A Study to Assess the Safety and Efficacy of the of the Gastric-retentive AP-CD/LD in Advanced Parkinson's Patients

NCT02605434 | Unknown Phase 3 DMC

• 1 other identifier: IN 11 004
• Study Type: interventional
• Target: 420
• Locations: 10 countries
• Sites: 97

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Fluctuating Parkinson's Disease; Advanced Parkinson's Disease; Carbidopa; Levodopa; Accordion; Accordance

Outcome Measures

Primary Outcomes (1)

• Change from Baseline through study completion, an average of 27 weeks, in the percentage of daily "Off time" during waking hours

  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.

  Baseline through study completion, an average of 27 weeks

Secondary Outcomes (4)

• 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

• 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 total UPDRS Score (Sum of Parts I-III)

  Baseline through study completion, an average of 27 weeks

Study Arms (2)

AP-CD/LD

EXPERIMENTAL

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

Drug: Accordion Pill™ Carbidopa/Levodopa; Drug: Placebo -AP-CD/LD

SINEMET®

ACTIVE COMPARATOR

IR Carbidopa/ levodopa tablets 25/100 mg at least 4 times a day and placebo AP-CD/LD

Drug: Sinemet®; Drug: Placebo- Sinemet

Interventions

Accordion Pill™ Carbidopa/Levodopa DRUG

AP-CD/LD capsule containing 50 mg carbidopa with 400 mg or 500 mg levodopa administered orally twice or 3 times a day

Also known as: AP-CD/LD

AP-CD/LD

Sinemet® DRUG

Sinemet® tables containing carbidopa and levodopa 25/100 mg will be administered orally at least 4 times a day according to patients need

Also known as: IR Carbidopa/Levodopa

SINEMET®

Placebo -AP-CD/LD DRUG

Placebo for AP-CD/LD capsule

AP-CD/LD

Placebo- Sinemet DRUG

Placebo for Sinemet tables

SINEMET®

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Intec Pharma Ltd.: lead

Study Sites (97)

University Alabama Hospital Neurology

Birmingham, Alabama, 35233, United States

Location

Saint Joseph's Hospital and Medical Center Muhammad Ali Parkinson Research Center

Phoenix, Arizona, 85013, United States

Location

Parkinson's Disease & Movement Disorders Center, Dept of Neu

Fountain Valley, California, 92708, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

SC3 Research

Pasadena, California, 91105, United States

Location

SC3 Research

Reseda, California, 91335, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Colorado Dept. of Neurology

Aurora, Colorado, 80045, United States

Location

Hartford HealthCare

Vernon, Connecticut, 06066, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Collier Neurologic Specialists, LLC

Naples, Florida, 34102, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Parkinson's Disease and Movement Disorders Center

Tampa, Florida, 33613, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

The University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Henry Ford Hospital

West Bloomfield, Michigan, 48322, United States

Location

Dartmouth Hitchcock Neurology

Lebanon, New Hampshire, 03756, United States

Location

Atlantic Health System Hospital Corp.-Overlook Hospital

Summit, New Jersey, 07902, United States

Location

David L. Kreitzman, MD., PC

Commack, New York, 11725, United States

Location

Fresco Institute for Parkinson's and Movement Disorders

New York, New York, 10016, United States

Location

Weill Cornell Medical College of Cornell University

New York, New York, 10021, United States

Location

Asheville Neurology Specialists

Asheville, North Carolina, 28806, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0525, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

Vanderbilt University Medical Center Vanderbilt Clinical Neurosciences

Nashville, Tennessee, 37232, United States

Location

North Texas Movement Disorders Institute

Bedford, Texas, 76021, United States

Location

Baylor College of Medicine Department of Neurology

Houston, Texas, 77030, United States

Location

Charlottesville Medical Research

Charlottesville, Virginia, 22911, United States

Location

Booth Garner Parkinson's Care Center

Kirkland, Washington, 98034, United States

Location

MHAT 'Sv.Pantaleymon - Pleven' OOD

Pleven, 5800, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD

Plovdiv, 4002, Bulgaria

Location

Clinic for Neurology and Sleep Medicine

Sofia, 1407, Bulgaria

Location

Clinic of Neurological Diseases

Sofia, 1797, Bulgaria

Location

Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD

Varna, 9010, Bulgaria

Location

Neuroakademie Alzenau GbR

Aschaffenburg, 63755, Germany

Location

Praxis für Neurologie und Psychiatrie

Berlin, 12163, Germany

Location

Uniklinikum Carl-Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Technischen Universitaet Muenchen (TUM) - Klinikum Rechts der Isar

