A Study of an Investigational Drug to See How it Affects the People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes) Compared to an Approved Drug Used to Treat People With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)

NCT03391882 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CTH-3022016-003456-70
• Study Type: interventional
• Target: 113
• Locations: 6 countries
• Sites: 31

Brief Summary

A study of an investigational drug to see how it affects the people with Parkinson's Disease complicated by motor fluctuations ("OFF" Episodes) compared to an approved drug used to treat people with Parkinson's Disease complicated by motor fluctuations ("OFF" Episodes)

Conditions

Motor OFF Episodes Associated With Parkinson's Disease

Keywords

Parkinson's Disease; "Off" Episodes; motor fluctuations associated with Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Change From Pre-dose to 90 Mins. Post-dose in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Score After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).

  The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. The summary score used in this study for the primary objective and primary efficacy endpoint is Part III motor examination score. Each Part III item has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse motor function. MDS-UPDRS III is a total of 18 questions with 33 individual items, each item ranges from 0-4. The MDS-UPDRS III motor score is the summation of all these 33 individual item scores, and hence ranges from 0-132. Score drops over time imply improvement in motor function (higher values represent a worse outcome).

  Pre-dose to 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)

Secondary Outcomes (4)

• Durability of Effect, Defined as an Investigator Confirmed Full "ON" Within 30 Minutes Post Dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed by the Blinded-rater In-clinic at Visit 3 and Visit 6 of PART B).

  Within 30 minutes post-dose and at 90 minutes post-dose at Week 4 of each treatment period (Visit 3 and 6)

• Subject Preference for APL Treatment as Measured by the Subject Treatment Preference Questionnaire (TPQ), Planned After the Subject Had Completed Both APL-130277 and sc Apomorphine Treatment Regimens (Assessed In-clinic at Visit 6 of PART B)

  After 8 weeks of treatment (Visit 6)

• Subject Confirmed Durability of Effect, Defined as Subject Confirmed Full "ON" Within 30 Minutes Post-dose and at 90 Minutes Post-dose, After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).

  Week 4

• Patient Global Impression of Change (PGI-C): Subject Improvement of "OFF" Episodes, Defined as Very Much Better, Much Better or a Little Better After 4 Weeks of Dosing in Each Crossover Period (Assessed In-clinic at Visit 3 and Visit 6 of PART B).

  At Week 4 of each treatment period (Visit 3 and 6, or Early Termination)

Study Arms (2)

APL-130277

EXPERIMENTAL

APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

Drug: APL-130277

subcutaneous apomorphine

ACTIVE COMPARATOR

subcutaneous apomorphine , Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

Drug: subcutaneous apomorphine

Interventions

APL-130277 DRUG

APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

Also known as: Apomorphine Hydrochloride

APL-130277

subcutaneous apomorphine DRUG

subcutaneous apomorphine Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A

Also known as: APO-go®

subcutaneous apomorphine

Eligibility Criteria

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

You may qualify if:

• The subject (and caregiver, if applicable) must be fully informed of and understand the objectives, procedures, and possible benefits and risks of the study, and give written informed consent prior to performing any study related activities.
• Male or female ≥ 18 years of age.
• Clinical diagnosis of Idiopathic Parkinson's disease (PD), consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
• Clinically meaningful response to levodopa (L-Dopa), as determined by the Investigator.
• Subjects at screening must demonstrate an adequate L-Dopa response on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS) Part III in the "ON" state compared to the MDS UPDRS Part III in the "OFF" state and on the Hoehn and Yahr, as determined during the review by Enrollment Adjudication Committee (EAC), Sponsor, and Medical Monitor.
• 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 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.
• No planned medication change(s) or surgical intervention anticipated during the course of study.
• Subjects must experience at least one well defined "OFF" episode per day and have a total daily "OFF" time duration of \> 2 hours during the waking day, based on judgment of physician and subject self assessment.
• Subject must have predictable morning "OFF" periods, based on judgment of physician and subject self assessment.
• Subject, and where appropriate caregiver, must be trained in completing the home dosing diaries and able to recognize "ON" and "OFF" states.
• Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
• Mini-Mental State Examination (MMSE) score \> 25.
• Female subject of childbearing potential and male subject with female partner of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and for at least 7 days after the last dose of study drug has been taken. Note: Continued use of adequate and reliable contraception is recommended through 30 days after study completion.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study related procedures to complete the study.
• Must be approved as a satisfactory candidate by the Enrollment Adjudication Committee (EAC), Medical Monitor, and Sponsor.

