A Study to Assess the Safety and Efficacy of the of the Gastric-retentive AP-CD/LD in Advanced Parkinson's Patients
- Conditions
- Parkinson's Disease
- Interventions
- Registration Number
- NCT02605434
- Lead Sponsor
- Intec Pharma Ltd.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 420
-
Subjects must be approved for suitability by an Enrollment Approval Committee
-
Able and willing to give written (signed and dated) informed consent and adhere to visit schedule and available to complete the study
-
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)
-
Diagnosed with Parkinson's disease, consistent with UK brain bank criteria
-
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
-
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
-
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.
-
Able to complete a Hauser Home Diary and can tell the difference between "On" and "Off" time
- Achieved at least 75% diary concordance with an approved site rater in a 4-hour training session including at least one "Off time" assessment
- Returned a valid 2-day practice diary after training has been completed.
-
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).
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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.
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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
- Participation in another drug clinical trial within 28 days prior to initial screening assessment (calculated from the previous study's last dosing date)
- 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)
- 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.
- Severe dyskinesia in the opinion of either the investigator or the Enrollment Approval Committee.
- 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
- Previous or planned neurosurgical treatment for Parkinson's Disease (e.g., procedures including ablation or deep brain stimulation) during the course of the study
- Significant cognitive impairment as defined by the Mini-Mental State Examination (MMSE) score < 26.
- 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)
- 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)
- Currently experiencing or any known history of psychosis or delusions within 2 years prior to Screening.
- Known history of substance abuse within the past 2 years
- Moderate or greater level of alcohol consumption
- Unable to swallow large pills (e.g., large vitamin pills)
- History of Melanoma or suspicious skin lesion which could be a Melanoma
- Narrow-angle Glaucoma
- 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).
- Active peptic ulcer disease or a history of peptic ulcer or upper GI bleeding
- Regular use of opioids (Intermittent opioid use is not exclusionary)
- Symptomatic gastroparesis with frequent vomiting (at least once a week)
- Concomitant use of NSAIDs and oral steroids within the past 28 days
- Allergy to the study drug or any of its excipients, or to Yellow Dye #5 (tartrazine)
- Women who are pregnant or nursing. Women of childbearing potential who are not willing to use a medically acceptable method of contraception.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SINEMET® Sinemet® IR Carbidopa/ levodopa tablets 25/100 mg at least 4 times a day and placebo AP-CD/LD AP-CD/LD Accordion Pill™ Carbidopa/Levodopa Accordion Pill™ Carbidopa/Levodopa Capsule 50/400mg , b.i.d or t.i.d or Accordion Pill™ Carbidopa/Levodopa Capsule 50/500mg , b.i.d or t.i.d and Placebo IR Carbidopa/ levodopa SINEMET® Placebo- Sinemet IR Carbidopa/ levodopa tablets 25/100 mg at least 4 times a day and placebo AP-CD/LD AP-CD/LD Placebo -AP-CD/LD Accordion Pill™ Carbidopa/Levodopa Capsule 50/400mg , b.i.d or t.i.d or Accordion Pill™ Carbidopa/Levodopa Capsule 50/500mg , b.i.d or t.i.d and Placebo IR Carbidopa/ levodopa
- Primary Outcome Measures
Name Time Method Change from Baseline through study completion, an average of 27 weeks, in the percentage of daily "Off time" during waking hours Baseline through study completion, an average of 27 weeks Change from Baseline through study completion, an average of 27 weeks, in the percentage of daily "Off time" during waking hours based on Hauser Home Diary assessments; Total number of "Off " hours normalized to a 16- hour waking day will also be calculated but only a single p-value applicable to both the percentage and hours will be reported.
- Secondary Outcome Measures
Name Time Method Change from Baseline through study completion, an average of 27 weeks, in total UPDRS Score (Sum of Parts I-III) Baseline through study completion, an average of 27 weeks Change in the number of total daily LD doses from Baseline through study completion, an average of 27 weeks (hours) Baseline through study completion, an average of 27 weeks CGI-I through study completion, an average of 27 weeks, as recorded by physician & patient Baseline through through study completion, an average of 27 weeks, Change from Baseline through study completion, an average of 27 weeks, in "On time" without troublesome dyskinesia during waking hours Baseline through study completion, an average of 27 weeks
Trial Locations
- Locations (95)
Praxis für Neurologie und Psychiatrie
🇩🇪Westerstede, Germany
Charlottesville Medical Research
🇺🇸Charlottesville, Virginia, United States
Fairfield General Hospital
🇬🇧Bury, United Kingdom
SC3 Research
🇺🇸Reseda, California, United States
Collier Neurologic Specialists, LLC
🇺🇸Naples, Florida, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
🇺🇸Boca Raton, Florida, United States
Henry Ford Hospital
🇺🇸West Bloomfield, Michigan, United States
Hospital Ruber Internacional
🇪🇸Madrid, Spain
Quest Research Institute
🇺🇸Farmington Hills, Michigan, United States
Newcastle University Clinical Ageing Research
🇬🇧Newcastle upon Tyne, United Kingdom
Hospital Universitari Quirón Dexeus
🇪🇸Barcelona, Spain
HM Puerta del Sur
🇪🇸Mostoles, Madrid, Spain
Uniklinikum Carl-Gustav Carus an der TU Dresden
🇩🇪Dresden, Germany
Fresco Institute for Parkinson's and Movement Disorders
🇺🇸New York, New York, United States
The Movement Disorder Clinic of Oklahoma
🇺🇸Tulsa, Oklahoma, United States
Hospital Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Clinic of Neurological Diseases
🇧🇬Sofia, Bulgaria
Chaim Sheba Medical Center at Tel Hashomer
🇮🇱Ramat Gan, Israel
Centrum Medyczne Pratia Katowice I
🇵🇱Katowice, Poland
Hospital Universitari Vall D'Hebron
🇪🇸Barcelona, Spain
Weill Cornell Medical College of Cornell University
🇺🇸New York, New York, United States
Spedali Civili Di Brescia Azienda Ospedaliera
🇮🇹Brescia, Italy
Neuroakademie Alzenau GbR
🇩🇪Aschaffenburg, Germany
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Rambam Medical Center
🇮🇱Haifa, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Technischen Universitaet Muenchen (TUM) - Klinikum Rechts der Isar
🇩🇪Munchen, Germany
Hospital General de Cataluña
🇪🇸Sant Cugat del Valles, Spain
Krakowska Akademia Neurologii Sp. z o. o.
