Parkinson's Disease (PD)
Conditions
Keywords
Parkinson's disease (PD), BIA 9-1067, Opicapone
Brief summary
The purpose of this study is to determine the effect of BIA 9 1067 (5 mg, 15 mg and 50 mg) in steady-state conditions on the levodopa pharmacokinetics of a single dose of immediate-release levodopa/carbidopa 100/25 mg and of a single dose of immediate-release levodopa/benserazide 100/25 mg.
Detailed description
A single-centre, randomized, double-blind, gender-balanced, placebo-controlled study in 4 groups of 18 healthy subjects each. This study consisted of a once-daily administration of BIA 9 1067 (5 mg, 15 mg or 50 mg) or placebo for 18 days. Twelve (12) hours after the BIA 9 1067 dose, a single-dose of levodopa/carbidopa 100/25 mg was administered on Day 11 and a single-dose of levodopa/benserazide 100/25 mg was administered on Day 18.
Interventions
DRUGBIA 9-1067 5 mg
OPC, Opicapone
DRUGBIA 9-1067 25 mg
OPC, Opicapone
DRUGlevodopa/carbidopa 100/25
immediate (standard) release levodopa/carbidopa 100/25
DRUGPlacebo
PLC, Placebo
DRUGlevodopa/benserazide 100/25 mg
immediate (standard) release levodopa/benserazide
Sponsors
Bial - Portela C S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* able to participate and willing to give written informed consent; * male and female subjects; * aged 18 to 45 years, inclusive; * body mass index (BMI) between 18 and 30 kg/m2; * healthy as determined by the Investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs, complete neurological examination and 12-lead electrocardiogram (ECG); * negative tests for hepatitis B surface (HBs) antigen, anti-hepatitis C virus (HCV), human immunodeficiency virus-1 (HIV-1) and HIV-2 antibodies at screening; * negative screen for drugs of abuse and alcohol at screening and admission to the treatment period; * non-smokers or ex-smokers for at least 3 months; * if sexually active, agreed to use a medically acceptable form of contraception throughout the study; * if female of childbearing potential, had a negative human chorionic gonadotropin (HCG) beta serum pregnancy test at screening and admission to the treatment period.
Exclusion criteria
* who did not conform to the above inclusion criteria, or in case of volunteers who had a clinically relevant surgical history, a clinically relevant family history; or who had a history of relevant atopy; * who had a significant infection or known inflammatory process at screening or admission to the treatment period; acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, heartburn) at the time of screening or admission to the treatment period; * who were vegetarians, vegans or had medical dietary restrictions; * who could not communicate reliably with the Investigator; * who were unlikely to co-operate with the requirements of the study; history of hypersensitivity to BIA 9 1067, tolcapone, entacapone, levodopa, carbidopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs; * any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, haematological, neurologic, or psychiatric disease; * any clinically significant illness in the previous 28 days before day 1 of this study; history of drug abuse within 1 year before study day 1; history of alcoholism within 1 year before day 1. * Consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° \[10%\] wine = 12 g; 4 cL of aperitif, 42° \[42%\] whiskey = 17 g; 25 cL glass of 3° \[3%\] beer = 7.5 g; 25 cL glass of 6° \[6%\] beer = 15 g); * poor motivation, intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with the protocol requirements or inability to cooperate adequately, inability to understand and to observe the instructions of the physician; * donation of blood (i.e., 450 mL) within 60 days before study day 1; * positive urine screening of ethyl alcohol or drugs of abuse upon admission to the treatment period; * any history of tuberculosis and/or prophylaxis for tuberculosis; positive results to HIV, hepatitis B surface antigen (HBsAg) or anti-HCV tests; * participation in any previous clinical study with BIA 9 1067; * if female, being pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. | Cmax - Maximum plasma concentration of levodopa following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11 |
| Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. | Tmax - Time to Reach maximum plasma concentration of levodopa following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11 |
| AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Carbidopa) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. | Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11 |
| AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Carbidopa) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. | AUC0-t - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to the last sampling time following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11 |
| Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide ) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. | Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18 |
| Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. | Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18 |
| AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Benserazide) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose. | Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18 |
| AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Benserazide) | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose | Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18 |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 3 capsules of placebo for 18 days levodopa/carbidopa 100/25 mg was administered on Day 11 levodopa/benserazide 100/25 mg was administered on Day 18.
levodopa/carbidopa 100/25: immediate (standard) release levodopa/carbidopa 100/25
Placebo: PLC, Placebo
levodopa/benserazide 100/25 mg: immediate (standard) release levodopa/benserazide | 18 |
| BIA 9-1067 5 mg 1 capsule of 5 mg + 2 capsules of placebo for 18 days levodopa/carbidopa 100/25 mg was administered on Day 11 levodopa/benserazide 100/25 mg was administered on Day 18.
BIA 9-1067 5 mg: OPC, Opicapone
levodopa/carbidopa 100/25: immediate (standard) release levodopa/carbidopa 100/25
Placebo: PLC, Placebo
levodopa/benserazide 100/25 mg: immediate (standard) release levodopa/benserazide | 19 |
| BIA 9-1067 15 mg 3 capsules of 5 mg for 18 days levodopa/carbidopa 100/25 mg was administered on Day 11 levodopa/benserazide 100/25 mg was administered on Day 18.
BIA 9-1067 5 mg: OPC, Opicapone
levodopa/carbidopa 100/25: immediate (standard) release levodopa/carbidopa 100/25
levodopa/benserazide 100/25 mg: immediate (standard) release levodopa/benserazide | 19 |
| BIA 9-1067 50 mg 2 capsules of BIA 9-1067 25 mg + 1 capsule of placebo for 18 days levodopa/carbidopa 100/25 mg was administered on Day 11 levodopa/benserazide 100/25 mg was administered on Day 18.
