The Effect of BIA 9-1067 at Steady-state on the Levodopa Pharmacokinetics
Condition: Parkinson's Disease (PD)
MeSH terms: Parkinson Disease
Intervention: BIA 9-1067; Entacapone; Placebo; Levodopa/carbidopa
Intervention description: BIA 9-1067 25 mg and 50 mg; Entacapone (ENT), over-encapsulated tablet 200 mg; PLC, placebo; Levodopa/carbidopa, tablet 100/25 mg
Intervention MeSH terms: Levodopa; Carbidopa; Opicapone; Entacapone
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Parkinson's disease (PD); BIA 9-1067; Opicapone

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).
    

Eligibility criteria:

        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.