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The Effect of BIA 9-1067 at Steady-state on the Levodopa Pharmacokinetics

Sponsor
Bial - Portela C S.A. (Industry)
Overall Status
Completed
CT.gov ID
NCT02170376
Collaborator
(none)
80
Enrollment
1
Location
5
Arms
4
Duration (Months)
20
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effect of repeated dosing of once-daily 25, 50 and 75 mg opicapone (OPC, development code BIA 9-1067) on the levodopa pharmacokinetics (PK), in comparison to placebo and 200 mg entacapone (ENT).

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This study was a single-centre, randomized, double-blind, gender-balanced, placebo-controlled study in 4 groups of 20 healthy subjects each (10 male and 10 female). The clinical part included a screening examination within 3 weeks before the first institutionalization, an ambulatory period of 11 days (from Day 1 evening to Day 11 evening), during which the subjects returned to the clinical unit every evening, followed by an institutionalization of 1.5 days (from Day 11 evening to Day 13 morning (i.e. 14 h after the third administration of levodopa/carbidopa). Then, a follow-up visit at 5 to 9 days after collection of the last PK blood sample (i.e. Day 13). The maximum total duration of the clinical study, including the 21-day screening period and the post-study follow-up, was expected to be about 39 to 43 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
The Effect of BIA 9-1067 at Steady-state on the Levodopa Pharmacokinetics When Administered With Immediate-release 100/25 mg Levodopa/Carbidopa in Healthy Subjects
Study Start Date :
Sep 1, 2011
Actual Primary Completion Date :
Jan 1, 2012
Actual Study Completion Date :
Jan 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group 1

Placebo once-daily for 11 days 200 mg entacapone concomitantly with levodopa/carbidopa on Day 12

Drug: Entacapone
Entacapone (ENT), over-encapsulated tablet 200 mg
Other Names:
  • Comtan®, ENT

    • Drug: Placebo
    PLC, placebo
    Other Names:
  • PLC, placebo

    • Drug: Levodopa/carbidopa
    Levodopa/carbidopa, tablet 100/25 mg
    Other Names:
  • Sinemet®

    		•
    Experimental: Group 2

    25 mg BIA 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12

    Drug: BIA 9-1067
    BIA 9-1067 25 mg and 50 mg
    Other Names:
  • Opicapone, OPC

    • Drug: Placebo
    PLC, placebo
    Other Names:
  • PLC, placebo

    • Drug: Levodopa/carbidopa
    Levodopa/carbidopa, tablet 100/25 mg
    Other Names:
  • Sinemet®

    		•
    Experimental: Group 3

    50 mg 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12

    Drug: BIA 9-1067
    BIA 9-1067 25 mg and 50 mg
    Other Names:
  • Opicapone, OPC

    • Drug: Placebo
    PLC, placebo
    Other Names:
  • PLC, placebo

    • Drug: Levodopa/carbidopa
    Levodopa/carbidopa, tablet 100/25 mg
    Other Names:
  • Sinemet®

    		•
    Experimental: Group 4

    75 mg 9-1067 once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12

    Drug: BIA 9-1067
    BIA 9-1067 25 mg and 50 mg
    Other Names:
  • Opicapone, OPC

    • Drug: Placebo
    PLC, placebo
    Other Names:
  • PLC, placebo

    • Drug: Levodopa/carbidopa
    Levodopa/carbidopa, tablet 100/25 mg
    Other Names:
  • Sinemet®

    		•
    Placebo Comparator: Group 5

    placebo once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12

    Drug: Placebo
    PLC, placebo
    Other Names:
  • PLC, placebo

    • Drug: Levodopa/carbidopa
    Levodopa/carbidopa, tablet 100/25 mg
    Other Names:
  • Sinemet®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Cmax - Maximum Plasma Concentration of Levodopa [pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration]

      Cmax - Maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

    2. Tmax - Time of Occurrence of Maximum Plasma Concentration [pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration]