BIA 9-1067 25 mg: OPC, Opicapone
levodopa/carbidopa 100/25: immediate (standard) release levodopa/carbidopa 100/25
Placebo: PLC, Placebo
levodopa/benserazide 100/25 mg: immediate (standard) release levodopa/benserazide | 18 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | BIA 9-1067 5 mg | BIA 9-1067 15 mg | BIA 9-1067 50 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 19 Participants | 19 Participants | 18 Participants | 74 Participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 10 Participants | 9 Participants | 38 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 9 Participants | 9 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 18 | 12 / 19 | 9 / 19 | 5 / 18 |
| serious Total, serious adverse events | 1 / 18 | 0 / 19 | 0 / 19 | 0 / 18 |
Outcome results
Primary
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Benserazide)
Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Benserazide) | 2360.3 ng.h/mL | Standard Deviation 738.9 |
| BIA 9-1067 5 mg | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Benserazide) | 2660.9 ng.h/mL | Standard Deviation 593.2 |
| BIA 9-1067 15 mg | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Benserazide) | 3655.9 ng.h/mL | Standard Deviation 553.1 |
| BIA 9-1067 50 mg | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Benserazide) | 3979.5 ng.h/mL | Standard Deviation 1406.1 |
Primary
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Carbidopa)
Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Carbidopa) | 1861.3 ng.h/mL | Standard Deviation 466.5 |
| BIA 9-1067 5 mg | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Carbidopa) | 2332.3 ng.h/mL | Standard Deviation 634.9 |
| BIA 9-1067 15 mg | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Carbidopa) | 2736.8 ng.h/mL | Standard Deviation 767 |
| BIA 9-1067 50 mg | AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to Infinity (Levodopa/Carbidopa) | 3182.6 ng.h/mL | Standard Deviation 814.1 |
Primary
AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Benserazide)
Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Benserazide) | 2278.8 ng.h/mL | Standard Deviation 730.4 |
| BIA 9-1067 5 mg | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Benserazide) | 2549.8 ng.h/mL | Standard Deviation 586.6 |
| BIA 9-1067 15 mg | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Benserazide) | 3521.1 ng.h/mL | Standard Deviation 557.7 |
| BIA 9-1067 50 mg | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Benserazide) | 3819.7 ng.h/mL | Standard Deviation 1391.5 |
Primary
AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Carbidopa)
AUC0-t - Area under the plasma concentration-time curve (AUC) of levodopa from time zero to the last sampling time following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Carbidopa) | 1788.3 ng.h/mL | Standard Deviation 461.2 |
| BIA 9-1067 5 mg | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Carbidopa) | 2219.7 ng.h/mL | Standard Deviation 616.4 |
| BIA 9-1067 15 mg | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Carbidopa) | 2584.3 ng.h/mL | Standard Deviation 794.9 |
| BIA 9-1067 50 mg | AUC0-t - Area Under the Plasma Concentration-time Curve (AUC) of Levodopa From Time Zero to the Last Sampling Time at Which the Drug Concentration Was at or Above the Lower Limit of Quantification. (Levodopa/Carbidopa) | 2975.9 ng.h/mL | Standard Deviation 799 |
Primary
Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide )
Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide ) | 1770.3 ng/mL | Standard Deviation 741.2 |
| BIA 9-1067 5 mg | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide ) | 1379.8 ng/mL | Standard Deviation 605.1 |
| BIA 9-1067 15 mg | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide ) | 2118.3 ng/mL | Standard Deviation 573.4 |
| BIA 9-1067 50 mg | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide ) | 1813.7 ng/mL | Standard Deviation 811.3 |
Primary
Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa)
Cmax - Maximum plasma concentration of levodopa following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 966.6 ng/mL | Standard Deviation 313.2 |
| BIA 9-1067 5 mg | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 1026.8 ng/mL | Standard Deviation 445.2 |
| BIA 9-1067 15 mg | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 1097.9 ng/mL | Standard Deviation 353.2 |
| BIA 9-1067 50 mg | Cmax - Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 1019.7 ng/mL | Standard Deviation 282.1 |
Primary
Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide)
Levodopa pharmacokinetic parameters following a single oral administration of 100/25 mg levodopa/benserazide administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 18
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide) | 0.89 hours | Standard Deviation 0.47 |
| BIA 9-1067 5 mg | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide) | 1.08 hours | Standard Deviation 0.52 |
| BIA 9-1067 15 mg | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide) | 0.7 hours | Standard Deviation 0.3 |
| BIA 9-1067 50 mg | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Benserazide) | 1.08 hours | Standard Deviation 0.62 |
Primary
Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa)
Tmax - Time to Reach maximum plasma concentration of levodopa following a single oral administration of 100/25 mg levodopa/carbidopa administered 12 h after BIA 9-1067 (5 mg, 15 mg and 50 mg) or placebo on Day 11
Time frame: pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 0.78 hours | Standard Deviation 0.49 |
| BIA 9-1067 5 mg | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 1 hours | Standard Deviation 0.84 |
| BIA 9-1067 15 mg | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 0.95 hours | Standard Deviation 0.55 |
| BIA 9-1067 50 mg | Tmax - Time to Reach Maximum Plasma Concentration of Levodopa (Levodopa/Carbidopa) | 1 hours | Standard Deviation 0.59 |