Trial Outcomes & Findings for Pharmacokinetic-pharmacodynamic Interaction Between Each of Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Carbidopa (NCT NCT02169453)
NCT ID: NCT02169453
Last Updated: 2015-01-21
Results Overview
Cmax - Maximum observed plasma concentration of levodopa
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 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
2015-01-21
Participant Flow
Participant milestones
| Measure |
Group 1
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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
Group 2
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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
Group 3
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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
Group 4
Period 1: Placebo Period 2: BIA 9-1067 25 mg Period 3: BIA 9-1067 50 mg Period 4: BIA 9-1067 100 mg
Subjects were to attend four treatment periods and were to receive a different dose of BIA 9-1067 (25 mg, 50 mg and 100 mg) or placebo during each of these treatment periods.
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
3
|
|
Overall Study
25 mg BIA 9-1067
|
3
|
3
|
3
|
3
|
|
Overall Study
50 mg BIA 9-1067
|
3
|
3
|
2
|
3
|
|
Overall Study
100 mg BIA 9-1067
|
3
|
3
|
3
|
3
|
|
Overall Study
Placebo
|
3
|
3
|
3
|
3
|
|
Overall Study
COMPLETED
|
3
|
3
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetic-pharmacodynamic Interaction Between Each of Three Different Single Doses of BIA 9-1067 and a Single-dose of Controlled-release 100/25 mg Levodopa/Carbidopa
Baseline characteristics by cohort
| Measure |
Group 1
n=3 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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
Group 2
n=3 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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
Group 3
n=3 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 Sinemet® CR 100/25 (Single-dose of controlled-release levodopa/carbidopa 100/25 mg: 1 tablet of Sinemet® CR 100/25.)
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
Group 4
n=3 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
Subjects were to attend four treatment periods and were to receive a different dose of BIA 9-1067 (25 mg, 50 mg and 100 mg) or placebo during each of these treatment periods.
BIA 9-1067: OPC, Opicapone
Placebo: PLC, Placebo
Sinemet® CR 100/25: Controlled-release levodopa/carbidopa 100/25 mg
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
12 Participants
n=36 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
12 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-doseCmax - Maximum observed plasma concentration of levodopa
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=12 Participants
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=11 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=12 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=12 Participants
Placebo, PLC
|
|---|---|---|---|---|
|
Cmax - Maximum Observed Plasma Concentration
|
716 ng/mL
Standard Deviation 201.9
|
673 ng/mL
Standard Deviation 269.9
|
570 ng/mL
Standard Deviation 136.2
|
554 ng/mL
Standard Deviation 220.5
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-doseAUC0-t - Area under the plasma concentration-time curve to last measurable time point for levodopa
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=12 Participants
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=11 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=12 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=12 Participants
Placebo, PLC
|
|---|---|---|---|---|
|
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point
|
1886 ng.h/mL
Standard Deviation 396.1
|
1997 ng.h/mL
Standard Deviation 389.4
|
2059 ng.h/mL
Standard Deviation 372.7
|
1575 ng.h/mL
Standard Deviation 521.3
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-doseAUC0-∞ - Area under the plasma concentration-time curve extrapolated to infinity for levodopa
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=12 Participants
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=11 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=12 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=12 Participants
Placebo, PLC
|
|---|---|---|---|---|
|
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity
|
1986 ng.h/mL
Standard Deviation 395.2
|
2144 ng.h/mL
Standard Deviation 437.4
|
2215 ng.h/mL
Standard Deviation 381.0
|
1677 ng.h/mL
Standard Deviation 541.7
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-doseEmax - Maximum inhibition of Catechol-O-Methyltransferase (COMT) activity
