Trial Outcomes & Findings for Pharmacokinetics, Efficacy and Tolerability of BIA 2-093 (NCT NCT02170064)
NCT ID: NCT02170064
Last Updated: 2017-09-20
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
pre-dose, and ½, 1½, 3, 4½, 6 and 12 hours post-dose
Results posted on
2017-09-20
Participant Flow
Participant milestones
| Measure |
Group 1 (2-6 Yrs)
At the end of the baseline phase, patients meeting the final selection criteria were admitted to three consecutive 4-week treatment periods in which they received Eslicarbazepine acetate once-daily at the following dosage regimens: 5 mg/kg/day in the first 4 weeks, 15 mg/kg/day in weeks 5-8 and 30 mg/kg/day or 1800 mg/day, whichever less, in weeks 9-12. After the last treatment period, dose was down-titrated during a 2-week period or patient continued receiving Eslicarbazepine acetate ("compassionate use") if both parent(s)/guardian(s)/patient and his/her physician agreed this was in the best patient's interest.
For Group 1 (2-6 years), oral suspension 50 mg/mL was used. The dose was to be rounded to the nearest 25 mg unit.
|
Group 2 (7-11 Years)
At the end of the baseline phase, patients meeting the final selection criteria were admitted to three consecutive 4-week treatment periods in which they received Eslicarbazepine acetate once-daily at the following dosage regimens: 5 mg/kg/day in the first 4 weeks, 15 mg/kg/day in weeks 5-8 and 30 mg/kg/day or 1800 mg/day, whichever less, in weeks 9-12. After the last treatment period, dose was down-titrated during a 2-week period or patient continued receiving Eslicarbazepine acetate ("compassionate use") if both parent(s)/guardian(s)/patient and his/her physician agreed this was in the best patient's interest.
For Group 2 (7-11 years) and Group 3 (12-17 years), Eslicarbazepine acetate strengths 200 mg, 400 mg, 600 mg and 800 mg tablets might be used. The dose was to be rounded to the nearest 100 mg unit. Half tablets might be used for dosage adjustment (tablets were scored).
|
Group 3 (12-17 Years)
At the end of the baseline phase, patients meeting the final selection criteria were admitted to three consecutive 4-week treatment periods in which they received Eslicarbazepine acetate once-daily at the following dosage regimens: 5 mg/kg/day in the first 4 weeks, 15 mg/kg/day in weeks 5-8 and 30 mg/kg/day or 1800 mg/day, whichever less, in weeks 9-12. After the last treatment period, dose was down-titrated during a 2-week period or patient continued receiving Eslicarbazepine acetate ("compassionate use") if both parent(s)/guardian(s)/patient and his/her physician agreed this was in the best patient's interest.
For Group 2 (7-11 years) and Group 3 (12-17 years), Eslicarbazepine acetate strengths 200 mg, 400 mg, 600 mg and 800 mg tablets might be used. The dose was to be rounded to the nearest 100 mg unit. Half tablets might be used for dosage adjustment (tablets were scored).
|
|---|---|---|---|
|
Overall Study
STARTED
|
15
|
9
|
11
|
|
Overall Study
Safety Population (SP)
|
12
|
8
|
11
|
|
Overall Study
Pharmacokinetic Population (PKP)
|
11
|
8
|
10
|
|
Overall Study
Efficacy Population (EP)
|
11
|
8
|
10
|
|
Overall Study
COMPLETED
|
9
|
7
|
10
|
|
Overall Study
NOT COMPLETED
|
6
|
2
|
1
|
Reasons for withdrawal
| Measure |
Group 1 (2-6 Yrs)
At the end of the baseline phase, patients meeting the final selection criteria were admitted to three consecutive 4-week treatment periods in which they received Eslicarbazepine acetate once-daily at the following dosage regimens: 5 mg/kg/day in the first 4 weeks, 15 mg/kg/day in weeks 5-8 and 30 mg/kg/day or 1800 mg/day, whichever less, in weeks 9-12. After the last treatment period, dose was down-titrated during a 2-week period or patient continued receiving Eslicarbazepine acetate ("compassionate use") if both parent(s)/guardian(s)/patient and his/her physician agreed this was in the best patient's interest.
For Group 1 (2-6 years), oral suspension 50 mg/mL was used. The dose was to be rounded to the nearest 25 mg unit.
|
Group 2 (7-11 Years)
At the end of the baseline phase, patients meeting the final selection criteria were admitted to three consecutive 4-week treatment periods in which they received Eslicarbazepine acetate once-daily at the following dosage regimens: 5 mg/kg/day in the first 4 weeks, 15 mg/kg/day in weeks 5-8 and 30 mg/kg/day or 1800 mg/day, whichever less, in weeks 9-12. After the last treatment period, dose was down-titrated during a 2-week period or patient continued receiving Eslicarbazepine acetate ("compassionate use") if both parent(s)/guardian(s)/patient and his/her physician agreed this was in the best patient's interest.