You may not qualify if:

• Atypical or secondary parkinsonism.
• Major focal brain disorders including malignancy or stroke.
• Prior treatment with any of the following: a neurosurgical procedure for PD; continuous subcutaneous (subcutaneous) apomorphine infusion; subcutaneous (subcutaneous) apomorphine injection; Duodopa/Duopa; or APL-130277.
• Contraindications to domperidone, subcutaneous apomorphine, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of subcutaneous apomorphine (notably sodium metabisulfite).
• Female who is pregnant or lactating.
• Participation in an interventional clinical study and/or receipt of any investigational (ie, unapproved) medication within 30 days prior to SV1.
• 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 prior to SV1.
• The subject has a current diagnosis or history of substance abuse (excluding nicotine and caffeine) or alcohol abuse (in the opinion of the investigator) \< 6 months prior to SV1.
• The recreational use of cannabinoids and hallucinogenic are excluded, as well any use of a sublingual formulation of any drug.
• 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.
• Subject has a clinically significant abnormality on screening evaluation including physical examination, vital signs, electrocardiogram (ECG), or laboratory tests that the Investigator considers to be inappropriate to allow participation in the study.
• 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.
• Subject has random (non-fasting) screening glucose of ≥ 200 mg/dL (11.1 mmol/L) or HbA1c \> 7.0%.
• Subject's screening glucose is \< 200 mg/dL (11.1 mmol/L). Note: Subjects with random (non fasting) blood glucose at screening ≥ 200 mg/dL (11.1 mmol/L) must be retested in a fasted state; and
• Subject's hemoglobin A1c (HbA1c) ≤ 7.0%; and

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (31)

Medical University Innsbruck, Neurolgy Dept

Innsbruck, A-6020, Austria

Location

Wilhelminenspital, Department of Neurology

Vienna, A-1160, Austria

Location

CHU Caremeau, Service de Neurologie

Nîmes, 30029, France

Location

Centre d'Investigation Clinique, CIC 43, CHU Purpan, Hopital Pierre-Paul Riquet, place du Dr. Baylac, Hall D, 2 eme etage -TSA

Toulouse, 31059, France

Location

Klinken Beelitz GmbH Neurologisches Fachkrankenhaus fur Bewegungsstorungen/Parkinson

Beelitz-Heilstätten, 14547, Germany

Location

Charite-University Medicine Berlin, Department of Neurology, Campus charite Mitte

Berlin, 10117, Germany

Location

St. Joseph Krankenhaus Berlin - Weissensee, Abteilung fur Neurologie

Berlin, 13088, Germany

Location

St. Josef Hospital, Klnikum der Ruhr-Universitat-Bochum, Neurologische Klinik

Bochum, 44791, Germany

Location

Universitatsklinikum Carol Gustav Carus an der TU dDresden, Klinik umd Poliklinik fur Neurologie

Dresden, 01307, Germany

Location

Klinik Haag i.OB

Haag in Oberbayern, 83527, Germany

Location

Curiositas ad sanum GmbH

Munich, 80331, Germany

Location

Klinikum rechts der Isar der Technischen Universitat Munchen

München, 81675, Germany

Location

Universitaets-und Rehabillitatinskliniken Ulm

Ulm, D-89081, Germany

Location

San Raffaele Cassino

Cassino, 03043, Italy

Location

University Hospital Policlinico-Vittorio Emanuele, Department "G.F. Ingrassia", Section of Neurosciences

Catania, Italy

Location

A.O.U. Universita degli Studi della Campania "Luigi Vanvitelli" Dipartamento di Scienze Mediche e Chirurgiche Avanzate

Napoli, 80138, Italy

Location

IRCCS San Raffaele Pisana-Clinical Trial Center

Rome, 00163, Italy

Location

Istituto Clinico Humanitas, Dipartmento di Neurologia 1

Rozzano, 20089, Italy

Location

AOU San Giovanni di Dio e Ruggid'Aragona-CEMAND

Salerno, 84131, Italy

Location

Hospital Universitario de Cruces, Neurology

Barakaldo, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau c/Mas de Casanovas 90

Barcelona, 08041, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

CINAC, Hospital Universitario HB Pueta del Sur

Móstoles, 28938, Spain

Location

Hospital General de Catalunya

Sant Cugat del Vallès, 08195, Spain

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

10W, Imperial Memory/PD Research Unit, Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

NHS Forth Valley, Pennine Actue NHS Trust, Fairfield General Hospital

Manchester, Bl9 7TD, United Kingdom

Location

Academic Neuroscience Department, C Floor, South Block, Nottingham University Hospitals NHS Trust Queens Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

University Hospitals Plymouth NHS Trust-Derriford Hospital-The Lind Research Center, Level 5, Terence Lewis Building

Plymouth, PL6 8DH, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Apomorphine

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)

Aporphines; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Results Point of Contact

• Title: CNS Medical Director
• Organization: Sunovion Pharmaceuticals Inc.

clinicaltrialdisclosure@sunovion.com

1-866-503-6351

Study Officials

• CNS Medical Director

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open label: APL-130277 and Subcutaneous Apomorphine Single-Blinded Rater for MDS-UPDRS Part III Motor Examination assessment in Part B.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 5, 2018
• Study Start: December 19, 2018
• Primary Completion: August 11, 2021
• Study Completion: August 11, 2021
• Last Updated: December 16, 2022
• Results First Posted: December 16, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: IPD will be made available upon request within 12 months of posting the study results on ct.gov.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (5); FR (2); IT (6); ES (7); DE (9); AU (2)