaker;
relevant electrocardiogram (ECG) or laboratory abnormalities;
calculated creatinine clearance <30 mL/min [men: (140-age) x weight / serum creatinine x 72; women: (0.85) (140-age) x weight / serum creatinine x 72. Age in years, weight in kg, and serum creatinine in mg/dL];
pregnant or nursing;
participating in another drug clinical trial within the last 2 months before the randomisation visit;
not ensured capability to perform the trial or to comply with the study protocol (e.g., mental retardation or severe inability to communicate);
any other uncontrolled clinically relevant disorder;
previous treatment with Eslicarbazepine Acetate;
a history or presence of bone marrow impairment or depression (introduced by protocol amendment No. 1);
a history or presence of acute intermittent porphyria (introduced by protocol amendment No. 1).
Patients receiving treatment for bipolar disorder or other central nervous system disorders at randomisation were excluded from randomisation. If the patients had previously used such medications the following restrictions had to be taken into account:
Patients treated with bipolar disorder preventive medication (for carbamazepine or oxcarbazepine see exclusion criteria), antidepressants, antipsychotic, anxiolytic, antiparkinsonian, and/or other potentially centrally acting drugs had to be washed-out for at least 2 days prior to randomisation (V2, Day 1).
Patients treated with lithium or valproate could only be randomised with plasma levels < 0.5 mmol/L and < 50 mg/L, respectively.

About this study

Official title: Efficacy and Safety of Eslicarbazepine Acetate (BIA 2 093) in Acute Manic Episodes Associated With Bipolar I Disorder in a Double Blind, Randomised, Dose Titration, Placebo Controlled, Multicentre Clinical Trial

Multicentre, double-blind, randomised, parallel-group, placebo-controlled dose-titration study; depending on clinical efficacy, up-titration of dosage 3 and 6 days after start of treatment; maintenance of individual maximum dose for the rest of the total 3-week treatment period; subsequently, down-titration (according to the dose steps and the time intervals of up-titration) and administration of an established anti-manic therapy during the tapering-off period (in patients who discontinued treatment) or entry into a recurrence prevention study (Protocol PRA+SCO/BIA-2093-205; reported under separate cover) as an option for patients who responded to the study treatment

Read the detailed description

Objectives:

The primary objective was to evaluate the dose-dependent efficacy of 2 dose-titration regimens of Eslicarbazepine Acetate (ESL) compared with placebo as therapy in patients with acute mania.

The secondary objective was to evaluate the safety and tolerability of 2 dose-titration regimens of Eslicarbazepine Acetate in comparison to placebo.

Conditions: Bipolar I Disorder
Being tested: Eslicarbazepine Acetate, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Eslicarbazepine AcetateDrug
Also called Eslicarbazepine Acetate tablets
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 AcetateDrug
Also called Eslicarbazepine Acetate tablets
Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.
PlaceboDrug
Also called sugar pill
Placebo

Study groups in NCT01822678
Study group	Role	What they receive
Group 1	Experimental	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. Receives: Drug: Eslicarbazepine Acetate
Group 2	Experimental	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. Receives: Drug: Eslicarbazepine Acetate
Group 3	Placebo comparator	Group 3: Placebo (change in daily number of tablets administered, according to clinical response). Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in the Young Mania Rating Scale (YMRS) Total Score at the End of the 3-week Treatment Period, in Relation to the Baseline.
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.
Measured: baseline and 3-week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2005Nov 2006

First posted2 Apr 2013 (estimated)
Study startDec 2005
Primary completionNov 2006
Study completionNov 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Bipolar I DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 161 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01822678
Sponsor's protocol ID: BIA-2093-203
Status last verified: Feb 2014
First submitted: 28 Mar 2013
Last updated: 27 Mar 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety of Eslicarbazepine Acetate (BIA 2 093) in Acute Manic Episodes Associated With Bipolar I Disorder in a Double Blind, Randomised, Dose Titration, Placebo Controlled, Multicentre Clinical Trial
ClinicalTrials.gov ID: NCT01822678
Acronym / sponsor ID: BIA-2093-203
Conditions: Bipolar I Disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 161 participants (actual)
Lead sponsor: Bial - Portela C S.A.Industry (pharma, biotech, devices)
Study start: Dec 2005
Primary completion: Nov 2006 (actual)
Study completion: Nov 2006 (actual)
First posted: 2 Apr 2013 (estimated)
Results: Posted 2 Aug 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Objectives:

The primary objective was to evaluate the dose-dependent efficacy of 2 dose-titration regimens of Eslicarbazepine Acetate (ESL) compared with placebo as therapy in patients with acute mania.

The secondary objective was to evaluate the safety and tolerability of 2 dose-titration regimens of Eslicarbazepine Acetate in comparison to placebo.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Group 1	Experimental	Drug: Eslicarbazepine AcetateGroup 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.
Group 2	Experimental	Drug: Eslicarbazepine AcetateGroup 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.
Group 3	Placebo comparator	Drug: PlaceboGroup 3: Placebo (change in daily number of tablets administered, according to clinical response).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

aged ≥18 years;
a documented diagnosis of bipolar I disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria (i.e., 296.0, 296.4 or 296.6) [8];
currently displaying an acute manic (including mixed) episode according to the DSM-IV criteria;
a Young Mania Rating Scale (YMRS) total score of ≥20;
symptoms of the current manic episode starting within 2 weeks prior to randomisation (V2, Day 1);

Key exclusion criteria (21 listed)

a history of schizophrenia or schizoaffective disorder, psychotic features or rapid cycling;
currently treated with carbamazepine or oxcarbazepine;
a history of unresponsiveness, intolerance or hypersensitivity to related compounds (carbamazepine, oxcarbazepine or licarbazepine);
use of any depot-neuroleptics for the current manic episode;
abuse of stimulating drugs or use of any systemic sympathicomimetic drug within the previous 2 weeks;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Eslicarbazepine AcetateAlso: Eslicarbazepine Acetate tabletsEslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.	Drug	Group 1
Eslicarbazepine AcetateAlso: Eslicarbazepine Acetate tabletsEslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.	Drug	Group 2
PlaceboAlso: sugar pillPlacebo	Drug	Group 3

Primary outcome

Change in the Young Mania Rating Scale (YMRS) Total Score at the End of the 3-week Treatment Period, in Relation to the Baseline.
Time frame: baseline and 3-week
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.

Results and safety

Results posted to the registry on 2 Aug 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ESL 800 mg	57	45
ESL 600 mg	64	49
Placebo	40	29

Primary outcome: Change in the Young Mania Rating Scale (YMRS) Total Score at the End of the 3-week Treatment Period, in Relation to the Baseline.

Time frame: baseline and 3-week. Least squares mean (Standard Error). Unit: units on a scale

Measure	BIA 2-093 - 2400 mg (Maximum Dose) n = 57	BIA 2-093 - 1800 mg (Maximum Dose) n = 63	Placebo n = 40
Value	-14.2 (1.17)	-12.5 (1.12)	-10.3 (1.40)

Population analysed: 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).

Adverse events

Time frame: Up to 4 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BIA 2-093 - 2400 mg (Maximum Dose)	2 of 57 (3.5%)	20 of 57 (35.1%)	Not reported
BIA 2-093 - 1800 mg (Maximum Dose)	2 of 64 (3.1%)	25 of 64 (39.1%)	Not reported
Placebo	1 of 40 (2.5%)	10 of 40 (25%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Patrício Soares-da-Silva, MD, PhD study director

BIAL - Portela & Ca. SA

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Eslicarbazepine Acetate in people with Bipolar I Disorder, run by Bial - Portela C S.A..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the Young Mania Rating Scale (YMRS) Total Score at the End of the 3-week Treatment Period, in Relation to the Baseline. (time frame: baseline and 3-week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01822678.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2014; AzTrials last refreshed its copy on 8 Nov 2026.