Pharmacokinetic Interaction Between BIA 9-1067 and Standa... | NCT01533077

NCT01533077

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1	Experimental	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	Drug: BIA 9-1067 Drug: Sinemet® 100/25 mg
Group 2	Experimental	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	Drug: BIA 9-1067 Drug: Sinemet® 100/25 mg
Group 3	Experimental	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	Drug: BIA 9-1067 Drug: Sinemet® 100/25 mg
Group 4	Experimental	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	Drug: BIA 9-1067 Drug: Sinemet® 100/25 mg

Name	Type	Description	Arm Group Labels	Other Names
BIA 9-1067	Drug	50 mg of BIA 9-1067 (single-dose)	Group 1 Group 2 Group 3 Group 4

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cmax - Maximum Observed Plasma Concentration (L-DOPA)	Mean pharmacokinetic parameters of L-beta-3,4-dihydroxyphenylalanine (levodopa) (L-DOPA)	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
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.	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
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)	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
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)	pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose.
Cmax - Maximum Observed Plasma Concentration (3-OMD)	Mean pharmacokinetic parameters of 3-O-methyl-levodopa (3-OMD)	Pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 h after dose
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.

Eligibility Module

Eligibility Criteria

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.

Contacts/Locations Module

Name	Affiliation	Role
Eric Sicard, MD	Algorithme Pharma Inc	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Algorithme Pharma Inc.		Mount Royal	Quebec	H3P 3P1	Canada

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	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).
FG001	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).
FG002	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).
FG003	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).

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0005 subjects FG0015 subjects FG0024 subjects FG0034 subjects
BIA 9-1067 50 mg		FG0005 subjects FG0015 subjects FG0024 subjects FG0034 subjects
Sinemet® 100/25		FG0004 subjects FG0015 subjects FG0024 subjects FG0034 subjects
BIA 9-1067 50 mg + Sinemet® 100/25		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects
Sinemet® 100/25 1 h After the BIA 9-1067		FG0005 subjects FG0015 subjects FG0024 subjects FG0034 subjects
COMPLETED		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects
NOT COMPLETED		FG0001 subjects FG0011 subjects FG0020 subjects FG0030 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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).
BG001

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 Observed Plasma Concentration (L-DOPA)

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

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.

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	Sinemet® 100/25 mg	Levodopa 100 mg Carbidopa 25 mg
OG001	BIA 9-1067 50 mg + Sinemet® 100/25 mg Separated 1 h

Adverse Events Module

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BIA 9-1067 50 mg	BIA 9-1067 50 mg.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Head of Clinical Research	Bial - Portela & Cª, S.A.	+351 229 866 100		jose.rocha@bial.com

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D010300	Parkinson Disease

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

Intervention Browse Module

ID	Term
C549349	opicapone
C009265	carbidopa, levodopa drug combination
D007980	Levodopa
D002230	Carbidopa

ID	Term
D004295	Dihydroxyphenylalanine
D002395	Catecholamines
D000588	Amines
D009930	Organic Chemicals

Masking Info

BIA 9-1067 50 mg + Sinemet® 100/25 mg separated 1 h BIA 9-1067 Levodopa 100 mg Carbidopa 25 mg

EG0010 affected18 at risk

EG0020 affected16 at risk

EG0031 affected17 at risk