For Group 2 (7-11 years) and Group 3 (12-17 years), Eslicarbazepine acetate strengths 200 mg, 400 mg, 600 mg and 800 mg tablets might be used. The dose was to be rounded to the nearest 100 mg unit. Half tablets might be used for dosage adjustment (tablets were scored).
|
Group 3 (12-17 Years)
At the end of the baseline phase, patients meeting the final selection criteria were admitted to three consecutive 4-week treatment periods in which they received Eslicarbazepine acetate once-daily at the following dosage regimens: 5 mg/kg/day in the first 4 weeks, 15 mg/kg/day in weeks 5-8 and 30 mg/kg/day or 1800 mg/day, whichever less, in weeks 9-12. After the last treatment period, dose was down-titrated during a 2-week period or patient continued receiving Eslicarbazepine acetate ("compassionate use") if both parent(s)/guardian(s)/patient and his/her physician agreed this was in the best patient's interest.
For Group 2 (7-11 years) and Group 3 (12-17 years), Eslicarbazepine acetate strengths 200 mg, 400 mg, 600 mg and 800 mg tablets might be used. The dose was to be rounded to the nearest 100 mg unit. Half tablets might be used for dosage adjustment (tablets were scored).
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
1
|
1
|
|
Overall Study
Physician Decision
|
1
|
1
|
0
|
Baseline Characteristics
Pharmacokinetics, Efficacy and Tolerability of BIA 2-093
Baseline characteristics by cohort
| Measure |
Group 1 (2-6 Yrs)
n=11 Participants
Efficacy population (EP)
|
Group 2 (7-11 Yrs)
n=8 Participants
Efficacy population (EP)
|
Group 3 (12-17 Yrs)
n=10 Participants
Efficacy population (EP)
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
4.1 years
STANDARD_DEVIATION 1.38 • n=5 Participants
|
9.1 years
STANDARD_DEVIATION 1.55 • n=7 Participants
|
14.5 years
STANDARD_DEVIATION 1.58 • n=5 Participants
|
9.1 years
STANDARD_DEVIATION 4.73 • n=4 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: pre-dose, and ½, 1½, 3, 4½, 6 and 12 hours post-doseOutcome measures
| Measure |
Group 1 (2-6 Yrs)
n=11 Participants
Efficacy population (EP)
|
Group 2 (7-11 Yrs)
n=8 Participants
Efficacy population (EP)
|
Group 3 (12-17 Yrs)
n=10 Participants
Efficacy population (EP)
|
|---|---|---|---|
|
Maximum Observed Plasma Drug Concentration (Cmax) Post-dose
Dosage regimen 5 mg/kg/day
|
6921 ng/mL
Standard Deviation 1794
|
4820 ng/mL
Standard Deviation 1693
|
6382 ng/mL
Standard Deviation 1854
|
|
Maximum Observed Plasma Drug Concentration (Cmax) Post-dose
Dosage regimen 15 mg/kg/day
|
16183 ng/mL
Standard Deviation 2609
|
16395 ng/mL
Standard Deviation 3680
|
17194 ng/mL
Standard Deviation 3410
|
|
Maximum Observed Plasma Drug Concentration (Cmax) Post-dose
Dosage regimen 30 mg/kg/day
|
29935 ng/mL
Standard Deviation 4627
|
26890 ng/mL
Standard Deviation 6944
|
32400 ng/mL
Standard Deviation 6005
|
PRIMARY outcome
Timeframe: pre-dose, and ½, 1½, 3, 4½, 6 and 12 hours post-doseOutcome measures
| Measure |
Group 1 (2-6 Yrs)
n=11 Participants
Efficacy population (EP)
|
Group 2 (7-11 Yrs)
n=8 Participants
Efficacy population (EP)
|
Group 3 (12-17 Yrs)
n=10 Participants
Efficacy population (EP)
|
|---|---|---|---|
|
Time of Occurrence of Cmax (Tmax).
Dosage regimen 5 mg/kg/day
|
1 hours
Standard Deviation 1
|
2 hours
Standard Deviation 1
|
2 hours
Standard Deviation 1
|
|
Time of Occurrence of Cmax (Tmax).
Dosage regimen 15 mg/kg/day
|
2 hours
Standard Deviation 1
|
3 hours
Standard Deviation 1
|
2 hours
Standard Deviation 1
|
|
Time of Occurrence of Cmax (Tmax).
Dosage regimen 30 mg/kg/day
|
1 hours
Standard Deviation 0
|
3 hours
Standard Deviation 1
|
3 hours
Standard Deviation 2
|
SECONDARY outcome
Timeframe: Baseline, end of 5 mg/kg/day treatment period (4 weeks), 15 mg/kg/day treatment period (4 weeks) and 30 mg/kg/day treatment period (4 weeks).The efficacy variables were the percentage change in seizure frequency during each 4-week treatment period compared to the baseline phase. Seizures were recorded in the patient's diary during the baseline phase and during the following 4-week treatment periods. Seizure frequency for each patient was standardised to a frequency per 28 days period (i.e., mean daily frequency multiplied by 28). Changes in seizure frequency were analysed for each age group separately.
