Parkinson Disease
Conditions
Keywords
Parkinson Disease, BIA 9-1067
Brief summary
To investigate the effect of BIA 9-1067 in steady-state conditions on the levodopa pharmacokinetics
Detailed description
Single centre, randomized, double-blind, gender-balanced, placebo-controlled study in 4 groups of healthy subjects
Interventions
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
25 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Availability for the entire study period and willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer prior to participation in the study. * Male or female volunteers. * Volunteers of at least 25 years of age but not older than 45 years. * Volunteers with body mass index (BMI) greater than or equal to 19 and below 30 kg/m2. * Volunteers who were healthy as determined by pre-study (at screening) medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG. * Volunteers who had clinical laboratory test results judged clinically acceptable (within the laboratory's stated normal range; if not within this range, they must had been without any clinical significance) at screening and admission to first treatment period. * Volunteers who had negative tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibodies (HCV Ab), and Human immunodeficiency viruses -1 and -2 antibodies (HIV-1 and HIV-2 Ab) at screening. * Volunteers who had negative screen of ethyl alcohol and drugs of abuse at screening and admission to the treatment period. * Volunteers who were non- or ex-smokers. For the purpose of this study, an ex-smoker is defined as someone who completely stopped smoking for at least 3 months before day 1 of this study. * Due to unknown risks and potential harm to the unborn fetus, sexually active men or women must have agreed to use a medically acceptable form of contraception throughout the study. * If female of childbearing potential, she had a negative HCG beta serum pregnancy test at screening and admission to each treatment period. * The informed consent form must have been signed by all volunteers, prior to their participation in the study.
Exclusion criteria
* Volunteers who did not conform to the above inclusion criteria, or in case of * Volunteers who had a clinically relevant surgical history. * Volunteers who had a clinically relevant family history. * Volunteers who had a history of relevant atopy. * Volunteers who had a significant infection or known inflammatory process at screening or admission to the treatment period. * Volunteers who had acute gastrointestinal symptoms at the time of screening or admission to the treatment period (e.g., nausea, vomiting, diarrhoea, heartburn). * Volunteers who were vegetarians, vegans or have medical dietary restrictions. * Volunteers who could not communicate reliably with the investigator. * Volunteers who were unlikely to co-operate with the requirements of the study. * History of hypersensitivity to BIA 9-1067, tolcapone, entacapone, levodopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs. * Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects. * History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability. * Presence or history of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, lymphatic, musculoskeletal, genitourinary, endocrine, immunologic, dermatologic or connective tissue disease. * Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases. * Presence of significant heart disease or disorder according to ECG. * Presence of suspicious undiagnosed skin lesions or a history of melanoma. * Previous history of Neuroleptic Malignant Syndrome (NMS) and/or nontraumatic rhabdomyolysis. * History of significant glaucoma. * Used of prescription medications including monoamine oxidase (MAO) inhibitors within 28 days before day 1 of the study. * Used of over-the-counter (OTC) products within 7 days before day 1 of the study. * Maintenance therapy with any drug, or significant history of drug dependency (drug abuse) or alcohol abuse (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic). * Any clinically significant illness in the previous 28 days before day 1 of this study. * Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study. * 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 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study. * Positive urine screening of ethyl alcohol or drugs of abuse at admission to the treatment period. * Any history of tuberculosis and/or prophylaxis for tuberculosis. * Positive results to HIV, HBsAg or anti-HCV tests. * Participation in any previous clinical study with BIA 9-1067. * Females who were pregnant according to a positive serum pregnancy test or were lactating. * Females of childbearing potential who refused to use an acceptable contraceptive regimen throughout the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax - Maximum Plasma Concentration | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h | Cmax - maximum plasma concentration Cmax (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Cmax (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Cmax (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® |
| Tmax - Time to Maximum Plasma Concentration | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h | Tmax - time to maximum plasma concentration Tmax (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Tmax (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Tmax (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® |
| AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h | AUC0-t - area under the plasma concentration-time curve from time 0 to last observed concentration 3-OMD - 3-O-methyl-dopa - metabolite of L-DOPA (levodopa) AUC0-t (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® AUC0-t (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® AUC0-t (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® |
| tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h | tEmax - time of occurrence of maximum observed effect on S-COMT activity COMT - Catechol-O-Methyltransferase |
| AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose | pre-dose and at the following times post-dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 and 24 h | AUEC0-24 - Area under the effect-time curve (AUEC) to 24 h post-dose. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28.
