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    The EU Clinical Trials Register currently displays   41210   clinical trials with a EudraCT protocol, of which   6750   are clinical trials conducted with subjects less than 18 years old.
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    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2016-003456-70
    Sponsor's Protocol Code Number:CTH-302
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-12-07
    Trial 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 ConcernedSpain - AEMPS
    A.2EudraCT number2016-003456-70
    A.3Full title of the trial
    An Open-Label, Randomized, Crossover Trial utilizing a Single-Blinded Rater to evaluate APL-130277 compared to s.c. Apomorphine in Levodopa Responsive Subjects with Parkinson’s Disease Complicated by Motor Fluctuations
    Ensayo abierto, cruzado y aleatorizado, con enmascaramiento de un único evaluador, para evaluar APL-130277 frente a apomorfina subcutánea en pacientes que han respondido a la levodopa con enfermedad de Parkinson agravada por las fluctuaciones motoras
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial to compare APL-130277 sublingual film to Subcutaneous Apomorphine in Parkinson’s Disease patients
    Un ensayo clínico para comparar, la película sublingual de APL-130277 frente a la Apomorfina en sujetos con Enfermedad de Pakinson.
    A.4.1Sponsor's protocol code numberCTH-302
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSunovion Pharmaceuticals Inc.
    B.1.3.4CountryUnited States
    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 supportSunovion Pharmaceuticals Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationINC Research UK Limited
    B.5.2Functional name of contact pointPatricia Rodriguez Sanz
    B.5.3 Address:
    B.5.3.1Street AddressRiver View, The Meadows Business Park, Station Approach, Blackwater
    B.5.3.2Town/ cityCamberley, Surrey
    B.5.3.3Post codeGU17 AB
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+3491708 8615
    B.5.6E-mailPatricia.Rodriguezsanz@INCResearch.com
    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 nameApomorphine hydrochloride
    D.3.2Product code APL-130277
    D.3.4Pharmaceutical form Sublingual film
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSublingual use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.2Current sponsor codeAPL-130277
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 RoleComparator
    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 APO-go
    D.2.1.1.2Name of the Marketing Authorisation holderBritannia Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 names.c. apomorphine
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 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 nameApomorphine hydrochloride
    D.3.2Product code APL-130277
    D.3.4Pharmaceutical form Sublingual film
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSublingual use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.2Current sponsor codeAPL-130277
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 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 nameApomorphine hydrochloride
    D.3.2Product code APL-130277
    D.3.4Pharmaceutical form Sublingual film
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSublingual use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.2Current sponsor codeAPL-130277
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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: 5
    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 nameApomorphine hydrochloride
    D.3.2Product code APL-130277
    D.3.4Pharmaceutical form Sublingual film
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSublingual use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.2Current sponsor codeAPL-130277
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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: 6
    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 nameApomorphine hydrochloride
    D.3.2Product code APL-130277
    D.3.4Pharmaceutical form Sublingual film
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSublingual use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.2Current sponsor codeAPL-130277
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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: 7
    D.1.2 and D.1.3IMP RoleComparator
    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 APO-go
    D.2.1.1.2Name of the Marketing Authorisation holderBritannia Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 names.c. apomorphine
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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: 8
    D.1.2 and D.1.3IMP RoleComparator
    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 APO-go
    D.2.1.1.2Name of the Marketing Authorisation holderBritannia Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 names.c. apomorphine
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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: 9
    D.1.2 and D.1.3IMP RoleComparator
    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 APO-go
    D.2.1.1.2Name of the Marketing Authorisation holderBritannia Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 names.c. apomorphine
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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: 10
    D.1.2 and D.1.3IMP RoleComparator
    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 APO-go
    D.2.1.1.2Name of the Marketing Authorisation holderBritannia Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 names.c. apomorphine
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNApomorphine hydrochloride
    D.3.9.1CAS number 41372-20-7
    D.3.9.3Other descriptive nameAPOMORPHINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB12924MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 placeboSublingual film
    D.8.4Route of administration of the placeboSublingual use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Levodopa Responsive Patients with Parkinson’s Disease Complicated by Motor Fluctuations ("OFF episodes")
    Pacientes que han respondido a la levodopa con enfermedad de Parkinson agravada por las fluctuaciones motoras ( "episodios OFF")
    E.1.1.1Medical condition in easily understood language
    Central nervous system disease affecting the movement
    Enfermedad del sistema nervioso central que afecta al movimiento
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10034006
    E.1.2Term Parkinson's disease aggravated
    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
    The primary objective is to demonstrate the preference of APL 130277 as a therapy for the acute and intermittent management of “OFF” episodes in subjects with Parkinson’s disease (PD) in the titration period and in an open label crossover period compared to subcutaneous (s.c.) apomorphine (in PART A and PART B).
