FindTrial
Sign In

Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa

Pharmacokinetic Interaction Between BIA 9-1067 and Standard-release Levodopa/Carbidopa in Healthy Subjects

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01533077
Enrollment
18
Registered
2012-02-15
Start date
2009-03-31
Completion date
2010-02-28
Last updated
2015-12-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson Disease

Keywords

Parkinson Disease, BIA 9-1067

Brief summary

To investigate the pharmacokinetics of levodopa when administered concomitantly with BIA 9-1067 or 1 hour after.

Detailed description

Single-centre, open-label, randomized, gender-balanced, crossover study with four consecutive single-dose treatment periods.

Interventions

DRUGBIA 9-1067

50 mg of BIA 9-1067 (single-dose)

DRUGSinemet® 100/25 mg

immediate-release levodopa/carbidopa 100/25 (single-dose).

Sponsors

Bial - Portela C S.A.
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 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 18 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. * 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 within 84 days before day 1 of the study. * 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

MeasureTime frameDescription
Cmax - Maximum Observed Plasma Concentration (L-DOPA)pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)
Tmax - Time of Occurrence of Cmax Maximum Observed Plasma Concentration (L-DOPA)pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA). For tmax = time to Cmax values are presented as median with range values.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (L-DOPA)pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)
AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (L-DOPA)pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)
Cmax - Maximum Observed Plasma Concentration (3-OMD)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after doseMean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)
Tmax - Time to Occurrence of Cmax (3-OMD)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dosePharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD). For tmax = time to Cmax values are presented as median with range values.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (3-OMD)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (3-OMD)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)
Cmax - Maximum Observed Plasma Concentration (Carbidopa)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of carbidopa
Tmax - Time to Occurrence of Cmax (Carbidopa)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (Carbidopa)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of carbidopa
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (Carbidopa)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dosePharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.
Cmax - Maximum Observed Plasma Concentration (BIA 9-1067)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of BIA 9-1067
Tmax - Time to Occurrence of Cmax (BIA 9-1067)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Pharmacokinetic parameters of BIA 9-1067. For tmax = time to Cmax values are presented as median with range values.
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (BIA 9-1067)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of BIA 9-1067
AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (BIA 9-1067)Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.Mean pharmacokinetic parameters of BIA 9-1067

Countries

Canada

Participant flow

Participants by arm

ArmCount
Group 1
Period 1: BIA 9-1067 50 mg Period 2: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 3: BIA 9-1067 50 mg + Sinemet® 100/25 Period 4: Sinemet® 100/25 BIA 9-1067: 50 mg of BIA 9-1067 (single-dose) Sinemet® 100/25 mg: immediate-release levodopa/carbidopa 100/25 (single-dose).
5
Group 2
Period 1: Sinemet® 100/25 Period 2: BIA 9-1067 50 mg Period 3: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 4: BIA 9-1067 50 mg + Sinemet® 100/25 BIA 9-1067: 50 mg of BIA 9-1067 (single-dose) Sinemet® 100/25 mg: immediate-release levodopa/carbidopa 100/25 (single-dose).
5
Group 3
Period 1: BIA 9-1067 50 mg + Sinemet® 100/25 Period 2: Sinemet® 100/25 Period 3: BIA 9-1067 50 mg Period 4: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg BIA 9-1067: 50 mg of BIA 9-1067 (single-dose) Sinemet® 100/25 mg: immediate-release levodopa/carbidopa 100/25 (single-dose).
4
Group 4
Period 1: Sinemet® 100/25 1 h after the BIA 9-1067 50 mg Period 2: BIA 9-1067 50 mg + Sinemet® 100/25 Period 3: Sinemet® 100/25 Period 4: BIA 9-1067 50 mg BIA 9-1067: 50 mg of BIA 9-1067 (single-dose) Sinemet® 100/25 mg: immediate-release levodopa/carbidopa 100/25 (single-dose).
4
Total18

Baseline characteristics

CharacteristicGroup 1Group 2Group 3Group 4Total
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
5 Participants5 Participants4 Participants4 Participants18 Participants
Sex: Female, Male
Female
2 Participants2 Participants2 Participants2 Participants8 Participants
Sex: Female, Male
Male
3 Participants3 Participants2 Participants2 Participants10 Participants

Adverse events

Event typeEG000
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
8 / 1810 / 188 / 168 / 17
serious
Total, serious adverse events
0 / 180 / 180 / 160 / 17

Outcome results

Primary

AUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (L-DOPA)

Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)

Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (L-DOPA)2397 ng.h/mLStandard Deviation 741
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (L-DOPA)2730 ng.h/mLStandard Deviation 913
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-∞ - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (L-DOPA)2603 ng.h/mLStandard Deviation 836
Primary

AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (3-OMD)

Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (3-OMD)11193 ng.h/mLStandard Deviation 3187
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (3-OMD)7730 ng.h/mLStandard Deviation 2578
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (3-OMD)89962 ng.h/mLStandard Deviation 2803
Primary

AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (BIA 9-1067)

Mean pharmacokinetic parameters of BIA 9-1067

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (BIA 9-1067)2165 ng.h/mLStandard Deviation 913
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (BIA 9-1067)2360 ng.h/mLStandard Deviation 1281
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (BIA 9-1067)2678 ng.h/mLStandard Deviation 1334
Primary

AUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (Carbidopa)

Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (Carbidopa)668 ng.h/mLStandard Deviation 224
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (Carbidopa)683 ng.h/mLStandard Deviation 253
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-∞ - Area Under the Plasma Concentration-time Curve Extrapolated to Infinity (Carbidopa)745 ng.h/mLStandard Deviation 337
Primary

AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (3-OMD)

Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (3-OMD)10296 ng.h/mLStandard Deviation 3151
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (3-OMD)6940 ng.h/mLStandard Deviation 2504
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (3-OMD)8149 ng.h/mLStandard Deviation 2809
Primary

AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (BIA 9-1067)

Mean pharmacokinetic parameters of BIA 9-1067

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (BIA 9-1067)2094 ng.h/mLStandard Deviation 904
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (BIA 9-1067)2130 ng.h/mLStandard Deviation 1248
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (BIA 9-1067)2245 ng.h/mLStandard Deviation 1171
Primary

AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (Carbidopa)

Mean pharmacokinetic parameters of carbidopa

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (Carbidopa)656 ng.h/mLStandard Deviation 226
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (Carbidopa)670 ng.h/mLStandard Deviation 253
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (Carbidopa)732 ng.h/mLStandard Deviation 335
Primary

AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (L-DOPA)

Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)

Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (L-DOPA)2289 ng.h/mLStandard Deviation 729
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (L-DOPA)2611 ng.h/mLStandard Deviation 916
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyAUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point (L-DOPA)2459 ng.h/mLStandard Deviation 825
Primary

Cmax - Maximum Observed Plasma Concentration (3-OMD)

Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgCmax - Maximum Observed Plasma Concentration (3-OMD)490 ng/mLStandard Deviation 175
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hCmax - Maximum Observed Plasma Concentration (3-OMD)336 ng/mLStandard Deviation 127
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyCmax - Maximum Observed Plasma Concentration (3-OMD)401 ng/mLStandard Deviation 141
Primary

Cmax - Maximum Observed Plasma Concentration (BIA 9-1067)

Mean pharmacokinetic parameters of BIA 9-1067

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgCmax - Maximum Observed Plasma Concentration (BIA 9-1067)648 ng/mLStandard Deviation 264
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hCmax - Maximum Observed Plasma Concentration (BIA 9-1067)625 ng/mLStandard Deviation 346
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyCmax - Maximum Observed Plasma Concentration (BIA 9-1067)628 ng/mLStandard Deviation 295
Primary

Cmax - Maximum Observed Plasma Concentration (Carbidopa)

Mean pharmacokinetic parameters of carbidopa

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgCmax - Maximum Observed Plasma Concentration (Carbidopa)134 ng/mLStandard Deviation 56.2
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hCmax - Maximum Observed Plasma Concentration (Carbidopa)136 ng/mLStandard Deviation 62
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyCmax - Maximum Observed Plasma Concentration (Carbidopa)142 ng/mLStandard Deviation 71.3
Primary

Cmax - Maximum Observed Plasma Concentration (L-DOPA)

Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)

Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEAN)Dispersion
Sinemet® 100/25 mgCmax - Maximum Observed Plasma Concentration (L-DOPA)1070 ng/mLStandard Deviation 328
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hCmax - Maximum Observed Plasma Concentration (L-DOPA)1105 ng/mLStandard Deviation 363
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyCmax - Maximum Observed Plasma Concentration (L-DOPA)1198 ng/mLStandard Deviation 294
Primary

Tmax - Time of Occurrence of Cmax Maximum Observed Plasma Concentration (L-DOPA)

Pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA). For tmax = time to Cmax values are presented as median with range values.

Time frame: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEDIAN)
Sinemet® 100/25 mgTmax - Time of Occurrence of Cmax Maximum Observed Plasma Concentration (L-DOPA)1.0 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hTmax - Time of Occurrence of Cmax Maximum Observed Plasma Concentration (L-DOPA)1.0 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyTmax - Time of Occurrence of Cmax Maximum Observed Plasma Concentration (L-DOPA)0.5 hours
Primary

Tmax - Time to Occurrence of Cmax (3-OMD)

Pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD). For tmax = time to Cmax values are presented as median with range values.

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEDIAN)
Sinemet® 100/25 mgTmax - Time to Occurrence of Cmax (3-OMD)6.00 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hTmax - Time to Occurrence of Cmax (3-OMD)5.00 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyTmax - Time to Occurrence of Cmax (3-OMD)5.00 hours
Primary

Tmax - Time to Occurrence of Cmax (BIA 9-1067)

Pharmacokinetic parameters of BIA 9-1067. For tmax = time to Cmax values are presented as median with range values.

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEDIAN)
Sinemet® 100/25 mgTmax - Time to Occurrence of Cmax (BIA 9-1067)2.50 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hTmax - Time to Occurrence of Cmax (BIA 9-1067)3.50 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyTmax - Time to Occurrence of Cmax (BIA 9-1067)4.00 hours
Primary

Tmax - Time to Occurrence of Cmax (Carbidopa)

Pharmacokinetic parameters of carbidopa. For tmax = time to Cmax values are presented as median with range values.

Time frame: Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.

Population: According to the protocol, the pharmacokinetic population should include all subjects who had valid data for all treatment periods. In this study, 18 subjects completed 2 treatment periods, 17 subjects completed 3 treatment periods and 16 subjects completed all 4 treatment periods.

ArmMeasureValue (MEDIAN)
Sinemet® 100/25 mgTmax - Time to Occurrence of Cmax (Carbidopa)3.00 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 hTmax - Time to Occurrence of Cmax (Carbidopa)3.00 hours
BIA 9-1067 50 mg + Sinemet® 100/25 mg ConcomitantlyTmax - Time to Occurrence of Cmax (Carbidopa)3.00 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026