🇵🇱Krakow, Poland
IRCCS Neurologico Fondazione "C. Mondino"
🇮🇹Pavia, Italy
Queens Medical Centre Nottingham, University Hospital
🇬🇧Nottingham, United Kingdom
Hospital Universitario La Princesa
🇪🇸Madrid, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
University Hospitals of North Midlands NHS Trust
🇬🇧Stoke-on-Trent, United Kingdom
Regional Clinical Hospital n.a. N.V. Sklifosovskyi
🇺🇦Poltava, Ukraine
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Boston University School of Medicine
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine Department of Neurology
🇺🇸Houston, Texas, United States
The University of Kansas Hospital
🇺🇸Kansas City, Kansas, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Ospedale Generale Regionale Francesco Miulli
🇮🇹Acquaviva delle Fonti, Italy
Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Italy
Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
IRCCS San Raffaele Pisana
🇮🇹Roma, Italy
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria San Giovanni di Dio Ruggi d'Aragona
🇮🇹Salerno, Italy
Azienda Unitá Locale Socio Sanitaria 12 Veneziana - Ospedale dell'Angelo
🇮🇹Venezia, Italy
Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Casa di Cura Villa Margherita
🇮🇹Vicenza, Italy
Saint Joseph's Hospital and Medical Center Muhammad Ali Parkinson Research Center
🇺🇸Phoenix, Arizona, United States
Parkinson's Disease & Movement Disorders Center, Dept of Neu
🇺🇸Fountain Valley, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Centrum Medyczne Damiana Holding
🇵🇱Warszawa, Mazowieckie, Poland
Ukrainian State Scientific Research Institution of Medical and Social Problems of Disability
🇺🇦Cherkasy, Ukraine
Hartford HealthCare
🇺🇸Vernon, Connecticut, United States
MHAT 'Sv.Pantaleymon - Pleven' OOD
🇧🇬Pleven, Bulgaria
University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD
🇧🇬Plovdiv, Bulgaria
Clinic for Neurology and Sleep Medicine
🇧🇬Sofia, Bulgaria
Atlantic Health System Hospital Corp.-Overlook Hospital
🇺🇸Summit, New Jersey, United States
Gabinet Lekarski Prof. Andrzej Bogucki
🇵🇱Lodz, Poland
Michigan State University
🇺🇸East Lansing, Michigan, United States
Rabin Medical Center
🇮🇱Petah Tiqva, Israel
KONZÍLIUM s.r.o.
🇸🇰Považská Bystrica, Slovakia
Municipal Institution "Zaporizhzhya City Clinical Multidisciplinary Hospital #9"
🇺🇦Zaporizhzhya, Ukraine
Vanderbilt University Medical Center Vanderbilt Clinical Neurosciences
🇺🇸Nashville, Tennessee, United States
Dartmouth Hitchcock Neurology
🇺🇸Lebanon, New Hampshire, United States
VITAMED Galaj i Cichomski spólka jawna
🇵🇱Bydgoszcz, Poland
NEURON - D.T. s.r.o.
🇸🇰Zilina, Slovakia
Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD
🇧🇬Varna, Bulgaria
Anna Kapustecka Prywatna Przychodnia Specjalistyczna STOMED
🇵🇱Czestochowa, Poland
NEURO-CARE Site Management Organization Gabriela Klodowska-Duda
🇵🇱Katowice, Poland
Centrum Medyczne Pratia Warszawa
🇵🇱Warszawa, Poland
Neurologicka ambulancia, Euro-Neuro s.r.o.
🇸🇰Bratislava, Slovakia
Lviv City Clinical Hospital
🇺🇦L'viv, Ukraine
Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
🇺🇦Zaporozh'ye, Ukraine
Dnipropetrovsk medical academy MOH of Ukraine
🇺🇦Dnipropetrovs'k, Ukraine
Clinical Hospital #2
🇺🇦Zaporozh'ye, Ukraine
Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
🇺🇦Kharkiv, Ukraine
State Institution "Institute of Gerontology of the AMS of Ukraine"
🇺🇦Kyiv, Ukraine
Municipal Institution 6¿ City Clinical Hospital
🇺🇦Zaporizhzhya, Ukraine
Hospital Infanta Sofía
🇪🇸San Sebastian de los Reyes, Spain
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
David L. Kreitzman, MD., PC
🇺🇸Commack, New York, United States
Asheville Neurology Specialists
🇺🇸Asheville, North Carolina, United States
Booth Garner Parkinson's Care Center
🇺🇸Kirkland, Washington, United States
University Alabama Hospital Neurology
🇺🇸Birmingham, Alabama, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
University of Colorado Dept. of Neurology
🇺🇸Aurora, Colorado, United States
Bioclinica Research
🇺🇸Orlando, Florida, United States
Parkinson's Disease and Movement Disorders Center
🇺🇸Tampa, Florida, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
North Texas Movement Disorders Institute
🇺🇸Bedford, Texas, United States
University of Toledo
🇺🇸Toledo, Ohio, United States