Trial Outcomes & Findings for Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Benserazide (NCT NCT02169466)
NCT ID: NCT02169466
Last Updated: 2015-11-03
Results Overview
Primary pharmacokinetic parameter: Levodopa maximum observed plasma concentration (Cmax) (ng/mL)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.
Results posted on
2015-11-03
Participant Flow
Participant milestones
| Measure |
BIA 9-1067: 25, 50, 100, Placebo
Period 1: BIA 9-1067 25 mg Period 2: BIA 9-1067 50 mg Period 3: BIA 9-1067 100 mg Period 4: Placebo
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
BIA 9-1067: 50, 100, Placebo, 25
Period 1: BIA 9-1067 50 mg Period 2: BIA 9-1067 100 mg Period 3: Placebo Period 4: BIA 9-1067 25 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
BIA 9-1067: 100, Placebo, 25, 50
Period 1: BIA 9-1067 100 mg Period 2: Placebo Period 3: BIA 9-1067 25 mg Period 4: BIA 9-1067 50 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
BIA 9-1067: Placebo, 25, 50, 100
Period 1: Placebo Period 2: BIA 9-1067 25 mg Period 3: BIA 9-1067 50 mg Period 4: BIA 9-1067 100 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
5
|
5
|
|
Overall Study
25 mg BIA 9-1067
|
6
|
5
|
5
|
5
|
|
Overall Study
50 mg BIA 9-1067
|
6
|
6
|
5
|
5
|
|
Overall Study
100 mg BIA 9-1067
|
6
|
6
|
5
|
5
|
|
Overall Study
Placebo
|
5
|
6
|
5
|
5
|
|
Overall Study
COMPLETED
|
5
|
5
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetic-pharmacodynamic Interaction Between Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Benserazide
Baseline characteristics by cohort
| Measure |
BIA 9-1067: 25, 50, 100, Placebo
n=6 Participants
Period 1: BIA 9-1067 25 mg Period 2: BIA 9-1067 50 mg Period 3: BIA 9-1067 100 mg Period 4: Placebo
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
BIA 9-1067: 50, 100, Placebo, 25
n=6 Participants
Period 1: BIA 9-1067 50 mg Period 2: BIA 9-1067 100 mg Period 3: Placebo Period 4: BIA 9-1067 25 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
BIA 9-1067: 100, Placebo, 25, 50
n=5 Participants
Period 1: BIA 9-1067 100 mg Period 2: Placebo Period 3: BIA 9-1067 25 mg Period 4: BIA 9-1067 50 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
BIA 9-1067: Placebo, 25, 50, 100
n=5 Participants
Period 1: Placebo Period 2: BIA 9-1067 25 mg Period 3: BIA 9-1067 50 mg Period 4: BIA 9-1067 100 mg
BIA 9-1067/Placebo was to be administered concomitantly with the dose of Madopar® HBS (Single-dose of controlled-release levodopa/benserazide 100/25 mg: 1 capsule of Madopar® HBS.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Madopar® HBS: controlled-release levodopa 100 mg/benserazide 25 mg
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.Population: According to the protocol, the "pharmacokinetic population" should include all subjects who had valid data for all treatment periods.
Primary pharmacokinetic parameter: Levodopa maximum observed plasma concentration (Cmax) (ng/mL)
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=20 Participants
BIA 9-1067 25 mg OPC Opicapone Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
BIA 9-1067 50 mg
n=20 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=20 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=20 Participants
Placebo, PLC Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
|---|---|---|---|---|
|
Cmax - Maximum Observed Plasma Concentration of Levodopa
|
314 ng/mL
Standard Deviation 110
|
266 ng/mL
Standard Deviation 77.5
|
263 ng/mL
Standard Deviation 94.9
|
260 ng/mL
Standard Deviation 119
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.Population: According to the protocol, the "pharmacokinetic population" should include all subjects who had valid data for all treatment periods.
Primary pharmacokinetic parameter: Area under the plasma concentration-time curve for levodopa
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=20 Participants
BIA 9-1067 25 mg OPC Opicapone Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
BIA 9-1067 50 mg
n=20 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=20 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=20 Participants
Placebo, PLC Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
|---|---|---|---|---|
|
AUC0-t - Area Under the Plasma Concentration-time Curve
|
1084 ng.h/mL
Standard Deviation 398
|
1064 ng.h/mL
Standard Deviation 365
|
1140 ng.h/mL
Standard Deviation 592
|
933 ng.h/mL
Standard Deviation 422
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.Population: According to the protocol, the "pharmacokinetic population" should include all subjects who had valid data for all treatment periods.
Primary pharmacokinetic parameter: Area under the plasma concentration-time curve from time zero to infinity for levodopa
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=19 Participants
BIA 9-1067 25 mg OPC Opicapone Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
BIA 9-1067 50 mg
n=20 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=19 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=19 Participants
Placebo, PLC Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
|---|---|---|---|---|
|
AUC0-∞ - AUC From Time Zero to Infinity
|
1190 ng.h/mL
Standard Deviation 441
|
1181 ng.h/mL
Standard Deviation 373
|
1326 ng.h/mL
Standard Deviation 604
|
1086 ng.h/mL
Standard Deviation 380
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-dose.Population: According to the protocol, the "pharmacokinetic population" should include all subjects who had valid data for all treatment periods.
Primary pharmacokinetic parameter: tmax - time to Cmax
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=20 Participants
BIA 9-1067 25 mg OPC Opicapone Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
BIA 9-1067 50 mg
n=20 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=20 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=20 Participants
Placebo, PLC Of the initialy enrolled 21 subjects, 1 subject was not considered for the accountability as he was withdrawn from study participation
|
|---|---|---|---|---|
|
Tmax - Time to Cmax
|
2.50 hours
Interval 1.0 to 4.0
|
2.50 hours
Interval 1.0 to 4.0
|
2.00 hours
Interval 1.0 to 6.0
|
2.00 hours
Interval 1.0 to 4.0
|
Adverse Events
BIA 9-1067 25 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
BIA 9-1067 50 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
BIA 9-1067 100 mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BIA 9-1067 25 mg
n=21 participants at risk
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=22 participants at risk
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=22 participants at risk
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=21 participants at risk
Placebo, PLC
|
|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
4.5%
1/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
|
Infections and infestations
Oral herpes
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
4.5%
1/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
4.5%
1/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
|
Infections and infestations
Respiratory tract infection
|
4.8%
1/21 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
|
Investigations
Blood creatine phosphokinase increased
|
4.8%
1/21 • Just before drug administration until 72 h post-dose
|
9.1%
2/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
|
Nervous system disorders
Headache
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
4.5%
1/22 • Just before drug administration until 72 h post-dose
|
4.8%
1/21 • Just before drug administration until 72 h post-dose
|
|
Psychiatric disorders
Depression
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
4.8%
1/21 • Just before drug administration until 72 h post-dose
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
4.5%
1/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
0.00%
0/22 • Just before drug administration until 72 h post-dose
|
4.5%
1/22 • Just before drug administration until 72 h post-dose
|
0.00%
0/21 • Just before drug administration until 72 h post-dose
|
Additional Information
Head of Clinical Research
Bial - Portela & Cª, S.A.
Phone: +351 229 866 100
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER