Clinical trial NCT02605434: A Study to Assess the Safety and Efficacy of the of the Gastric-retentive AP-CD/LD in Advanced Parkinson's Patients
Official title: Phase 3 Multicenter Randomized Double-Blind, Double-dummy, Active-Controlled Study Comparing Efficacy/Safety of Gastric-retentive, Controlled-release Accordion Pill Carbidopa/Levodopa to Immediate Release in Fluctuating Parkinson's Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
Fluctuating Parkinson's Disease
Advanced Parkinson's Disease
Carbidopa
Levodopa
Accordion
Accordance
Lead sponsor: Intec Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2015-11-16
Enrollment: 420
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the gastric retentive Accordion Pill™ Carbidopa/Levodopa (AP-CD/LD) is more effective than the commercially available immediate release Carbidopa/Levodopa in reducing motor fluctuations such as "off time" in advanced Parkinson's Disease patients.

Detailed description: A multi-center, global, randomized, double-blind, double-dummy, active-controlled, parallel-group study in adult subjects with fluctuating PD. The study will have 2 open label Titration periods of 6 weeks each prior to the double blind Maintenance period. In the open label periods all patients will be stabilized on the active comparator Sinemet® and then on AP-CD/LD. The double blind Maintenance period will be 13 weeks long.

Eligibility criteria: Main Inclusion Criteria:

1. Subjects must be approved for suitability by an Enrollment Approval Committee
2. Able and willing to give written (signed and dated) informed consent and adhere to visit schedule and available to complete the study
3. Men or women 30 years of age and higher at initial screening assessment. (For the 100 subjects who enter the Gastroscopy sub study, the age limits are 30-80 years of age, inclusive, at initial screening assessment)
4. Diagnosed with Parkinson's disease, consistent with UK brain bank criteria
5. Has a good response to Levodopa and is taking at least 4 doses of a Levodopa containing medication (or 3 doses of Rytary) per day during waking hours (not including nighttime long acting levodopa) at a stable dose for at least 28 days prior to initial screening assessment
6. Other Anti-PD treatment (such as dopamine agonists, selective MAO-B inhibitors, anticholinergic agents or Amantadine) are permitted if stable for at least 28 days prior to study entry and provided they are not anticipated to be changed during the course of the study
7. Total LD immediate release daily dose of 400 mg to 1300 mg or equivalent prior to initial screening assessment. Specifically for Rytary, doses up to 1755 mg daily are acceptable.
8. Able to complete a Hauser Home Diary and can tell the difference between "On" and "Off" time

   1. Achieved at least 75% diary concordance with an approved site rater in a 4-hour training session including at least one "Off time" assessment
   2. Returned a valid 2-day practice diary after training has been completed.
9. At least 2.5 hours "Off time" per day during waking hours on Screening 2-day Practice Hauser Home Diary (morning akinesia should be incorporated into the total "Off time" assessment).
10. Other than PD, the subject is in satisfactory health, as assessed by physical examination and screening tests. No clinically significant medical, psychiatric or laboratory abnormality that could compromise safety or interfere with study procedures in the opinion of either the investigator or the Enrollment Approval Committee/Sponsor.
11. Living in an area that is within 3 hours driving distance from the study site or is willing to stay in such a place the night before each study visit

Main Exclusion Criteria:

1. Participation in another drug clinical trial within 28 days prior to initial screening assessment (calculated from the previous study's last dosing date)
2. Atypical Parkinsonism (subjects with Parkinsonian features caused by disorder such as multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies or multiple brain infarcts)
3. Clinically significant cardiac, pulmonary, hepatic or renal disease or other condition or any major complication/illness which contraindicates his/her participation in the opinion of either the investigator or the Enrollment Approval Committee/Sponsor.
4. Severe dyskinesia in the opinion of either the investigator or the Enrollment Approval Committee.
5. Treatment with non-selective monoamine oxidase (MAO) inhibitors during the last 28 days prior to initial screening assessment or planning to take during study participation
6. Previous or planned neurosurgical treatment for Parkinson's Disease (e.g., procedures including ablation or deep brain stimulation) during the course of the study
7. Significant cognitive impairment as defined by the Mini-Mental State Examination (MMSE) score \< 26.
8. Clinically significant psychiatric illness, including major depression (Hamilton Depression Rating Scale-17 ≥14). Subjects with a lifetime history of suicidal attempt (including an active attempt, interrupted attempt or aborted attempt)
9. Current or previous treatment for more than 1 month within the past 2 years with any neuroleptic drug (antipsychotic) or any other drug with anti-dopaminergic properties (e.g. metoclopramide, domperidone)
10. Currently experiencing or any known history of psychosis or delusions within 2 years prior to Screening.
11. Known history of substance abuse within the past 2 years
12. Moderate or greater level of alcohol consumption
13. Unable to swallow large pills (e.g., large vitamin pills)
14. History of Melanoma or suspicious skin lesion which could be a Melanoma
15. Narrow-angle Glaucoma
16. History of small bowel or gastric surgery (Including PEG-J placement for Duopa/Duodopa) or bowel obstruction, diagnosis of small bowel narrowing, diagnosis of Crohn's disease, or frequent nausea or emesis, regardless of etiology, (Previous appendectomy or hernioplasty will not be exclusionary).
17. Active peptic ulcer disease or a history of peptic ulcer or upper GI bleeding
18. Regular use of opioids (Intermittent opioid use is not exclusionary)
19. Symptomatic gastroparesis with frequent vomiting (at least once a week)
20. Concomitant use of NSAIDs and oral steroids within the past 28 days
21. Allergy to the study drug or any of its excipients, or to Yellow Dye #5 (tartrazine)
22. Women who are pregnant or nursing. Women of childbearing potential who are not willing to use a medically acceptable method of contraception.