München, 81675, Germany

Location

Praxis für Neurologie und Psychiatrie

Westerstede, 26655, Germany

Location

Rambam Medical Center

Haifa, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center at Tel Hashomer

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Ospedale Generale Regionale Francesco Miulli

Acquaviva delle Fonti, 70021, Italy

Location

Ospedali Riuniti di Ancona

Ancona, 60126, Italy

Location

Spedali Civili Di Brescia Azienda Ospedaliera

Brescia, 25123, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

Location

IRCCS Neurologico Fondazione "C. Mondino"

Pavia, 27100, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, 56126, Italy

Location

IRCCS San Raffaele Pisana

Roma, 00163, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Azienda Ospedaliera Universitaria San Giovanni di Dio Ruggi d'Aragona

Salerno, 84131, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

Azienda Unitá Locale Socio Sanitaria 12 Veneziana - Ospedale dell'Angelo

Venezia, 30174, Italy

Location

Casa di Cura Villa Margherita

Vicenza, 36057, Italy

Location

Centrum Medyczne Damiana Holding

Warsaw, Masovian Voivodeship, 02-777, Poland

Location

VITAMED Galaj i Cichomski spólka jawna

Bydgoszcz, 85-021, Poland

Location

Anna Kapustecka Prywatna Przychodnia Specjalistyczna STOMED

Częstochowa, 42-280, Poland

Location

NEURO-CARE Site Management Organization Gabriela Klodowska-Duda

Katowice, 40-749, Poland

Location

Centrum Medyczne Pratia Katowice I

Katowice, 40-954, Poland

Location

Krakowska Akademia Neurologii Sp. z o. o.

Krakow, 31-505, Poland

Location

Gabinet Lekarski Prof. Andrzej Bogucki

Lodz, 90-130, Poland

Location

Centrum Medyczne Pratia Warszawa

Warsaw, 01-868, Poland

Location

Neurologicka ambulancia, Euro-Neuro s.r.o.

Bratislava, 83103, Slovakia

Location

KONZÍLIUM s.r.o.

Považská Bystrica, 01726, Slovakia

Location

NEURON - D.T. s.r.o.

Žilina, 01001, Slovakia

Location

HM Puerta del Sur

Móstoles, Madrid, 28938, Spain

Location

Hospital Universitari Quirón Dexeus

Barcelona, 08028, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario La Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Hospital Puerta de Hierro Majadahonda

Majadahonda, 28222, Spain

Location

Hospital Infanta Sofía

San Sebastián de los Reyes, 28702, Spain

Location

Hospital General de Cataluña

Sant Cugat del Vallès, 08195, Spain

Location

Ukrainian State Scientific Research Institution of Medical and Social Problems of Disability

Cherkasy, 18009, Ukraine

Location

Dnipropetrovsk medical academy MOH of Ukraine

Dnipro, Ukraine

Location

Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine

Kharkiv, 61068, Ukraine

Location

State Institution "Institute of Gerontology of the AMS of Ukraine"

Kyiv, 04114, Ukraine

Location

Lviv City Clinical Hospital

Lviv, 79010, Ukraine

Location

Regional Clinical Hospital n.a. N.V. Sklifosovskyi

Poltava, 36024, Ukraine

Location

Municipal Institution "Zaporizhzhya City Clinical Multidisciplinary Hospital #9"

Zaporizhzhya, 69035, Ukraine

Location

Municipal Institution 6¿ City Clinical Hospital

Zaporizhzhya, 69035, Ukraine

Location

Clinical Hospital #2

Zaporozh’ye, 69600, Ukraine

Location

Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council

Zaporozh’ye, 69600, Ukraine

Location

Fairfield General Hospital

Bury, BL9 7TD, United Kingdom

Location

Newcastle University Clinical Ageing Research

Newcastle upon Tyne, NE4 5PL, United Kingdom

Location

Queens Medical Centre Nottingham, University Hospital

Nottingham, NG7 2UH, United Kingdom

Location

University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31127735 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

Levodopa; carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Peter A LeWitt, MD

  Henry Ford Hospital - West Bloomfield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 16, 2015
• Study Start: March 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 8, 2019

Record last verified: 2018-04

Locations

DE (5); BU (5); IT (12); SL (3); ES (10); PL (8); GB (4); IL (4); US (36); UA (10)