      Tmax - Time to Reach maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone

    3. AUC0-∞ - Area Under the Concentration-time Curve From Time Zero up to Infinity With Extrapolation of the Terminal Phase [pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration]

      AUC0-∞ of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

    4. AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time (t) Corresponding to the Last Quantifiable Concentration. [pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration]

      AUC0-t - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

    5. AUC0-5 - AUC Over 5 Hours [pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration]

      AUC0-5 - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

    6. t1/2 - Terminal Plasma Half-life [pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration]

      t1/2 - Terminal plasma half-life of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Healthy male and female volunteers 18 to 45 years old (inclusive),

    • Body Mass Index (BMI) in normal range (18-30 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 ECG (electrocardiogram),

    • Negative tests for Hepatitis B surface antigen (HBsAG), anti-Hepatitis C virus (HCV) antibodies and Human immunodeficiency virus (HIV) -1 and HIV-2 antibodies at screening,

    • Negative screen for drugs of abuse and alcohol at screening and admission to the treatment period,

    • If of childbearing potential (i.e. except if they had been sterilized for at least 3 months or postmenopausal for at least one year - the menopause was defined by a follicule stimulating hormone (FSH) level > 30 IU/L): used a non hormonal acceptable contraception method, i.e. intra-uterine device, condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for all the duration of the study,

    • If female of childbearing potential, had a negative human chorionic gonadotropin (HCG) beta serum pregnancy test at screening and urinary pregnancy test at admission to both ambulatory and confinement periods,

    • Non-smokers or ex-smokers for at least 3 months,

    • Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study,

    • Provision of written informed consent to participate as shown by a signature on the volunteer consent form,

    • Registered with the French Social Security in agreement with the French law on biomedical experimentation

    Exclusion Criteria:

    • 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; had a history of relevant atopy,

    • Had a significant infection or known inflammatory process at screening or admission to the treatment period; acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission to the treatment period,

    • Were vegetarians, vegans or had medical dietary restrictions,

    • Could not communicate reliably with the Investigator,

    • Were unlikely to co-operate with the requirements of the study; history of hypersensitivity to OPC, tolcapone, ENT, levodopa, carbidopa, benserazide or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs,

    • Had any significant cardiovascular (e.g. hypertension), hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidemia), immunologic, dermatological, hematological, neurological, or psychiatric disease,

    • Presented 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,

    • Had taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 2 weeks prior to the dose administration,

    • Consumed 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,

    • Drank more than 8 cups daily of beverage containing caffeine,

    • Had 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,

    • Had received any experimental drug within the exclusion period defined in the National Register for Healthy Volunteers of the French Ministry of Health,

    • Forfeited their freedom by administrative or legal award or were under guardianship,

    • Had undergone surgery or had donated blood (i.e. 450 mL) within 12 weeks before study Day 1,

    • Had positive urine screening of ethyl alcohol or drugs of abuse upon admission to the treatment period,

    • Had 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 OPC,

    • If female, was pregnant or breast-feeding.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 SGS aster Paris France 75015

    Sponsors and Collaborators

    • Bial - Portela C S.A.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bial - Portela C S.A.
    ClinicalTrials.gov Identifier:
    NCT02170376
    Other Study ID Numbers:
    • BIA-91067-124
    First Posted:
    Jun 23, 2014
    Last Update Posted:
    Sep 20, 2016
    Last Verified:
    Jul 1, 2016
    Keywords provided by Bial - Portela C S.A.
    Parkinson's disease (PD)
    BIA 9-1067
    Opicapone
    Additional relevant MeSH terms:
    Parkinson Disease
    Levodopa
    Carbidopa
    Opicapone
    Entacapone

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Group 1: Placebo Then Entacapone/Levodopa Group 2: BIA 25 mg Then Placebo/Levodopa/Carbidopa Group 3: BIA 50 mg Then Placebo/Levodopa/Carbidopa Group 4: BIA 75 mg Then Placebo/Levodopa/Carbidopa Group 5: Placebo Then Levodopa/Carbidopa
    Arm/Group Description Placebo once-daily for 11 days 200 mg entacapone concomitantly with levodopa/carbidopa on Day 12 Entacapone: Entacapone (ENT), over-encapsulated tablet 200 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 25 mg BIA 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 50 mg 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 75 mg 9-1067 once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg placebo once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12 Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg
    Period Title: Overall Study
    STARTED 16 16 16 16 16
    Pharmacokinetic Population 16 15 16 16 16
    COMPLETED 16 15 16 16 16
    NOT COMPLETED 0 1 0 0 0

    Baseline Characteristics

    Arm/Group Title Group 1 Group 2 Group 3 Group 4 Group 5 Total
    Arm/Group Description Placebo once-daily for 11 days 200 mg entacapone concomitantly with levodopa/carbidopa on Day 12 Entacapone: Entacapone (ENT), over-encapsulated tablet 200 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 25 mg BIA 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 50 mg 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 75 mg 9-1067 once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg placebo once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12 Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg Total of all reporting groups
    Overall Participants 16 16 16 16 16 80
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    16
    100%
    16
    100%
    16
    100%
    16
    100%
    16
    100%
    80
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    8
    50%
    8
    50%
    8
    50%
    8
    50%
    8
    50%
    40
    50%
    Male
    8
    50%
    8
    50%
    8
    50%
    8
    50%
    8
    50%
    40
    50%