Outcome measures
| Measure |
Group 1 (2-6 Yrs)
n=11 Participants
Efficacy population (EP)
|
Group 2 (7-11 Yrs)
n=8 Participants
Efficacy population (EP)
|
Group 3 (12-17 Yrs)
n=10 Participants
Efficacy population (EP)
|
|---|---|---|---|
|
Percentage Change in Seizure Frequency During Each 4-week Treatment Period Compared to the Baseline Phase
5Dosage regimen 5 mg/kg/day
|
-28.2 percent change
Interval -60.0 to 13.0
|
-11.7 percent change
Interval -20.0 to 278.2
|
-17.1 percent change
Interval -56.0 to 30.0
|
|
Percentage Change in Seizure Frequency During Each 4-week Treatment Period Compared to the Baseline Phase
Dosage regimen 15 mg/kg/day
|
-24.8 percent change
Interval -93.0 to -6.0
|
5.0 percent change
Interval -55.6 to 344.6
|
-31.7 percent change
Interval -71.0 to 19.0
|
|
Percentage Change in Seizure Frequency During Each 4-week Treatment Period Compared to the Baseline Phase
Dosage regimen 30 mg/kg/day
|
-40.6 percent change
Interval -86.0 to -4.0
|
12.2 percent change
Interval -100.0 to 166.7
|
-43.1 percent change
Interval -77.0 to 21.0
|
Adverse Events
Group 1 (2-6 Yrs)
Serious events: 2 serious events
Other events: 9 other events
Deaths: 0 deaths
Group 2 (7-11 Yrs)
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Group 3 (12-17 Yrs)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1 (2-6 Yrs)
n=12 participants at risk
Safety population (SP)
|
Group 2 (7-11 Yrs)
n=8 participants at risk
Safety population (SP)
|
Group 3 (12-17 Yrs)
n=11 participants at risk
Safety population (SP)
|
|---|---|---|---|
|
Nervous system disorders
Seizures
|
8.3%
1/12
|
12.5%
1/8
|
0.00%
0/11
|
|
Infections and infestations
Bronchopneumonia
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
Other adverse events
| Measure |
Group 1 (2-6 Yrs)
n=12 participants at risk
Safety population (SP)
|
Group 2 (7-11 Yrs)
n=8 participants at risk
Safety population (SP)
|
Group 3 (12-17 Yrs)
n=11 participants at risk
Safety population (SP)
|
|---|---|---|---|
|
Gastrointestinal disorders
Stomatitis
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
|
General disorders
Flu like symptoms
|
0.00%
0/12
|
0.00%
0/8
|
9.1%
1/11
|
|
Infections and infestations
Upper respiratory tract infection
|
41.7%
5/12
|
37.5%
3/8
|
0.00%
0/11
|
|
Nervous system disorders
Incoordination
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
|
Nervous system disorders
Psychomotor agitation
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/11
|
|
Nervous system disorders
Somnolence
|
0.00%
0/12
|
37.5%
3/8
|
45.5%
5/11
|
|
Psychiatric disorders
Aggressive behaviour
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/11
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial pneumonia
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
|
Eye disorders
Diplopia
|
0.00%
0/12
|
0.00%
0/8
|
27.3%
3/11
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12
|
25.0%
2/8
|
9.1%
1/11
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12
|
12.5%
1/8
|
9.1%
1/11
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12
|
12.5%
1/8
|
18.2%
2/11
|
|
Immune system disorders
Allergy to insect sting
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
|
Infections and infestations
Viral pharyngitis
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
|
Infections and infestations
Viral tonsillitis
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
|
Nervous system disorders
Dizziness
|
0.00%
0/12
|
0.00%
0/8
|
9.1%
1/11
|
|
Nervous system disorders
Drowsiness
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/11
|
|
Infections and infestations
Acute pharyngitis
|
0.00%
0/12
|
0.00%
0/8
|
18.2%
2/11
|
|
Metabolism and nutrition disorders
Inappetence
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/11
|
|
Nervous system disorders
Equilibrium trouble
|
0.00%
0/12
|
0.00%
0/8
|
9.1%
1/11
|
|
Nervous system disorders
Intention tremor
|
0.00%
0/12
|
25.0%
2/8
|
0.00%
0/11
|
|
Nervous system disorders
Nystagmus
|
0.00%
0/12
|
0.00%
0/8
|
18.2%
2/11
|
|
Nervous system disorders
Seizures
|
8.3%
1/12
|
12.5%
1/8
|
0.00%
0/11
|
|
Psychiatric disorders
Aggression aggravated
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/11
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER