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

Parkinson's Disease Clinical Trial

— Accordance  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02605434
• Other study ID #: IN 11 004
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 2016
• Est. completion date: December 2019

Study information

• Verified date: April 2018
• Source: Intec Pharma Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 420
• Est. completion date: December 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Accordion Pill™ Carbidopa/Levodopa
AP-CD/LD capsule containing 50 mg carbidopa with 400 mg or 500 mg levodopa administered orally twice or 3 times a day
• Sinemet®
Sinemet® tables containing carbidopa and levodopa 25/100 mg will be administered orally at least 4 times a day according to patients need
• Placebo -AP-CD/LD
Placebo for AP-CD/LD capsule
• Placebo- Sinemet
Placebo for Sinemet tables

Locations

Country	Name	City	State
Bulgaria	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	Clinic of Neurological Diseases	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment "Sveta Marina'' EAD	Varna
Germany	Neuroakademie Alzenau GbR	Aschaffenburg
Germany	Praxis für Neurologie und Psychiatrie	Berlin
Germany	Uniklinikum Carl-Gustav Carus an der TU Dresden	Dresden
Germany	Technischen Universitaet Muenchen (TUM) - Klinikum Rechts der Isar	Munchen
Germany	Praxis für Neurologie und Psychiatrie	Westerstede
Israel	Rambam Medical Center	Haifa
Israel	Rabin Medical Center	Petah Tiqva
Israel	Chaim Sheba Medical Center at Tel Hashomer	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Ospedale Generale Regionale Francesco Miulli	Acquaviva delle Fonti
Italy	Ospedali Riuniti di Ancona	Ancona
Italy	Spedali Civili Di Brescia Azienda Ospedaliera	Brescia
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	IRCCS Neurologico Fondazione "C. Mondino"	Pavia
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	IRCCS San Raffaele Pisana	Roma
Italy	Azienda Ospedaliera Universitaria San Giovanni di Dio Ruggi d'Aragona	Salerno
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Italy	Azienda Unitá Locale Socio Sanitaria 12 Veneziana - Ospedale dell'Angelo	Venezia
Italy	Casa di Cura Villa Margherita	Vicenza
Poland	VITAMED Galaj i Cichomski spólka jawna	Bydgoszcz
Poland	Anna Kapustecka Prywatna Przychodnia Specjalistyczna STOMED	Czestochowa
Poland	Centrum Medyczne Pratia Katowice I	Katowice
Poland	NEURO-CARE Site Management Organization Gabriela Klodowska-Duda	Katowice
Poland	Krakowska Akademia Neurologii Sp. z o. o.	Krakow
Poland	Gabinet Lekarski Prof. Andrzej Bogucki	Lodz
Poland	Centrum Medyczne Damiana Holding	Warszawa	Mazowieckie
Poland	Centrum Medyczne Pratia Warszawa	Warszawa
Slovakia	Neurologicka ambulancia, Euro-Neuro s.r.o.	Bratislava
Slovakia	KONZÍLIUM s.r.o.	Považská Bystrica
Slovakia	NEURON - D.T. s.r.o.	Zilina
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Quirón Dexeus	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Puerta de Hierro Majadahonda	Majadahonda
Spain	HM Puerta del Sur	Mostoles	Madrid
Spain	Hospital Infanta Sofía	San Sebastian de los Reyes
Spain	Hospital General de Cataluña	Sant Cugat del Valles
Ukraine	Ukrainian State Scientific Research Institution of Medical and Social Problems of Disability	Cherkasy
Ukraine	Dnipropetrovsk medical academy MOH of Ukraine	Dnipropetrovs'k
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	Lviv City Clinical Hospital	L'viv
Ukraine	Regional Clinical Hospital n.a. N.V. Sklifosovskyi	Poltava
Ukraine	Municipal Institution "Zaporizhzhya City Clinical Multidisciplinary Hospital #9"	Zaporizhzhya
Ukraine	Municipal Institution 6¿ City Clinical Hospital	Zaporizhzhya
Ukraine	Clinical Hospital #2	Zaporozh'ye
Ukraine	Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council	Zaporozh'ye
United Kingdom	Fairfield General Hospital	Bury
United Kingdom	Newcastle University Clinical Ageing Research	Newcastle upon Tyne
United Kingdom	Queens Medical Centre Nottingham, University Hospital	Nottingham
United Kingdom	University Hospitals of North Midlands NHS Trust	Stoke-on-Trent
United States	Asheville Neurology Specialists	Asheville	North Carolina
United States	University of Colorado Dept. of Neurology	Aurora	Colorado
United States	North Texas Movement Disorders Institute	Bedford	Texas
United States	University Alabama Hospital Neurology	Birmingham	Alabama
United States	Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Charlottesville Medical Research	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	David L. Kreitzman, MD., PC	Commack	New York
United States	Michigan State University	East Lansing	Michigan
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Parkinson's Disease & Movement Disorders Center, Dept of Neu	Fountain Valley	California
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine Department of Neurology	Houston	Texas
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	Booth Garner Parkinson's Care Center	Kirkland	Washington
United States	Dartmouth Hitchcock Neurology	Lebanon	New Hampshire
United States	Loma Linda University Medical Center	Loma Linda	California
United States	University of Southern California	Los Angeles	California
United States	Collier Neurologic Specialists, LLC	Naples	Florida
United States	Vanderbilt University Medical Center Vanderbilt Clinical Neurosciences	Nashville	Tennessee
United States	Fresco Institute for Parkinson's and Movement Disorders	New York	New York
United States	Weill Cornell Medical College of Cornell University	New York	New York
United States	Bioclinica Research	Orlando	Florida
United States	SC3 Research	Pasadena	California
United States	Saint Joseph's Hospital and Medical Center Muhammad Ali Parkinson Research Center	Phoenix	Arizona
United States	SC3 Research	Reseda	California
United States	UC Davis Medical Center	Sacramento	California
United States	Atlantic Health System Hospital Corp.-Overlook Hospital	Summit	New Jersey
United States	Parkinson's Disease and Movement Disorders Center	Tampa	Florida
United States	University of Toledo	Toledo	Ohio
United States	The Movement Disorder Clinic of Oklahoma	Tulsa	Oklahoma
United States	Hartford HealthCare	Vernon	Connecticut
United States	Henry Ford Hospital	West Bloomfield	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Intec Pharma Ltd.

Countries where clinical trial is conducted

United States,  Bulgaria,  Germany,  Israel,  Italy,  Poland,  Slovakia,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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,
Secondary	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