Trial Outcomes & Findings for Efficacy and Safety of Eslicarbazepine Acetate as Therapy in Subjects With Fibromyalgia (NCT NCT01820585)

NCT ID: NCT01820585

Last Updated: 2013-07-19

Results Overview

The primary efficacy variable was the absolute change from baseline to endpoint in mean pain. Pain intensity was assessed on an 11-point (0-10) Numeric pain rating scale (NPRS), where 0 = no pain and 10 = worst possible pain and was recorded in a subject's diary. The subject was instructed to complete the assessment daily on awakening.Primary analyses were conducted on the full analysis set (FAS) which consisted of all randomised subjects who received at least 1 dose of study medication and with at least 1 post-randomisation rating of 24-h-average pain. The primary efficacy variable was the absolute change from baseline to endpoint in mean pain recorded in a subject's diary upon awakening each morning. An ANCOVA on the FAS revealed no statistically significant differences between the 3 ESL groups and the placebo group after 13 weeks of treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

528 participants

Primary outcome timeframe

Baseline and 13 Weeks

Results posted on

2013-07-19

Participant Flow

Subjects were screened in 84 centres in 16 European countries (Austria, Bulgaria, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Ukraine and United Kingdom). Study initiation date: 21 Apr 2009 Study completion date: 03 Sep 2010;

After completing procedures at V1, subjects returned to the study centre for V2. At V2, subjects, who had completed at least 4 subject diary pain assessments satisfactorily within the past 7 days, had an average pain score that was ≥4 and ≤9 and continued to meet all study entry criteria, were randomly assigned to 1 of the 4 treatment groups.

Participant milestones

Participant milestones
Measure	Placebo Placebo tablets matching the 400-mg and 600-mg tablets were administered Once daily (QD) by oral route.	ESL 400 mg Eslicarbazepine acetate (ESL) 400 mg : ESL was supplied in 400-mg tablets and was administered QD by oral route.	ESL 800 mg ESL 800 mg : ESL was supplied in 400-mg tablets and was administered QD by oral route	ESL 1200 mg ESL was supplied in 400-mg and 600-mg tablets and was administered QD by oral route.
Overall Study STARTED	131	130	135	132
Overall Study Randomized and Treated	131	130	135	132
Overall Study Full Analysis Set	131	130	135	129
Overall Study Completed Titration Period	128	125	131	126
Overall Study Entered Maintenance Period	128	124	131	123
Overall Study Completed Maintenance Period	105	98	101	84
Overall Study COMPLETED	104	98	101	83
Overall Study NOT COMPLETED	27	32	34	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo tablets matching the 400-mg and 600-mg tablets were administered Once daily (QD) by oral route.	ESL 400 mg Eslicarbazepine acetate (ESL) 400 mg : ESL was supplied in 400-mg tablets and was administered QD by oral route.	ESL 800 mg ESL 800 mg : ESL was supplied in 400-mg tablets and was administered QD by oral route	ESL 1200 mg ESL was supplied in 400-mg and 600-mg tablets and was administered QD by oral route.
Overall Study Adverse Event	9	13	23	34
Overall Study Lack of Efficacy	9	7	5	1
Overall Study Withdrawal by Subject	3	7	3	8
Overall Study Lost to Follow-up	3	3	0	3
Overall Study Protocol Violation	3	1	1	1
Overall Study Subject non-compliance	0	0	1	2
Overall Study at sponsor request	0	0	1	0
Overall Study Pregnancy	0	1	0	0