Primary outcomes:
measure: Change from Baseline through study completion, an average of 27 weeks, in the percentage of daily "Off time" during waking hours
timeFrame: Baseline through study completion, an average of 27 weeks
Secondary outcomes:
measure: Change from Baseline through study completion, an average of 27 weeks, in "On time" without troublesome dyskinesia during waking hours
timeFrame: Baseline through study completion, an average of 27 weeks
measure: Change in the number of total daily LD doses from Baseline through study completion, an average of 27 weeks (hours)
timeFrame: Baseline through study completion, an average of 27 weeks
measure: CGI-I through study completion, an average of 27 weeks, as recorded by physician & patient
timeFrame: Baseline through through study completion, an average of 27 weeks,
measure: Change from Baseline through study completion, an average of 27 weeks, in total UPDRS Score (Sum of Parts I-III)
timeFrame: Baseline through study completion, an average of 27 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Alabama Hospital Neurology
state: Alabama
city: Phoenix
country: United States
facility: Saint Joseph's Hospital and Medical Center Muhammad Ali Parkinson Research Center
state: Arizona
city: Fountain Valley
country: United States
facility: Parkinson's Disease & Movement Disorders Center, Dept of Neu
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Pasadena
country: United States
facility: SC3 Research
state: California
city: Reseda
country: United States
facility: SC3 Research
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Dept. of Neurology
state: Colorado
city: Vernon
country: United States
facility: Hartford HealthCare
state: Connecticut
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Naples
country: United States
facility: Collier Neurologic Specialists, LLC
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Tampa
country: United States
facility: Parkinson's Disease and Movement Disorders Center
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Neurology
state: New Hampshire
city: Summit
country: United States
facility: Atlantic Health System Hospital Corp.-Overlook Hospital
state: New Jersey
city: Commack
country: United States
facility: David L. Kreitzman, MD., PC
state: New York
city: New York
country: United States
facility: Fresco Institute for Parkinson's and Movement Disorders
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College of Cornell University
state: New York
city: Asheville
country: United States
facility: Asheville Neurology Specialists
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center Vanderbilt Clinical Neurosciences
state: Tennessee
city: Bedford
country: United States
facility: North Texas Movement Disorders Institute
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Department of Neurology
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research
state: Virginia
city: Kirkland
country: United States
facility: Booth Garner Parkinson's Care Center
state: Washington
city: Pleven
country: Bulgaria
facility: MHAT 'Sv.Pantaleymon - Pleven' OOD
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD
city: Sofia
country: Bulgaria
facility: Clinic for Neurology and Sleep Medicine
city: Sofia
country: Bulgaria
facility: Clinic of Neurological Diseases
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD
city: Aschaffenburg
country: Germany
facility: Neuroakademie Alzenau GbR
city: Berlin
country: Germany
facility: Praxis für Neurologie und Psychiatrie
city: Dresden
country: Germany
facility: Uniklinikum Carl-Gustav Carus an der TU Dresden
city: Munchen
country: Germany
facility: Technischen Universitaet Muenchen (TUM) - Klinikum Rechts der Isar
city: Westerstede
country: Germany
facility: Praxis für Neurologie und Psychiatrie
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petah Tiqva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center at Tel Hashomer
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Acquaviva delle Fonti
country: Italy
facility: Ospedale Generale Regionale Francesco Miulli
city: Ancona
country: Italy
facility: Ospedali Riuniti di Ancona
city: Brescia
country: Italy
facility: Spedali Civili Di Brescia Azienda Ospedaliera
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Pavia
country: Italy
facility: IRCCS Neurologico Fondazione "C. Mondino"
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria San Giovanni di Dio Ruggi d'Aragona
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Venezia
country: Italy
facility: Azienda Unitá Locale Socio Sanitaria 12 Veneziana - Ospedale dell'Angelo
city: Vicenza
country: Italy
facility: Casa di Cura Villa Margherita
city: Warszawa
country: Poland
facility: Centrum Medyczne Damiana Holding
state: Mazowieckie
city: Bydgoszcz
country: Poland
facility: VITAMED Galaj i Cichomski spólka jawna
city: Czestochowa
country: Poland
facility: Anna Kapustecka Prywatna Przychodnia Specjalistyczna STOMED
city: Katowice
country: Poland
facility: NEURO-CARE Site Management Organization Gabriela Klodowska-Duda
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice I
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Sp. z o. o.
city: Lodz
country: Poland
facility: Gabinet Lekarski Prof. Andrzej Bogucki
city: Warszawa
country: Poland
facility: Centrum Medyczne Pratia Warszawa
city: Bratislava
country: Slovakia
facility: Neurologicka ambulancia, Euro-Neuro s.r.o.
city: Považská Bystrica
country: Slovakia
facility: KONZÍLIUM s.r.o.
city: Zilina
country: Slovakia
facility: NEURON - D.T. s.r.o.
city: Mostoles
country: Spain
facility: HM Puerta del Sur
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Quirón Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
city: San Sebastian de los Reyes
country: Spain
facility: Hospital Infanta Sofía
city: Sant Cugat del Valles
country: Spain
facility: Hospital General de Cataluña
city: Cherkasy
country: Ukraine
facility: Ukrainian State Scientific Research Institution of Medical and Social Problems of Disability
city: Dnipropetrovs'k
country: Ukraine
facility: Dnipropetrovsk medical academy MOH of Ukraine
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
city: Kyiv
country: Ukraine
facility: State Institution "Institute of Gerontology of the AMS of Ukraine"
city: L'viv
country: Ukraine
facility: Lviv City Clinical Hospital
city: Poltava
country: Ukraine
facility: Regional Clinical Hospital n.a. N.V. Sklifosovskyi
city: Zaporizhzhya
country: Ukraine
facility: Municipal Institution "Zaporizhzhya City Clinical Multidisciplinary Hospital #9"
city: Zaporizhzhya
country: Ukraine
facility: Municipal Institution 6¿ City Clinical Hospital
city: Zaporozh'ye
country: Ukraine
facility: Clinical Hospital #2
city: Zaporozh'ye
country: Ukraine
facility: Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
city: Bury
country: United Kingdom
facility: Fairfield General Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University Clinical Ageing Research
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre Nottingham, University Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospitals of North Midlands NHS Trust
Study officials:
affiliation: Henry Ford Hospital - West Bloomfield
name: Peter A LeWitt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McFarthing K, Prakash N, Simuni T. CLINICAL TRIAL HIGHLIGHTS: 1. GENE THERAPY FOR PARKINSON'S, 2. PHASE 3 STUDY IN FOCUS - INTEC PHARMA'S ACCORDION PILL, 3. CLINICAL TRIALS RESOURCES. J Parkinsons Dis. 2019;9(2):251-264. doi: 10.3233/JPD-199001. No abstract available.