Effect of Three Multiple-dose Regimens of BIA 9 1067 at S... | NCT02169414

NCT02169414

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BIA 9-1067 5 mg	Experimental	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.	Drug: BIA 9-1067 5 mg Drug: levodopa/carbidopa 100/25 Drug: Placebo Drug: levodopa/benserazide 100/25 mg
BIA 9-1067 15 mg	Experimental	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.	Drug: BIA 9-1067 5 mg Drug: levodopa/carbidopa 100/25 Drug: levodopa/benserazide 100/25 mg
BIA 9-1067 50 mg	Experimental	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.	Drug: BIA 9-1067 25 mg Drug: levodopa/carbidopa 100/25 Drug: Placebo Drug: levodopa/benserazide 100/25 mg
Placebo	Placebo Comparator	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.	Drug: levodopa/carbidopa 100/25 Drug: Placebo Drug: levodopa/benserazide 100/25 mg

Name	Type	Description	Arm Group Labels	Other Names
BIA 9-1067 5 mg	Drug	OPC, Opicapone	BIA 9-1067 15 mg BIA 9-1067 5 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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 (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	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-∞ - 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	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 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	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 (Levodopa/Benserazide )

Eligibility Module

Eligibility Criteria

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.

Facility	Status	City	State	ZIP	Country	Contacts
BIOTRIAL		Rennes		F-35034	France

Arm/Group Information

ID	Title	Description
FG000	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
FG001	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
FG002	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
FG003	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

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Placebo	3 capsules of placebo for 18 days levodopa/carbidopa 100/25 mg was administered on Day 11 Levodopa/carbidopa 100/25: immediate (standard) release levodopa/carbidopa 100/25 Placebo: PLC, Placebo
OG001	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 BIA 9-1067 5 mg: OPC, Opicapone. Levodopa/carbidopa 100/25: immediate (standard) release levodopa/carbidopa 100/25 Placebo: PLC, Placebo

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases

ID	Term
C549349	opicapone
D007980	Levodopa
C009265	carbidopa, levodopa drug combination
D001545	Benserazide
C005177	benserazide, levodopa drug combination

ID	Term
D004295	Dihydroxyphenylalanine
D002395	Catecholamines
D000588	Amines
D009930	Organic Chemicals