    El objetivo principal es demostrar la preferencia de APL-130277 como tratamiento para el manejo agudo e intermitente de los episodios «OFF» en sujetos con la enfermedad de Parkinson (EP) en el periodo de ajuste de la dosis y en un periodo de tratamiento sin enmascaramiento con grupos cruzados en comparación con apomorfina subcutánea (s.c.) (en las PARTES A y B).
    E.2.2Secondary objectives of the trial
    The secondary objective is to demonstrate the superior efficacy of APL-130277 as a therapy for the acute and intermittent management of “OFF” episodes in subjects with PD compared to s.c. apomorphine (in PART B).
    El objetivo secundario es demostrar la superioridad de la eficacia de APL-130277 como tratamiento para el manejo agudo e intermitente de los episodios «OFF» en sujetos con EP en comparación con apomorfina s.c. (PARTE B).
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Optional Pharmacokinetic (PK) evaluation : Blood draws for APL-130277 and s.c. apomorphine PK analyses will occur during PART B at V2, V3, V5, and V6 at selected sites (dependent on feasibility). Blood draws will occur at t = 0 (just prior to dosing) and at t = 10, 20, 30, 60, 90, 120, 180 and 240 minutes post-dose. Sampling should occur as close as possible to the target time. Subjects must consent in order to participate in optional PK sub-study
    Evaluación farmacocinética (FC) opcional: Recogida de sangre para análisis farmacocinética de APL-130277 y Apomorfina s.c. se harán durante la PARTE B en las visitas V2, V3, V5 y V6 en el centro ( según visita de selección). La recogida de muestra de sangre se hará en t=0 (justo antes de la administración de la dosis) y en t = 10, 20, 30, 60, 90, 120, 180 y 240 minutos después de la administración de la dosis. La recogida de la muestra debe realizarse lo más cerca posible al tiempo objetivo. Los sujetos deben de dar su consentimiento para poder participar en el sub estudio opcional de FC.
    E.3Principal inclusion criteria
    1) Male or female ≥ 18 years of age.
    2) Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria.1
    3) Clinically meaningful response to L Dopa as determined by the Investigator.
    4) Receiving stable doses of L Dopa/carbidopa and/or L Dopa/benserazide and/or L Dopa/carbidopa/entacapone (immediate or chronic release) administered at least 4 times per day OR Rytary™ administered at least 3 times per day, and on stable doses for at least 4 weeks before the initial Screening Visit (SV1). Adjunctive PD medication regimens are permitted but must be maintained at a stable dose for at least 4 weeks prior to SV1 with the exception of monoamine oxidase B (MAO B) inhibitors, which must be maintained at a stable level for at least 8 weeks prior to SV1.
    5) No planned medication change(s) or surgical intervention anticipated during the course of study.
    6) Subjects must experience at least one well defined “OFF” episode per day with a total daily “OFF” time duration of > 2 hours during the waking day, based on judgment of physician and subject self assessment.
    7) Subject must have predictable morning “OFF” periods.
    8) Subject and where appropriate, caregiver, must be trained in completing the home dosing diary and able to recognize “ON” and “OFF” states.
    9) Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
    10) Mini–Mental State Examination (MMSE) score >25.
    11) Female subject of childbearing potential and male subject with female partner of childbearing potential, must agree to use an effective and medically acceptable form of birth control (see Section 10.3.1) throughout the study period. Note: Continued use of an effective and medically acceptable form of birth control is recommended through 30 days after study completion
    12) Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study related procedures to complete the study.
    13) Able to understand the consent form, and to provide written informed consent.
    14) Must be approved as a satisfactory candidate by the Enrollment Adjudication Committee (EAC).
    1.Hombres y mujeres de ≥18 años de edad.