    Outcome Measures

    1. Primary Outcome
    Title Cmax - Maximum Plasma Concentration of Levodopa
    Description Cmax - Maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
    Time Frame pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo OPC 25 mg OPC 50 mg OPC 75 mg ENT 200 mg
    Arm/Group Description Placebo: PLC, placebo OPC: BIA 9-1067 25 mg OPC: BIA 9-1067 50 mg OPC: BIA 9-1067 25 mg and 50 mg Entacapone (ENT), over-encapsulated tablet 200 mg
    Measure Participants 16 15 16 16 16
    Post First Dose
    1047
    (340)
    1203
    (453)
    1030
    (400)
    1057
    (335)
    876
    (328)
    Post Second Dose
    1550
    (542)
    1619
    (762)
    1974
    (847)
    2113
    (868)
    1437
    (569)
    Post Third Dose
    1268
    (532)
    1393
    (627)
    1346
    (337)
    1658
    (435)
    1303
    (518)
    2. Primary Outcome
    Title Tmax - Time of Occurrence of Maximum Plasma Concentration
    Description Tmax - Time to Reach maximum plasma concentration of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone
    Time Frame pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo OPC 25 mg OPC 50 mg OPC 75 mg ENT 200 mg
    Arm/Group Description Placebo: PLC, placebo OPC: BIA 9-1067 25 mg OPC: BIA 9-1067 50 mg OPC: BIA 9-1067 25 mg and 50 mg Entacapone (ENT), over-encapsulated tablet 200 mg
    Measure Participants 16 15 16 16 16
    Post First Dose
    1.31
    (0.854)
    1.13
    (0.790)
    1.34
    (1.01)
    1.28
    (0.515)
    1.13
    (0.695)
    Post Second Dose
    0.875
    (0.465)
    1.20
    (0.862)
    1.06
    (0.892)
    1.19
    (0.854)
    0.906
    (0.491)
    Post Third Dose
    1.69
    (0.964)
    1.33
    (0.699)
    1.34
    (0.65)
    1.31
    (0.854)
    1.59
    (0.861)
    3. Primary Outcome
    Title AUC0-∞ - Area Under the Concentration-time Curve From Time Zero up to Infinity With Extrapolation of the Terminal Phase
    Description AUC0-∞ of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
    Time Frame pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo OPC 25 mg OPC 50 mg OPC 75 mg ENT 200 mg
    Arm/Group Description Placebo: PLC, placebo OPC: BIA 9-1067 25 mg OPC: BIA 9-1067 50 mg OPC: BIA 9-1067 25 mg and 50 mg Entacapone (ENT), over-encapsulated tablet 200 mg
    Measure Participants 16 15 16 16 16
    Post First Dose
    2305
    (391)
    3732
    (1418)
    3363
    (1042)
    3998
    (1275)
    2752
    (540)
    Post Second Dose
    3070
    (396)
    4967
    (2003)
    5727
    (1495)
    6213
    (1440)
    4367
    (1463)
    Post Third Dose
    3299
    (433)
    5614
    (2467)
    5912
    (1478)
    7177
    (1835)
    4707
    (363)
    4. Primary Outcome
    Title AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Time (t) Corresponding to the Last Quantifiable Concentration.
    Description AUC0-t - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
    Time Frame pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo OPC 25 mg OPC 50 mg OPC 75 mg ENT 200 mg
    Arm/Group Description Placebo: PLC, placebo OPC: BIA 9-1067 25 mg OPC: BIA 9-1067 50 mg OPC: BIA 9-1067 25 mg and 50 mg Entacapone (ENT), over-encapsulated tablet 200 mg
    Measure Participants 16 15 16 16 16
    Post First Dose
    1985
    (346)
    2665
    (867)
    2383
    (699)
    2829
    (794)
    2041
    (671)
    Post Second Dose
    2774
    (353)
    3678
    (1455)
    4151
    (1070)
    4597
    (1041)
    3445
    (1128)
    Post Third Dose
    3123
    (447)
    5391
    (2444)
    5685
    (1466)
    6928
    (1797)
    4366
    (1426)
    5. Primary Outcome
    Title AUC0-5 - AUC Over 5 Hours
    Description AUC0-5 - of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
    Time Frame pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo OPC 25 mg OPC 50 mg OPC 75 mg ENT 200 mg
    Arm/Group Description Placebo: PLC, placebo OPC: BIA 9-1067 25 mg OPC: BIA 9-1067 50 mg OPC: BIA 9-1067 25 mg and 50 mg Entacapone (ENT), over-encapsulated tablet 200 mg
    Measure Participants 16 15 16 16 16
    Post First Dose
    1985
    (346)
    2665
    (867)
    2383
    (699)
    2829
    (794)
    2042
    (669)
    Post Second Dose
    2774
    (353)
    3678
    (1455)
    4151
    (1070)
    4597
    (1041)
    3446
    (1125)
    Post Third Dose
    2719
    (492)
    3802
    (1549)
    3940
    (1022)
    4882
    (1246)
    3468
    (1108)
    6. Primary Outcome
    Title t1/2 - Terminal Plasma Half-life
    Description t1/2 - Terminal plasma half-life of levodopa (mean pharmacokinetic parameter) following first oral administration of 100/25 mg levodopa/carbidopa on Day 12 with 25, 50 and 75 mg OPC or placebo and 200 mg Entacapone.
    Time Frame pre-first dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0 and 5.0 h post-first and -second levodopa/carbidopa administration, and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 8.0 and 14.0 h post-third levodopa/carbidopa administration