Placebo
levodopa/carbidopa
levodopa/benserazide | 14 |
| 5 mg BIA 9-1067 5 mg BIA 9-1067 once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28
BIA 9-1067
levodopa/carbidopa
levodopa/benserazide | 13 |
| 15 mg BIA 9-1067 15 mg BIA 9-1067 once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28
BIA 9-1067
levodopa/carbidopa
levodopa/benserazide | 13 |
| 30 mg BIA 9-1067 30 mg BIA 9-1067 once-daily for 28 days single-dose of levodopa/carbidopa 100/25 mg on Day 21 single-dose of levodopa/benserazide 100/25 mg on Day 28
BIA 9-1067
levodopa/carbidopa
levodopa/benserazide | 12 |
| Total | 52 |
Baseline characteristics
| Characteristic | Placebo | 5 mg BIA 9-1067 | 15 mg BIA 9-1067 | 30 mg BIA 9-1067 | 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 | 14 Participants | 13 Participants | 13 Participants | 12 Participants | 52 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 25 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 7 Participants | 6 Participants | 27 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 | 11 / 14 | 9 / 13 | 11 / 13 | 9 / 12 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 | 0 / 13 | 0 / 12 |
Outcome results
Primary
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point
AUC0-t - area under the plasma concentration-time curve from time 0 to last observed concentration 3-OMD - 3-O-methyl-dopa - metabolite of L-DOPA (levodopa) AUC0-t (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® AUC0-t (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® AUC0-t (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa®
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 h
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid levodopa pharmacokinetic data. In this study, 48 subjects completed the entire study and 49 had valid levodopa data (one subject had valid levodopa data until Day 21)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Sinemet® 100/25 | NA ng.h/mL | — |
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Prolopa® 100-25 | 2438 ng.h/mL | Standard Deviation 712 |
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Prolopa® 100/25 | NA ng.h/mL | — |
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Sinemet® 100/25 | 7631 ng.h/mL | Standard Deviation 1786 |
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Prolopa® 100/25 | 11371 ng.h/mL | Standard Deviation 3707 |
| Placebo | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Sinemet® 100/25 | 1837 ng.h/mL | Standard Deviation 593 |
| 5 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Sinemet® 100/25 | 5147 ng.h/mL | Standard Deviation 1534 |
| 5 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Sinemet® 100/25 | 223 ng.h/mL | Standard Deviation 58.2 |
| 5 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Prolopa® 100/25 | 6205 ng.h/mL | Standard Deviation 1458 |
| 5 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Prolopa® 100/25 | 232 ng.h/mL | Standard Deviation 82.4 |
| 5 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Sinemet® 100/25 | 3386 ng.h/mL | Standard Deviation 1449 |
| 5 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Prolopa® 100-25 | 4115 ng.h/mL | Standard Deviation 1547 |
| 15 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Sinemet® 100/25 | 872 ng.h/mL | Standard Deviation 412 |
| 15 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Prolopa® 100-25 | 3442 ng.h/mL | Standard Deviation 1225 |
| 15 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Prolopa® 100/25 | 3473 ng.h/mL | Standard Deviation 1962 |
| 15 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Sinemet® 100/25 | 2836 ng.h/mL | Standard Deviation 1495 |
| 15 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Sinemet® 100/25 | 2952 ng.h/mL | Standard Deviation 1003 |
| 15 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Prolopa® 100/25 | 836 ng.h/mL | Standard Deviation 497 |
| 30 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Prolopa® 100/25 | 1185 ng.h/mL | Standard Deviation 562 |
| 30 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Sinemet® 100/25 | 2753 ng.h/mL | Standard Deviation 889 |
| 30 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (Levodopa) Prolopa® 100-25 | 4056 ng.h/mL | Standard Deviation 1051 |
| 30 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Sinemet® 100/25 | 1751 ng.h/mL | Standard Deviation 988 |
| 30 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (3-OMD) Prolopa® 100/25 | 2623 ng.h/mL | Standard Deviation 1065 |
| 30 mg BIA 9-1067 | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point | AUC0-t (BIA 9-1067) Sinemet® 100/25 | 1101 ng.h/mL | Standard Deviation 525 |
Primary
AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose
AUEC0-24 - Area under the effect-time curve (AUEC) to 24 h post-dose.
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 h
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid levodopa pharmacokinetic data. In this study, 48 subjects completed the entire study and 49 had valid levodopa data (one subject had valid levodopa data until Day 21)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose | 906 pmol/mg Hb/h.h | Standard Deviation 276 |
| 5 mg BIA 9-1067 | AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose | 454 pmol/mg Hb/h.h | Standard Deviation 97.3 |
| 15 mg BIA 9-1067 | AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose | 319 pmol/mg Hb/h.h | Standard Deviation 134 |
| 30 mg BIA 9-1067 | AUEC0-24 - Area Under the Effect-time Curve (AUEC) to 24 h Post-dose | 226 pmol/mg Hb/h.h | Standard Deviation 177 |
Primary
Cmax - Maximum Plasma Concentration
Cmax - maximum plasma concentration Cmax (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Cmax (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Cmax (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa®
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 h
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid levodopa pharmacokinetic data. In this study, 48 subjects completed the entire study and 49 had valid levodopa data (one subject had valid levodopa data until Day 21)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Sinemet® 100/25 | 985 ng/mL | Standard Deviation 290 |
| Placebo | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Prolopa® 100-25 | 1704 ng/mL | Standard Deviation 682 |
| Placebo | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Sinemet® 100/25 | 456 ng/mL | Standard Deviation 130 |
| Placebo | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Prolopa® 100/25 | 688 ng/mL | Standard Deviation 230 |
| Placebo | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Sinemet® 100/25 | NA ng/mL | — |
| Placebo | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Prolopa® 100/25 | NA ng/mL | — |
| 5 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Prolopa® 100/25 | 95.5 ng/mL | Standard Deviation 41.1 |
| 5 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Prolopa® 100/25 | 360 ng/mL | Standard Deviation 96 |
| 5 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Sinemet® 100/25 | 1245 ng/mL | Standard Deviation 524 |
| 5 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Sinemet® 100/25 | 307 ng/mL | Standard Deviation 106 |
| 5 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Prolopa® 100-25 | 2100 ng/mL | Standard Deviation 907 |
| 5 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Sinemet® 100/25 | 75.0 ng/mL | Standard Deviation 39 |
| 15 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Prolopa® 100-25 | 1727 ng/mL | Standard Deviation 957 |
| 15 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Sinemet® 100/25 | 167 ng/mL | Standard Deviation 82.5 |
| 15 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Prolopa® 100/25 | 206 ng/mL | Standard Deviation 110.8 |
| 15 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Prolopa® 100/25 | 281 ng/mL | Standard Deviation 153.4 |
| 15 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Sinemet® 100/25 | 263 ng/mL | Standard Deviation 82.3 |
| 15 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Sinemet® 100/25 | 1200 ng/mL | Standard Deviation 607 |
| 30 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Sinemet® 100/25 | 310 ng/mL | Standard Deviation 115 |
| 30 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (BIA 9-1067) Prolopa® 100/25 | 370 ng/mL | Standard Deviation 181.7 |
| 30 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Prolopa® 100-25 | 1795 ng/mL | Standard Deviation 788 |
| 30 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Prolopa® 100/25 | 160 ng/mL | Standard Deviation 61.9 |
| 30 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (Levodopa) Sinemet® 100/25 | 944 ng/mL | Standard Deviation 256 |
| 30 mg BIA 9-1067 | Cmax - Maximum Plasma Concentration | Cmax (3-OMD) Sinemet® 100/25 | 115 ng/mL | Standard Deviation 54.5 |
Primary
tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity
tEmax - time of occurrence of maximum observed effect on S-COMT activity COMT - Catechol-O-Methyltransferase
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 h
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid levodopa pharmacokinetic data. In this study, 48 subjects completed the entire study and 49 had valid levodopa data (one subject had valid levodopa data until Day 21)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity | 8.12 hours | Standard Deviation 8.15 |
| 5 mg BIA 9-1067 | tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity | 2.71 hours | Standard Deviation 2.16 |
| 15 mg BIA 9-1067 | tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity | 4.67 hours | Standard Deviation 1.92 |
| 30 mg BIA 9-1067 | tEmax - Time of Occurrence of Maximum Observed Effect on S-COMT Activity | 3.50 hours | Standard Deviation 2.41 |
Primary
Tmax - Time to Maximum Plasma Concentration
Tmax - time to maximum plasma concentration Tmax (Levodopa) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Tmax (3-OMD) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa® Tmax (BIA 9-1067) Sinemet® or Prolopa® - following administration of Sinemet® or Prolopa®
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 h
Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid levodopa pharmacokinetic data. In this study, 48 subjects completed the entire study and 49 had valid levodopa data (one subject had valid levodopa data until Day 21)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Sinemet® 100/25 | 0.5 hours |
| Placebo | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Prolopa® 100-25 | 1.0 hours |
| Placebo | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Sinemet® 100/25 | 4.0 hours |
| Placebo | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Prolopa® 100/25 | 4.0 hours |
| Placebo | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Sinemet® 100/25 | NA hours |
| Placebo | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Prolopa® 100/25 | NA hours |
| 5 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Prolopa® 100/25 | 3.0 hours |
| 5 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Prolopa® 100/25 | 8.0 hours |
| 5 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Sinemet® 100/25 | 0.75 hours |
| 5 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Sinemet® 100/25 | 8.0 hours |
| 5 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Prolopa® 100-25 | 1.0 hours |
| 5 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Sinemet® 100/25 | 1.5 hours |
| 15 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Prolopa® 100-25 | 1.0 hours |
| 15 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Sinemet® 100/25 | 6.0 hours |
| 15 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Prolopa® 100/25 | 6.0 hours |
| 15 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Prolopa® 100/25 | 2.5 hours |
| 15 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Sinemet® 100/25 | 3.0 hours |
| 15 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Sinemet® 100/25 | 0.5 hours |
| 30 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Sinemet® 100/25 | 4.0 hours |
| 30 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (BIA 9-1067) Prolopa® 100/25 | 3.0 hours |
| 30 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Prolopa® 100-25 | 1.0 hours |
| 30 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Prolopa® 100/25 | 4.0 hours |
| 30 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (Levodopa) Sinemet® 100/25 | 1.0 hours |
| 30 mg BIA 9-1067 | Tmax - Time to Maximum Plasma Concentration | Tmax (3-OMD) Sinemet® 100/25 | 8.0 hours |