    2.Diagnóstico clínico de EP idiopática, de conformidad con los criterios del UK Brain Bank
    3.Respuesta significativa desde el punto de vista clínico a la levodopa, determinada por el investigador.
    4.En tratamiento con dosis estables de levodopa/carbidopa y/o levodopa/benserazida y/o levodopa/carbidopa/entacapona (de liberación inmediata o controlada) administradas al menos 4 veces al día O BIEN Rytary™ administrada al menos 3 veces al día, y en dosis estables durante al menos 4 semanas antes de la visita inicial de selección (VS1). Se permiten los tratamientos complementarios de la EP, pero deben mantenerse a una dosis estable durante al menos 4 semanas antes de la VS1, con la excepción de que los inhibidores de la monoaminooxidasa B (MAO-B) deben mantenerse en un nivel estable durante al menos 8 semanas antes de la VS1.
    5.No se prevén cambios en el tratamiento farmacológico ni intervenciones quirúrgicas durante el estudio.
    6.Los sujetos deben experimentar al menos un episodio «OFF» bien definido al día y la duración total diaria de los episodios «OFF» debe ser >2 horas durante las horas de vigilia, sobre la base del criterio del médico y la autoevaluación del sujeto.
    7.El sujeto debe presentar periodos «OFF» previsibles por las mañanas.
    8.Deberá indicarse al sujeto y, cuando proceda, al cuidador cómo cumplimentar el diario de administración en el domicilio y estos deberán ser capaces de reconocer los estados «ON» y «OFF».
    9.Estadio III o menos en la escala de Hoehn y Yahr modificada en el estado «ON».
    10.Puntuación en el miniexamen cognoscitivo (MEC) de >25.
    11.Los sujetos de sexo femenino en edad fértil o los sujetos varones con parejas fértiles deben comprometerse a utilizar un método anticonceptivo eficaz y médicamente aceptable (consulte la sección 10.3.1)durante el periodo del estudio.Nota:Se recomienda continuar utilizando un método anticonceptivo eficaz y médicamente aceptable durante 30 días después de la finalización del estudio.
    12.Estar dispuesto y ser capaz de acudir a las visitas programadas y cumplir el plan de tratamiento, los análisis clínicos y otros procedimientos relacionados con el estudio para completar la participación en este.
    13.Ser capaz de comprender el documento de consentimiento y otorgar su consentimiento informado por escrito.
    14.El Comité de Validación de la Inclusión (CVI) debe aprobar al candidato como satisfactorio.
    E.4Principal exclusion criteria
    1. Atypical or secondary parkinsonism.
    2. Previous treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (s.c.) apomorphine infusion; subcutaneous (s.c.) apomorphine injection; Duodopa/Duopa; or APL-130277.
    3. Contraindications to domperidone, subcutaneous apomorphine, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of subcutaneous apomorphine (notably sodium metabisulfite).
    4. Female who is pregnant or lactating.
    5. Participation in a clinical trial within 30 days prior to SV1.
    6. Receipt of any investigational (ie, unapproved) medication within 30 days prior to SV1.
    7. Currently taking selective 5HT3 antagonists (ie, ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents. Subjects receiving anti-depressants must be on a stable daily dose for at least 8 weeks before SV1.
    8. The subject has a current diagnosis or history of substance abuse (excluding cannabinoids, nicotine, and caffeine) or alcohol abuse (in the opinion of the investigator) < 6 months prior to SV1.
    9. Subject has a history of malignancy within 5 years prior to SV1, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Pituitary tumors of any duration are excluded.
    10. Subject has a clinically significant abnormality on screening evaluation including physical examination, vital signs, ECG, or laboratory tests that the Investigator considers to be inappropriate to allow participation in the study.
    11. Subject has screening laboratory test results of: blood urea nitrogen (BUN) value ≥ 1.5 times the upper limit of normal (ULN) for the reference range; serum creatinine > 1.5 times the ULN for the reference range; or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥ 2 times the ULN for the reference laboratory.
    12. Subject is on injectable medication for the treatment of Type 2 diabetes. A subject with Type 2 diabetes is eligible for study inclusion if considered clinically stable, which is defined as
    • Random (non-fasting) screening glucose is < 200 mg/dl (11.1 mmol/L); and
    • HbA1c ≤ 6.5%; and
    • If a subject is currently being treated with oral anti-diabetic medication(s), the dose must have been stable for at least 4 weeks prior to screening. Such medication may be adjusted or discontinued during the study, as clinically indicated.