Outcome measures
| Measure |
BIA 9-1067 25 mg
n=12 Participants
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=11 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=12 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=12 Participants
Placebo, PLC
|
|---|---|---|---|---|
|
Emax - Maximum Inhibition of COMT Activity
|
16.5 pmol/mg Hb/h
Standard Deviation 10.8
|
7.44 pmol/mg Hb/h
Standard Deviation 7.42
|
3.16 pmol/mg Hb/h
Standard Deviation 4.97
|
39.3 pmol/mg Hb/h
Standard Deviation 16.0
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-doseOutcome measures
| Measure |
BIA 9-1067 25 mg
n=12 Participants
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=11 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=12 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=12 Participants
Placebo, PLC
|
|---|---|---|---|---|
|
tEmax - Time of Occurrence of Emax
|
4.92 hours
Standard Deviation 2.71
|
3.59 hours
Standard Deviation 1.95
|
2.33 hours
Standard Deviation 0.985
|
7.17 hours
Standard Deviation 8.95
|
PRIMARY outcome
Timeframe: pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 h post-doseOutcome measures
| Measure |
BIA 9-1067 25 mg
n=12 Participants
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=11 Participants
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=12 Participants
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=12 Participants
Placebo, PLC
|
|---|---|---|---|---|
|
AUEC0-24 - Area Under the Effect-time Curve From t=0h to t=24h
|
621 pmol/mg Hb/h.h
Standard Deviation 300
|
427 pmol/mg Hb/h.h
Standard Deviation 214
|
363 pmol/mg Hb/h.h
Standard Deviation 201
|
1144 pmol/mg Hb/h.h
Standard Deviation 445
|
Adverse Events
BIA 9-1067 25 mg
Serious events: 0 serious events
Other events: 6 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: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
BIA 9-1067 25 mg
n=12 participants at risk
BIA 9-1067 25 mg OPC Opicapone
|
BIA 9-1067 50 mg
n=11 participants at risk
BIA 9-1067 50 mg OPC Opicapone
|
BIA 9-1067 100 mg
n=12 participants at risk
BIA 9-1067 100 mg OPC Opicapone
|
Placebo
n=12 participants at risk
Placebo, PLC
|
|---|---|---|---|---|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Cardiac disorders
Sinus arrhythmia
|
0.00%
0/12
|
0.00%
0/11
|
8.3%
1/12
|
0.00%
0/12
|
|
Eye disorders
Foreign body sensation in eyes
|
0.00%
0/12
|
0.00%
0/11
|
8.3%
1/12
|
0.00%
0/12
|
|
Eye disorders
Vision blurred
|
0.00%
0/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Abdominal pain
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
2/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Dry mouth
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12
|
0.00%
0/11
|
8.3%
1/12
|
8.3%
1/12
|
|
General disorders
Application site erythema
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/12
|
0.00%
0/12
|
|
General disorders
Fatigue
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
16.7%
2/12
|
|
General disorders
Feeling hot
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
General disorders
Gait disturbance
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Infections and infestations
Influenza
|
0.00%
0/12
|
0.00%
0/11
|
8.3%
1/12
|
0.00%
0/12
|
|
Investigations
Blood creatine phosphokinase increased
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Investigations
Electrocardiogram PR interval
|
0.00%
0/12
|
0.00%
0/11
|
8.3%
1/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Trismus
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Nervous system disorders
Dysgeusia
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Nervous system disorders
Headache
|
16.7%
2/12
|
0.00%
0/11
|
8.3%
1/12
|
25.0%
3/12
|
|
Nervous system disorders
Hypoaesthesia
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Nervous system disorders
Somnolence
|
16.7%
2/12
|
18.2%
2/11
|
0.00%
0/12
|
25.0%
3/12
|
|
Nervous system disorders
Tremor
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Psychiatric disorders
Impatience
|
8.3%
1/12
|
9.1%
1/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Psychiatric disorders
Insomnia
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Psychiatric disorders
Nightmare
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Renal and urinary disorders
Terminal dribbling
|
0.00%
0/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12
|
0.00%
0/11
|
0.00%
0/12
|
8.3%
1/12
|
|
Vascular disorders
Hot flush
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/12
|
0.00%
0/12
|
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