Trial Outcomes & Findings for Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures (NCT NCT00988429)
NCT ID: NCT00988429
Last Updated: 2021-05-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
653 participants
Primary outcome timeframe
12-week maintenance period (Week 3 to week 14)
Results posted on
2021-05-19
Participant Flow
A total of 173 investigational sites in 19 countries (North America, 89 sites; Rest-of-World \[ROW\], 84 sites) screened and enrolled subjects. Of these, 160 sites randomized subjects into the study. Studied period (years): * First subject first visit: 02 December 2008 * Last subject last visit: 12 January 2012 (Part I)
The first period was an 8-week observation baseline period (Week -8 to Week -1) during which subjects were instructed on how to complete the seizure diary. At the end of the 8 week observational baseline period, eligible subjects were randomized in a 1:1:1 allocation ratio to 1 of 3 treatment groups (with a blinded treatment assignment)
Participant milestones
| Measure |
Placebo
Matching placebo tablets QD orally
|
800 mg QD
The study drug was a conventional immediate-release tablet of eslicarbazepine (ESL) and provided as either 400 mg or 800 mg dosage strengths (the 800 mg tablets were not used in North America). The composition was directly proportional between the strengths. The excipients used were standard pharmaceutical excipients of compendial grade, widely used in the pharmaceutical industry. The medication was taken orally.
|
1200 mg QD
The study drug was a conventional immediate-release tablet of eslicarbazepine (ESL) and provided as either 400 mg or 800 mg dosage strengths (the 800 mg tablets were not used in North America). The composition was directly proportional between the strengths. The excipients used were standard pharmaceutical excipients of compendial grade, widely used in the pharmaceutical industry. The medication was taken orally.
|
|---|---|---|---|
|
Overall Study
STARTED
|
226
|
216
|
211
|
|
Overall Study
Safety Population
|
224
|
216
|
210
|
|
Overall Study
Intention-to-treat (ITT) Population
|
220
|
215
|
205
|
|
Overall Study
COMPLETED
|
189
|
173
|
142
|
|
Overall Study
NOT COMPLETED
|
37
|
43
|
69
|
Reasons for withdrawal
| Measure |
Placebo
Matching placebo tablets QD orally
|
800 mg QD
The study drug was a conventional immediate-release tablet of eslicarbazepine (ESL) and provided as either 400 mg or 800 mg dosage strengths (the 800 mg tablets were not used in North America). The composition was directly proportional between the strengths. The excipients used were standard pharmaceutical excipients of compendial grade, widely used in the pharmaceutical industry. The medication was taken orally.
|
1200 mg QD
The study drug was a conventional immediate-release tablet of eslicarbazepine (ESL) and provided as either 400 mg or 800 mg dosage strengths (the 800 mg tablets were not used in North America). The composition was directly proportional between the strengths. The excipients used were standard pharmaceutical excipients of compendial grade, widely used in the pharmaceutical industry. The medication was taken orally.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
9
|
21
|
45
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
1
|
|
Overall Study
Non-Compliance with Study Drug
|
5
|
1
|
3
|
|
Overall Study
Physician Decision
|
1
|
0
|
3
|
|
Overall Study
Pregnancy
|
2
|
1
|
0
|
|
Overall Study
Protocol Violation
|
4
|
3
|
3
|
|
Overall Study
Withdrawal by Subject
|
7
|
7
|
12
|
|
Overall Study
Administrative Reasons
|
1
|
2
|
1
|
|
Overall Study
other reasons
|
8
|
8
|
1
|
Baseline Characteristics
Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures
Baseline characteristics by cohort
| Measure |
Placebo
n=224 Participants
Matching placebo tablets QD orally
|
800 mg QD
n=216 Participants
The study drug was a conventional immediate-release tablet of eslicarbazepine (ESL) and provided as either 400 mg or 800 mg dosage strengths (the 800 mg tablets were not used in North America). The composition was directly proportional between the strengths. The excipients used were standard pharmaceutical excipients of compendial grade, widely used in the pharmaceutical industry. The medication was taken orally.
|
1200 mg QD
n=210 Participants
The study drug was a conventional immediate-release tablet of eslicarbazepine (ESL) and provided as either 400 mg or 800 mg dosage strengths (the 800 mg tablets were not used in North America). The composition was directly proportional between the strengths. The excipients used were standard pharmaceutical excipients of compendial grade, widely used in the pharmaceutical industry. The medication was taken orally.
|
Total
n=650 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
218 Participants
n=5 Participants
|
211 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
631 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
112 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
324 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
112 Participants
n=5 Participants
|
109 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
326 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
46 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
126 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
142 Participants
n=5 Participants
|
137 Participants
n=7 Participants
|
134 Participants
n=5 Participants
|
413 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
28 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
87 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 12-week maintenance period (Week 3 to week 14)Population: Intent-to-treat (ITT) population was the primary population for the analysis of efficacy; ITT included all randomized subjects who received at least one dose of study treatment after randomization and had at least one post-baseline seizure frequency assessment.
Outcome measures
| Measure |
Placebo (ITT Population)
n=220 Participants
Matching placebo tablets QD orally
|
ESL 800 mg QD (ITT Population)
n=215 Participants
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
ESL 1200 mg QD (ITT Population)
n=205 Participants
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
|---|---|---|---|
|
Seizure Frequency Over the 12-week Maintenance Period.
|
7.88 Nº Standardized Seizures by 4 weeks
Standard Error 0.49 • Interval 6.98 to 8.9
|
6.54 Nº Standardized Seizures by 4 weeks
Standard Error 0.41 • Interval 5.77 to 7.4
|
6.00 Nº Standardized Seizures by 4 weeks
Standard Error 0.40 • Interval 5.26 to 6.84
|
SECONDARY outcome
Timeframe: Baseline (Week-8 through Week -1) and Maintenance period (Week 3 to week 14)Population: Intent-to-treat (ITT) population was the primary population for the analysis of efficacy; ITT included all randomized subjects who received at least one dose of study treatment after randomization and had at least one post-baseline seizure frequency assessment.
Subjects who had at least a 50% reduction from baseline in standardized seizure frequency during the maintenance period were classified as responders.
Outcome measures
| Measure |
Placebo (ITT Population)
n=220 Participants
Matching placebo tablets QD orally
|
ESL 800 mg QD (ITT Population)
n=215 Participants
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
ESL 1200 mg QD (ITT Population)
n=205 Participants
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
|---|---|---|---|
|
Proportion of Responders
|
23.1 percentage of participants
Interval 17.6 to 29.4
|
30.5 percentage of participants
Interval 24.2 to 37.4
|
42.6 percentage of participants
Interval 35.4 to 50.1
|
Adverse Events
Placebo (Safety Population)
Serious events: 7 serious events
Other events: 125 other events
Deaths: 0 deaths
ESL 800 mg QD (Safety Population)
Serious events: 14 serious events
Other events: 145 other events
Deaths: 0 deaths
ESL 1200 mg QD (Safety Population)
Serious events: 3 serious events
Other events: 163 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo (Safety Population)
n=224 participants at risk
Matching placebo tablets QD orally
|
ESL 800 mg QD (Safety Population)
n=216 participants at risk
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
ESL 1200 mg QD (Safety Population)
n=210 participants at risk
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal wall haematoma
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Infections and infestations
Malaria
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Contusion
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Head injury
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Therapeutic agent toxicity
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Investigations
Anticonvulsant drug level below therapeutic
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Cerebellar syndrome
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Encephalopathy
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Lumbar radiculopathy
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Partial seizures
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Partial seizures with secondary generalisation
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Simple partial seizures
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Status epilepticus
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Transient ischaemic attack
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Skin and subcutaneous tissue disorders
Leukocytoclastic vasculitis
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Vascular disorders
Aortic aneurysm
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Vascular disorders
Arterial haemorrhage
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
Other adverse events
| Measure |
Placebo (Safety Population)
n=224 participants at risk
Matching placebo tablets QD orally
|
ESL 800 mg QD (Safety Population)
n=216 participants at risk
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
ESL 1200 mg QD (Safety Population)
n=210 participants at risk
Oral tablets provided as either 400 mg or 800 mg dosage strengths
|
|---|---|---|---|
|
Nervous system disorders
Dizziness
|
8.5%
19/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
15.7%
34/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
26.2%
55/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Somnolence
|
5.4%
12/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
7.4%
16/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
17.1%
36/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Nausea
|
4.9%
11/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
7.4%
16/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
15.2%
32/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Headache
|
7.6%
17/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
9.3%
20/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
11.4%
24/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Vomiting
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.8%
6/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
11.0%
23/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Eye disorders
Diplopia
|
1.8%
4/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
6.5%
14/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
10.5%
22/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Ear and labyrinth disorders
Vertigo
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.8%
6/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
7.1%
15/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
General disorders
Fatigue
|
2.7%
6/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
3.7%
8/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
5.2%
11/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Endocrine disorders
Hypothyroidism
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Eye disorders
Vision blurred
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
4.6%
10/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
4.3%
9/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Eye disorders
Visual impairment
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.8%
4/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Constipation
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.8%
6/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Diarrhoea
|
2.2%
5/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Dyspepsia
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Gastrointestinal disorders
Toothache
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
General disorders
Asthenia
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
3.3%
7/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
General disorders
Gait disturbance
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
General disorders
Irritability
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
General disorders
Oedema peripheral
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
General disorders
Pyrexia
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Infections and infestations
Influenza
|
2.7%
6/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Infections and infestations
Nasopharyngitis
|
3.6%
8/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.8%
6/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Infections and infestations
Pharyngitis
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Infections and infestations
Upper respiratory tract infection
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Infections and infestations
Urinary tract infection
|
1.8%
4/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.8%
6/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Contusion
|
1.8%
4/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Head injury
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Injury, poisoning and procedural complications
Thermal burn
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Investigations
Blood creatine phosphokinase increased
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Investigations
Blood sodium decreased
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Investigations
Weight increased
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.3%
5/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
3.3%
7/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.8%
4/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.93%
2/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.3%
3/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
3.2%
7/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Bone metabolism disorder
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.2%
5/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Amnesia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Ataxia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
4.8%
10/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Balance disorder
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
3.2%
7/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
3.8%
8/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Cerebellar syndrome
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Coordination abnormal
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Disturbance in attention
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
3.8%
8/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Lethargy
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Memory impairment
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Migraine
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.9%
6/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Nystagmus
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.9%
6/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Partial seizures
|
3.1%
7/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.8%
6/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Partial seizures with secondary generalisation
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Nervous system disorders
Tremor
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
4.3%
9/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Psychiatric disorders
Anxiety
|
2.2%
5/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.8%
6/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.48%
1/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Psychiatric disorders
Depression
|
2.7%
6/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.3%
5/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
2.9%
6/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Psychiatric disorders
Insomnia
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.45%
1/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.00%
0/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.89%
2/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.4%
3/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Vascular disorders
Flushing
|
0.00%
0/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.95%
2/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
|
Vascular disorders
Hypertension
|
2.2%
5/224 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
0.46%
1/216 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
1.9%
4/210 • Adverse events (AEs) were monitored for the duration of the study, starting at V1
|
Additional Information
Head of Clinical Research
Bial - portela & Cª, S.A.
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