    Note: If the subject's random (non-fasting) screening glucose is ≥ 200 mg/dL (11.1 mmol/L), glucose must be retested in a fasted state. If the retested fasted value is ≥ 126 mg/dL (7.0 mmol/L), the subject will be excluded.
    13. The subject’s screening ECG at SV1 or SV2 shows a corrected QT interval using Fridericia’s formula (QTcF) of ≥ 450 msec for male subjects or ≥ 470 msec for female subjects. Eligibility will be based on the core laboratory ECG interpretation report.
    14. Subject has a positive screening laboratory test result for human immunodeficiency virus (HIV).
    15. Subject has a positive screening laboratory test result for hepatitis B surface antigen or hepatitis C antibodies and has liver function test results at screening above the ULN for the reference laboratory.
    16. Subject has major psychiatric disorder, including but not limited to in the last 12 months: bipolar disorder, psychosis (including hallucinations), major depressive episode, or any disorder that, in the opinion of the Investigator, requires new or ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
    17. Subject has Parkinson's disease psychosis (PDP) that precludes providing informed consent or would interfere with participation in the study. Symptoms of PDP commonly include visual hallucinations, delusions (paranoia) and illusions (misperception of objects).
    18. History of clinically significant impulse control disorder(s).
    19. Orthostatic hypotension (defined clinically as requiring medication).
    20. Dementia that precludes providing informed consent or would interfere with participation in the study.
    21. Current suicidal ideation within one year prior to Screening Visit 2 (SV2) as evidenced by answering "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.
    22. Presence of canker or mouth sores in the 30 days prior to SV1, or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a subject into the study.
    1.Parkinsonismo atípico o secundario.
    2.Alguno de los siguientes tratamientos previos: procedimiento neuroquirúrgico para la EP; infusión subcutánea (s.c.) continua de apomorfina, inyección subcutánea (s.c.) de apomorfina, duodopa/duopa o APL-130277
    3.Contraindicaciones para domperidona, apomorfina subcutánea o hipersensibilidad a la apomorfina clorhidrato o a cualquiera de los ingredientes de la apomorfina subcutánea (especialmente al metabisulfito sódico).
    4.Mujeres embarazadas o en periodo de lactancia.
    5.Participación en un ensayo clínico en un plazo de 30 días antes de la VS1.
    6.Tratamiento con cualquier fármaco experimental (es decir, no comercializado) en un plazo de 30 días antes de la VS1.
    7.Estar tomando actualmente antagonistas selectivos del 5HT3 (es decir, ondansetrón, granisetrón, dolasetrón, palonosetrón y alosetrón), antagonistas de la dopamina (a excepción de la quetiapina o la clozapina) o agentes reductores de la dopamina.Los sujetos en tratamiento con antidepresivos deben mantener una dosis diaria estable durante al menos 8 semanas antes de la VS1.
    8.El sujeto tiene un diagnóstico actual o antecedentes de toxicomanías (excluyendo los cannabinoides, la nicotina y la cafeína) o de alcoholismo (en opinión del investigador) <6 meses antes de la VS1.
    9.El sujeto tiene antecedentes de neoplasias malignas en los 5 años anteriores a la VS1, excepto en los casos de carcinoma basocelular, carcinoma espinocelular o cáncer de cuello uterino localizado tratados adecuadamente.Se excluyen los tumores en la pituitaria de cualquier duración.
    10.El sujeto tiene una anomalía clínicamente significativa en la evaluación de selección, incluidos exámenes físicos, constantes vitales, ECG o pruebas de laboratorio que el investigador considere inapropiadas para la participación en el estudio.
    11.Los resultados de las pruebas analíticas del sujeto en la selección son: valor del nitrógeno ureico en sangre (NUS) ≥ 1,5 veces el límite superior de la normalidad (LSN) para el intervalo de referencia; creatinina sérica > 1,5 veces el LSN para el intervalo de referencia; o valor de alanina aminotransferasa (ALT) o aspartato aminotransferasa (AST) ≥ 2 veces el LSN para el laboratorio de referencia.
    12.El sujeto recibe medicación inyectable para tratar la diabetes de tipo 2.Un sujeto con diabetes de tipo 2 puede participar en el estudio si se considera que está clínicamente estable, lo que se define como sigue:
    - La glucemia (sin ayunar) en la selección aleatoria es <200 mg/dl (11,1 mmol/l); y
    -HbA1c ≤ 6,5 %; y
    - Si un sujeto está recibiendo actualmente tratamiento con medicamentos antidiabéticos orales, la dosis debe haberse mantenido estable durante al menos 4 semanas antes de la selección.Dicha medicación podrá ajustarse o interrumpirse durante el estudio, en función del cuadro clínico.
    Nota:Si la glucemia (sin ayunar) del sujeto en la selección aleatoria es ≥200 mg/dl (11,1 mmol/l), deberá medirse la glucosa de nuevo en ayunas.Si el valor de la glucosa en ayunas es ≥126 mg/dl (7,0 mmol/l), el sujeto será excluido del estudio.
    13.El ECG del sujeto en la selección durante la VS1 o VS2 muestra un intervalo QT corregido usando el valor de la fórmula de Fridericia (QTcF) >450 ms en el caso de los sujetos varones o ≥470 ms en el caso de las mujeres.La elegibilidad se basará en el informe de interpretación del ECG del laboratorio central.
    14.El sujeto tiene un resultado positivo en las pruebas analíticas del virus de inmunodeficiencia humana (VIH).
    15.El sujeto tiene un resultado positivo en las pruebas analíticas del antígeno de superficie de la hepatitis B o los anticuerpos de hepatitis C y unos resultados en las pruebas de la función hepática en la selección por encima del LSN para el laboratorio de referencia.
    16.El sujeto sufre trastornos psiquiátricos importantes en los últimos 12 meses, como trastorno bipolar, psicosis (incluidas alucinaciones), episodio depresivo grave o cualquier otra afección que, en opinión del investigador, requiera un tratamiento nuevo o continuado, que haría que la participación en el estudio no fuera segura o dificultara el cumplimiento terapéutico.
    17.El sujeto tiene psicosis en la enfermedad de Parkinson (PEP) que le impida otorgar el consentimiento informado o interfiera con la participación en el estudio.Entre los síntomas de la PEP se incluyen normalmente alucinaciones, delirios (paranoia) y conceptos imaginarios (percepción errónea de objetos).
    18.Antecedentes de trastornos de control de los impulsos significativos desde el punto de vista clínico.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the percentage of subjects preferring APL-130277 over s.c. apomorphine. The overall subject preference will be based on
    preference of method of dose titration (PART A) and method of treatment (PART B). The subjects who prefer APL-130277 dose titration / treatment in
    both PART A and PART B will be defined as preferring APL-130277. The subjects who prefer s.c. apomorphine dose titration/treatment both in PART A and PART B will be defined as preferring s.c. apomorphine. For subjects who prefer different dose titration / treatment in PART A and PART B, the preference of PART B will be used for the primary endpoint. For subjects who only provide preference data from one of the two periods (PART A or PART B), the available preference will be used for the primary endpoint.
    El criterio principal de valoración es el porcentaje de sujetos que prefieren APL-130277 a la apomorfina s.c. La preferencia general de los sujetos se basará en la preferencia del método de ajuste de la dosis (PARTE A) y del método de tratamiento (PARTE B).Los sujetos que prefieran el ajuste de la dosis/el tratamiento con APL-130277 tanto en la PARTE A como en la PARTE B se definirán como aquellos que prefieren APL-130277.Los sujetos que prefieran el ajuste de la dosis/el tratamiento con apomorfina s.c. tanto en la PARTE A como en la PARTE B se definirán como aquellos que prefieren apomorfina s.c. En el caso de los sujetos que prefieran diferentes ajustes de la dosis/tratamientos en la PARTE A y la PARTE B, se empleará la preferencia de la PARTE B para el criterio principal de valoración.En el caso de los sujetos que solo proporcionen datos de preferencia para uno de los dos periodos (PARTE A o PARTE B), se empleará la preferencia disponible para el criterio principal de valoración.
    E.5.1.1Timepoint(s) of evaluation of this end point
    For PART A, Subject Preference question should be completed at the last titration visit once the subject has completed titration to both treatment regimens immediately prior to being scheduled for PART B. For PART B, Subject Preference question should be completed at V6
    Para la PART A, El Cuestionario de Preferencia de los Sujetos debe completarse en la última visita de ajuste de dosis una vez el sujeto haya terminado el ajuste de dosis de ambos regímenes de tratamientos inmediatamente antes de que se le programe para la PARTE B. Para la PARTE B, El Cuestionario de Preferencia de los Sujetos debe completarse en la V6.
    E.5.2Secondary end point(s)
    The key secondary endpoint (PART B) is the mean change from pre-dose in MDS-UPDRS Part III Motor Examination score at 90 minutes post-dose. The
    key secondary endpoint is evaluated at V3 and V6, after 4 weeks of dosing in each crossover period of PART B, and a blinded rater will be used for this
    assessment.
    The secondary endpoints are defined below for PART B. The secondary endpoints will be tested in a hierarchical manner in the order below after the
    primary and key secondary endpoints are tested.
    • MDS-UPDRS – Part II: Motor Aspects of Experiences of Daily Living: mean change from Screening in the MDS-UPDRS Part II sum score: this endpoint is evaluated at V3 and V6, after 4 weeks of dosing in each crossover period of PART B;
    • Patient Global Impression of Improvement (PGI): The percentage of subjects improved (ie, very much improved, much improved or minimally improved): this endpoint is evaluated at V3 and V6, after 4 weeks of dosing in each crossover period of PART B;
    •Percentage of subjects without a worsening amount of troublesome dyskinesia (ie, more than usual in the last month): this endpoint will be derived from the extra in-clinic question at V3 and V6, after 4 weeks of dosing in each crossover period of PART B;
    • Parkinson’s Disease Questionnaire-39 (PDQ-39) : mean change from Screening in Summary Index score: this endpoint is evaluated at V3 and V6, after 4 weeks of dosing in each crossover period of PART B;
    • Percentage of subjects with investigator confirmed Full “ON” within 30 minutes post-dose: this endpoint is evaluated at V3 and V6, after 4 weeks of dosing in each crossover period of PART B
    Other Endpoints - PART A
    • Subject preference as to method of dose titration;
    • Ease of Use: the proportion of subjects rating APL-130277 easier to use versus s.c. apomorphine;
    • Percentage of subjects with Investigator-rated full "ON" response within 30 minutes.
    Other Endpoints - PART B
    • Subject preference as to method of treatment;
    • Ease of Use: the proportion of subjects rating APL-130277 easier to use versus s.c. apomorphine;
    • Percentage of subjects experiencing "ON" episodes at 30 minutes post-dosing based on home dosing diary;
    • Number of times subjects took strip or injection during dosing days as recorded on home dosing diary;
    • Troublesome Dyskinesia as recorded on the home dosing diary;
    • MDS-UPDRS Part III: mean change from pre-dose to 90 minutes post-dose at V2 and V5;
    • MDS-UPDRS Part III: mean change from pre-dose to 30 and 60 minutes post-dose at V2, V3, V5, and V6;
    • MDS-UPDRS – Part I: mean change from Screening in the MDS-UPDRS Part I score at V2, V3, V5, and V6;
    • MDS-UPDRS – Part II: mean change from Screening in the MDS-UPDRS Part II sum score at V2 and V5;
    • MDS-UPDRS – Part IV: mean change from Screening in the MDS-UPDRS Part IV score at V2, V3, V5, and V6;
    • Clinician Global Impression of Improvement (CGI): The percentage of subjects improved (ie, very much improved, much improved or minimally improved) at V3 and V6;
    • Parkinson’s Disease Questionnaire-39 (PDQ-39): mean change from Screening in Summary Index score at V2 and V5;
    • Percentage of subjects with investigator confirmed Full “ON” within 30 minutes post-dose at V2 and V5;
    • European Quality of Life – 5 Dimensions (EQ-5D);
    • Time to full "ON" at V2, V3, V5, and V6;
    • Average total daily “OFF” time based on home dosing diary.
    Safety Endpoints - PART A and PART B
    • Evaluation of safety and tolerability as measured by AEs, physical examination including assessment of oropharyngeal AEs, 12-lead ECGs, vital signs including orthostatic hypotension (OH), clinical laboratory tests, and C-SSRS and QUIP-RS assessments;
    • Assessment of study drug administration site (oral and injection site examinations).
    Pharmacokinetic Endpoints – PART B
    Pharmacokinetic concentration-time data for apomorphine and metabolites (apomorphine sulfate and norapomorphine) will be evaluated. The following PK parameters will be estimated by noncompartmental methods from plasma samples using actual elapsed time from dosing. In addition, other PK parameters including apparent total clearance (CL/F) and apparent volume of distribution (V/F) will be calculated as appropriate.
    • Cmax: Maximum observed plasma concentration;
    • tmax: The observed time of the maximum concentration;
    • AUClast: Area under the concentration-time curve from time zero to the last measurable plasma concentration-time curve using the linear up log down trapezoidal rule;
    • AUC∞: Area under the concentration-time curve from time zero extrapolated to infinity using the linear up log down trapezoidal rule;
    • λz: Terminal-phase rate constant;
    • t½: Terminal-phase half-life;
    • MRT: Mean residence time;
    • M/P Ratio: Metabolite-to-parent ratio of Cmax and AUC.
    El criterio secundario clave de valoración (PARTE B) es la variación media respecto al momento previo a la administración en la puntuación de la parte III (exploración del sistema motor) de la escala MDS-UPDRS 90 minutos después de la administración.El criterio secundario clave de valoración se evalúa en la V3 y la V6, después de 4 semanas de administración en cada periodo con grupos cruzados de la PARTE B; esta evaluación la llevará a cabo un evaluador que desconozca el tratamiento.
    A continuación se definen los criterios secundarios de valoración para la PARTE B. Los criterios secundarios de valoración se probarán de forma jerárquica en el orden siguiente después de que se hayan probado los criterios de valoración primarios y secundarios clave.
    - MDS-UPDRS – Parte II:Aspectos motores de las experiencias de la vida cotidiana:cambio medio desde la selección en la suma de la puntuación de la parte II de MDS-UPDRS: este criterio de valoración se evalúa en la V3 y la V6, después de 4 semanas de administración en cada periodo con grupos cruzados de la PARTE B;
    - Impresión global de mejora del paciente (PGI-I):el porcentaje de sujetos que ha mejorado (es decir, mejorado mucho, mejorado bastante o mejorado mínimamente): este criterio de valoración se evalúa en la V3 y la V6, después de 4 semanas de administración en cada periodo con grupos cruzados de la PARTE B;
    - Porcentaje de sujetos sin empeoramiento de discinesia problemática (es decir, más de lo normal el último mes): este criterio de valoración derivará de la pregunta adicional en el centro en la V3 y la V6, después de 4 semanas de administración en cada periodo con grupos cruzados de la PARTE B;
    - Cuestionario de la enfermedad de Parkinson-39 (PDQ-39): cambio medio desde la selección en la suma de la puntuación del índice resumido: este criterio de valoración se evalúa en la V3 y la V6, después de 4 semanas de administración en cada periodo con grupos cruzados de la PARTE B;
    - Porcentaje de sujetos que presentan un estado «ON» completo confirmado por el investigador en los 30 minutos posteriores a la administración: este criterio de valoración se evalúa en la V3 y la V6, después de 4 semanas de administración en cada periodo con grupos cruzados de la PARTE B;
    Otros criterios de valoraciónPARTE A
    - Preferencia de los sujetos en cuanto al método de ajuste de dosis;
    - Facilidad de uso: la proporción de sujetos que opina que APL-130277 es más fácil de usar que la apomorfina s.c.;
    - Porcentaje de sujetos que presenten una respuesta «ON» completa según la valoración del investigador en un plazo de 30 minutos.
    Otros criterios de valoraciónPARTE B
    - Preferencia de los sujetos en cuanto al método de tratamiento;
    -Facilidad de uso: la proporción de sujetos que opina que APL-130277 es más fácil de usar que la apomorfina s.c.;
    - Porcentaje de sujetos que experimenten episodios «ON» 30 minutos después de la administración sobre la base del diario de administración en el domicilio.
    - Número de veces que los sujetos tomaron una tira o recibieron una inyección durante los días de administración según el registro del diario de administración en el domicilio.
    - Discinesia problemática según el registro en el diario de administración en el domicilio.
    - Parte III de MDS-UPDRS: cambio medio desde antes de la administración hasta 90 minutos después de la administración en la V2 y la V5;
    - Parte III de MDS-UPDRS: cambio medio desde antes de la administración hasta 30 y 60 minutos después de la administración en las V2, V3, V5 y V6;
    - MDS-UPDRS – Parte I: cambio medio desde la selección en la puntuación de la parte I de MDS UPDRS en las V2, V3, V5 y V6;
    - MDS-UPDRS – Parte II: cambio medio desde la selección en la puntuación de la parte II de MDS UPDRS en la V2 y la V5;
    - MDS-UPDRS – Parte IV: cambio medio desde la selección en la puntuación de la parte IV de MDS UPDRS en las V2, V3, V5 y V6;
    - Impresión global de mejora del médico (CGI):el porcentaje de sujetos que han mejorado (es decir, mejorado mucho, mejorado bastante o mejorado mínimamente) en la V3 y la V6;
    - Cuestionario de la enfermedad de Parkinson PDQ-39 (PDQ-39): cambio medio desde la selección en la puntuación del índice resumido en la V2 y la V5;
    - Porcentaje de sujetos que presentan un estado «ON» completo confirmado por el investigador en los 30 minutos posteriores a la administración en la V2 y la V5;
    - Cuestionario europeo de calidad de vida de cinco dimensiones (EQ5D);
    - Tiempo transcurrido hasta el estado «ON» completo en las V2, V3, V5 y V6;
    - Duración total media diaria en estado «OFF» según el diario de administración en el domicilio.
    Criterios de valoración de la seguridad PARTES A y B
    - Evaluación de la seguridad y la tolerabilidad en función de los AA, exploración física que incluirá la evaluación de AA orofaríngeos, ECG de 12 derivaciones, constantes vitales como la hipotensión ortostática (HO), análisis de laboratorio y evaluaciones de CSSRS y QUIP RS;
    E.5.2.1Timepoint(s) of evaluation of this end point
    Key 2ary Endpoint Part B mean change from pre to 90 min post-dose MDS-UPDRS Part III 2ary Endpoints P.B tested hierarchically, order below: MDS-UPDRS Part II; PGI; subjects % without worsening of troublesome dyskinesia; PDQ-39; subjects % with Full “ON” at 30 min Other Endpoints P.A: Titration Method Subject preference; Ease of Use; Subjects % with Full "ON" at 30 min. P.B Treatment Method Subject preference; Ease of Use; Subjects % experiencing "ON" episodes at 30 min; Strip intakes or injections; Troublesome Dyskinesia; MDS-UPDRS Part III, I, II, IV; CGI; PDQ-39; Subjects % with Full “ON”; EOQL, EQ 5D ; Time to Full "ON"; total daily “OFF” time Safety Endpoints P.A&B Safety & tolerability evaluation Pharmacokinetic Endpoints P.B apomorphine & metabolites concentration-time data
    Crite. 2 clave d val. P. B varia.media desde momen. previo- 90m tras la admin partIII d escala MDS-UPDRS .Criterio2d val. P.B;probada jerárquica.,:MDS-UPDRS, PartII; PGI-I; %d suje. sin empeora. d discinesia problema. ;PDQ-39, %d suje. con estado «ON» comple. en 30m.Otros crite.d val. P.A ;Prefer. de los suje. del método d ajuste ddosis-Facili. d uso:% d suj. con1estad «ON» comple. en 30m. P. B:Prefere. d los suje.del método d trata.;Facil.de uso: %d suje. q experi. episod «ON» los 30m. Tomad1 tira/inyección, discinesia problema., Part III,I,II,IV,PGI-I,PDQ-39. MDS-UPDRS;%d suje. con estado «ON» comple. EOQL,EQ-5D.T estado «ON» comple.,T. total media dia. estado «OFF» Crite. d val. d segu. P.A yB: Eval.d segu. y toler. Crite. de val.Farmacociné. P. B datos conc.-T.d la apomo. sus metabo.
    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 Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Ease of use and Tolerability
    Facilidad de uso y tolerabilidad
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    UVUS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months14
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months14
    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.1.2.1Number of subjects for this age range: 51
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 34
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 85
    F.4.2.2In the whole clinical trial 85
    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)
    None
    Ninguno
    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 Decision2018-02-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-24
    P. End of Trial
    P.End of Trial StatusOngoing
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