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    Summary
    EudraCT Number:2009-012897-12
    Sponsor's Protocol Code Number:BIA-91067-202
    National Competent Authority:Romania - National Agency for Medicines and Medical Devices
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-03-30
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedRomania - National Agency for Medicines and Medical Devices
    A.2EudraCT number2009-012897-12
    A.3Full title of the trial
    A double-blind, randomised, placebo-controlled study to investigate the tolerability and the effect of three multiple-dose regimens of BIA 9-1067 on the levodopa pharmacokinetics, catechol-0-methyltransferase activity and motor response in parkinson´s disease patients treated with levodopa/dopa-decarboxylase
    inhibitor
    A.4.1Sponsor's protocol code numberBIA-91067-202
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBIAL-Portela & Ca, SA
    B.1.3.4CountryPortugal
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBIA 9-1067
    D.3.2Product code BIA 9-1067
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 923287-50-7
    D.3.9.2Current sponsor codeBIA 9-1067
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBIA 9-1067
    D.3.2Product code BIA 9-1067
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 923287-50-7
    D.3.9.2Current sponsor codeBIA 9-1067
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name SINEMET 25/100
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme, Lda
    D.2.1.2Country which granted the Marketing AuthorisationPortugal
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLEVODOPA
    D.3.9.1CAS number 59-92-7
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 28860-95-9
    D.3.9.3Other descriptive nameANHYDROUS CARBIDOPA
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Restex Tabletten
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Pharma AG
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLEVODOPA
    D.3.9.1CAS number 59-92-7
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBENSERAZIDE HYDROCHLORIDE
    D.3.9.1CAS number 14919-77-8
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Parkinson’s Disease
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10013113
    E.1.2Term Disease Parkinson's
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the effect of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30 mg, once-daily) on the levodopa
    pharmacokinetics, in comparison to placebo, in Parkinson’s Disease (PD) patients with motor fluctuations.
    E.2.2Secondary objectives of the trial
    - To investigate the tolerability and safety of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30 mg, oncedaily),
    in comparison with placebo, in PD patients with motor fluctuations.
    - To investigate the effect of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30 mg, once-daily) on motor
    response to standard-release levodopa/carbidopa 100 mg/25 mg or levodopa/benserazide 100 mg/25 mg, in
    comparison with placebo, in PD patients with motor fluctuations.
    - To investigate the effect of repeated dosing of BIA 9-1067 (5 mg, 15 mg and 30
    mg, once-daily) on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity, in comparison with
    placebo, in PD patients with motor fluctuations.
    - To investigate the pharmacokinetics of BIA 9-1067 following repeated dosing (5 mg, 15 mg and 30 mg, oncedaily)
    in PD patients with motor fluctuations.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    At screening (admission to the baseline period):
    - Male or female of non-childbearing potential (by reason of surgery or postmenopausal);
    - Age ≥ 30 years;
    - A diagnosis of PD according to the UK PDS Brain Bank diagnostic criteria (bradykinesia and at least one of the
    following: muscular rigidity, rest tremor and postural instability);
    - Predictable signs of end-of-dose deterioration despite “optimal” levodopa/carbidopa or levodopa/benserazide
    therapy;
    - Modified Hoehn and Yahr stage of less than 5 in the “off” state; mean duration of “off” state ≥1.5 h during
    waking hours (based on historical information);
    - Results of clinical laboratory tests acceptable by the investigator (not clinically significant for the well-being of
    the patient or for the purpose of the study);
    - Able and willing to give written informed consent.
    At randomisation (completion of the baseline period):
    - Been treated with a stable regimen of 3 to 8 doses per day of standard-release levodopa/carbidopa 100/25 mg
    (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) for at least 1 week prior to randomisation;
    - Mean duration of “off” state ≥1.5 h during waking hours (average of recordings of last 3 evaluable days on
    patient’s diary);
    - Concomitant anti-Parkinsonian medication (other than apomorphine, entacapone or tolcapone) in stable doses
    for at least 4 weeks prior to admission;
    E.4Principal exclusion criteria
    At screening (admission to the baseline period):
    - Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome);
    - Treated with entacapone, tolcapone, neuroleptics, antidepressants (except serotonin-specific reuptake inhibitors
    or imipraminics [desipramine, imipramine, clomipramine and amitriptyline]), monoamine oxidase inhibitors
    (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation or
    rasagiline up to 1 mg/day) or antiemetics (except domperidone) within 2 weeks prior to admission;
    - Treated with any investigational product within 1 month prior to admission (or within 5 half-lives, whichever is
    longer);
    - A psychiatric or any medical condition that might place him/her at increased risk or interfere with assessments;
    - Known hypersensitivity to any of the ingredients of the investigational products;
    - A history of abuse of alcohol, drugs or medications within the last 2 years;
    - A clinically relevant ECG abnormality;
    - A history or current evidence of heart disease, including but not limited to myocardial infarction, angina,
    congestive heart failure and cardiac arrhythmia;
    - Unstable concomitant disease being treated with changing doses of medication;
    - A history or current evidence of any relevant disease in the context of this study, i.e., with respect to the safety
    of the patient (e.g., hepatic impairment) or related to the study conditions;
    - A test positive for the HIV-1 or HIV-2 antibodies, or hepatitis B surface antigen (HbsAg), or hepatitis C
    antibody (HCVAb);
    - Donated blood or received blood or blood products within the 6 months prior to admission;
    - Pregnant, breast-feeding or of childbearing potential;
    - Other condition or circumstance that, in the opinion of the investigator, may
    compromise the patient’s ability to comply with the study protocol.
    At randomisation (completion of the baseline period):
    - Treated with levodopa/DDCI in a 10:1 ratio or in a controlled-release formulation during the baseline period;
    - Treated with apomorphine during the baseline period;
    - A clinically relevant ECG abnormality.
    E
    E.5 End points
    E.5.1Primary end point(s)
    - for levodopa, 3-OMD, BIA 9-1067 and BIA 9-1079: maximum observed plasma concentration (Cmax); time of
    occurrence of Cmax (tmax); area under the plasma concentration-time curve (AUC) from time zero to 6 h postdose
    (AUC0-6), and AUC from time zero to the last quantified concentration (AUC0-t), calculated by the linear
    trapezoidal rule; AUC from time zero to infinity (AUC0-∞), calculated from AUC0-t + (Clast/λz).
    - maximum inhibition of S-COMT activity (Emax), time of occurrence of Emax (tEmax); maximum percent (%)
    inhibition of S-COMT activity, calculated as [(E0-Emax)/E0]*100
    - Second levodopa test versus first levodopa test: Change in “on” duration, change in time to “on”, and change in
    time to best “on”
    - BIA 9-1067/Placebo period versus baseline period: Change in absolute “off”-time (patient’s diaries), change
    in the percentage of “off”-time (patient’s diaries), change in the percentage of “on” time without troublesome
    dyskinesia (patient’s diaries), change in UPDRS Section I, change in UPDRS Section II at “off” stage, change in
    UPDRS Section III, change in UPDRS Section V, change in UPDRS Section VI, investigator’s global assessment
    of change; patient’s global assessment of change, and change in daily number of doses of levodopa/DDCI.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    provided in protocol
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 32
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    provided in protocol
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2009-11-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-12-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2010-06-24
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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