Baseline Characteristics

Efficacy and Safety of Eslicarbazepine Acetate as Therapy in Subjects With Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=131 Participants Tablets Placebo : Tablets	ESL 400 mg n=130 Participants Eslicarbazepine acetate (BIA 2-093) tablets ESL 400 mg : Eslicarbazepine acetate (BIA 2-093) tablets	ESL 800 mg n=135 Participants Eslicarbazepine acetate (BIA 2-093) tablets ESL 800 mg : Eslicarbazepine acetate (BIA 2-093) tablets	ESL 1200 mg n=132 Participants Eslicarbazepine acetate (BIA 2-093) tablets ESL 1200 mg : Eslicarbazepine acetate (BIA 2-093) tablets	Total n=528 Participants Total of all reporting groups
Sex: Female, Male Male	7 Participants n=5 Participants	16 Participants n=7 Participants	8 Participants n=5 Participants	10 Participants n=4 Participants	41 Participants n=21 Participants
Age, Customized <=65 Years	126 participants n=5 Participants	126 participants n=7 Participants	132 participants n=5 Participants	127 participants n=4 Participants	511 participants n=21 Participants
Age, Customized >65 years	5 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	5 participants n=4 Participants	17 participants n=21 Participants
Sex: Female, Male Female	124 Participants n=5 Participants	114 Participants n=7 Participants	127 Participants n=5 Participants	122 Participants n=4 Participants	487 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and 13 Weeks

Outcome measures

Outcome measures
Measure	Placebo n=130 Participants Tablets Placebo : Tablets	ESL 400 mg n=130 Participants Eslicarbazepine acetate (BIA 2-093) tablets ESL 400 mg : Eslicarbazepine acetate (BIA 2-093) tablets	ESL 800 mg n=135 Participants Eslicarbazepine acetate (BIA 2-093) tablets ESL 800 mg : Eslicarbazepine acetate (BIA 2-093) tablets	ESL 1200 mg n=129 Participants Eslicarbazepine acetate (BIA 2-093) tablets ESL 1200 mg : Eslicarbazepine acetate (BIA 2-093) tablets
Absolute Change From Baseline to Endpoint in Mean Pain	-1.0 units on a scale Standard Error 0.1735	-0.8 units on a scale Standard Error 0.1731	-1.2 units on a scale Standard Error 0.1704	-0.8 units on a scale Standard Error 0.1734

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 75 other events

Deaths: 0 deaths

ESL 400 mg

Serious events: 5 serious events

Other events: 86 other events

Deaths: 0 deaths

ESL 800 mg

Serious events: 6 serious events

Other events: 92 other events

Deaths: 0 deaths

ESL 1200 mg

Serious events: 1 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Research Section

Bial - Portela & Cª, S.A.

Phone: + 351 22 986 61 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=131 participants at risk Tablets Placebo : Tablets	ESL 400 mg n=130 participants at risk Eslicarbazepine acetate (BIA 2-093) tablets ESL 400 mg : Eslicarbazepine acetate (BIA 2-093) tablets	ESL 800 mg n=135 participants at risk Eslicarbazepine acetate (BIA 2-093) tablets ESL 800 mg : Eslicarbazepine acetate (BIA 2-093) tablets	ESL 1200 mg n=132 participants at risk Eslicarbazepine acetate (BIA 2-093) tablets ESL 1200 mg : Eslicarbazepine acetate (BIA 2-093) tablets
Gastrointestinal disorders Abdominal pain	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.77% 1/130 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Surgical and medical procedures Abortion induced	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.77% 1/130 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.74% 1/135 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Investigations Blood creatine phosphokinase increased	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.77% 1/130 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.74% 1/135 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Psychiatric disorders Completed suicide	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.74% 1/135 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Injury, poisoning and procedural complications Fall	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.76% 1/132 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Infections and infestations Gastroenteritis	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.77% 1/130 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.74% 1/135 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Gastrointestinal disorders Inguinal hernia	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.77% 1/130 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.74% 1/135 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Nervous system disorders Syncope	0.00% 0/131 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.74% 1/135 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Injury, poisoning and procedural complications Incisional hernia	0.76% 1/131 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Injury, poisoning and procedural complications Multiple injuries	0.76% 1/131 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)
Psychiatric disorders Suicidal ideation	0.76% 1/131 • Number of events 1 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/130 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/135 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)	0.00% 0/132 • Adverse events (AEs) were evaluated throughout the study that consisted of a 2-week Baseline Period, a 1-week Titration Period (active treatment or placebo) and a 12- week Maintenance Period (active treatment or placebo). Safety was evaluated based on adverse events (AEs)