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo OPC 25 mg OPC 50 mg OPC 75 mg ENT 200 mg
    Arm/Group Description Placebo: PLC, placebo OPC: BIA 9-1067 25 mg OPC: BIA 9-1067 50 mg OPC: BIA 9-1067 25 mg and 50 mg Entacapone (ENT), over-encapsulated tablet 200 mg
    Measure Participants 16 15 16 16 16
    Post First Dose
    1.46
    (0.406)
    2.47
    (0.830)
    2.47
    (0.098)
    2.39
    (0.556)
    2.11
    (0.626)
    Post Second Dose
    1.41
    (0.136)
    2.23
    (0.385)
    2.46
    (0.312)
    2.23
    (0.513)
    2.09
    (0.486)
    Post Third Dose
    1.74
    (0.349)
    2.56
    (0.440)
    2.75
    (0.513)
    2.70
    (0.462)
    2.20
    (0.632)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Group 1 Group 2 Group 3 Group 4 Group 5
    Arm/Group Description Placebo once-daily for 11 days 200 mg entacapone concomitantly with levodopa/carbidopa on Day 12 Entacapone: Entacapone (ENT), over-encapsulated tablet 200 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 25 mg BIA 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 50 mg 9-1067 once-daily for 11 days Placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg 75 mg 9-1067 once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12 BIA 9-1067: BIA 9-1067 25 mg and 50 mg Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg placebo once-daily for 11 days placebo concomitantly with levodopa/carbidopa on Day 12 Placebo: PLC, placebo Levodopa/carbidopa: Levodopa/carbidopa, tablet 100/25 mg
    All Cause Mortality
    Group 1 Group 2 Group 3 Group 4 Group 5
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Group 1 Group 2 Group 3 Group 4 Group 5
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Group 1 Group 2 Group 3 Group 4 Group 5
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/16 (56.3%) 5/16 (31.3%) 8/16 (50%) 8/16 (50%) 11/16 (68.8%)
    Cardiac disorders
    Atrioventricular Block Second Degree 1/16 (6.3%) 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%)
    Palpitations 1/16 (6.3%) 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%)
    Ear and labyrinth disorders
    Vertigo 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%) 0/16 (0%)
    Gastrointestinal disorders
    Abdominal Pain 1/16 (6.3%) 1/16 (6.3%) 1/16 (6.3%) 1/16 (6.3%) 1/16 (6.3%)
    Diarrhoea 0/16 (0%) 0/16 (0%) 2/16 (12.5%) 0/16 (0%) 0/16 (0%)
    Flatulence 0/16 (0%) 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%)
    Nausea 5/16 (31.3%) 3/16 (18.8%) 8/16 (50%) 8/16 (50%) 4/16 (25%)
    Odynophagia 0/16 (0%) 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%)
    Vomiting 1/16 (6.3%) 3/16 (18.8%) 2/16 (12.5%) 3/16 (18.8%) 1/16 (6.3%)
    Infections and infestations
    Rhinitis 0/16 (0%) 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%)
    Musculoskeletal and connective tissue disorders
    Muscle Spasms 1/16 (6.3%) 1/16 (6.3%) 0/16 (0%) 0/16 (0%) 0/16 (0%)
    Nervous system disorders
    Dizziness 0/16 (0%) 1/16 (6.3%) 1/16 (6.3%) 0/16 (0%) 2/16 (12.5%)
    Headache 5/16 (31.3%) 2/16 (12.5%) 2/16 (12.5%) 1/16 (6.3%) 2/16 (12.5%)
    Somnolence 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%) 1/16 (6.3%)
    Reproductive system and breast disorders
    Dysmenorrhoea 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%) 2/16 (12.5%)
    Respiratory, thoracic and mediastinal disorders
    Pityriasis 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Cold Sweat 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%) 0/16 (0%)
    Purpura 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%) 1/16 (6.3%)
    Vascular disorders
    Hot Flush 0/16 (0%) 0/16 (0%) 3/16 (18.8%) 2/16 (12.5%) 1/16 (6.3%)
    Varicophlebitis 0/16 (0%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%) 0/16 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Head of Clinical Research
    Organization Bial - Portela & Cª, S.A.
    Phone +351 229 866 100
    Email jose.rocha@bial.com
    Responsible Party:
    Bial - Portela C S.A.
    ClinicalTrials.gov Identifier:
    NCT02170376
    Other Study ID Numbers:
    • BIA-91067-124
    First Posted:
    Jun 23, 2014
    Last Update Posted:
    Sep 20, 2016
    Last Verified:
    Jul 1, 2016