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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)

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ClinicalTrials.gov Identifier: NCT03391882
Recruitment Status : Recruiting
First Posted : January 5, 2018
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Sunovion

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)

Condition or disease Intervention/treatment Phase
Motor OFF Episodes Associated With Parkinson's Disease Drug: APL-130277 Drug: subcutaneous apomorphine Phase 3

Detailed Description:

An Open-Label, Randomized, Crossover Trial utilizing a Single-Blinded Rater to evaluate APL-130277 compared to s.c. Apomorphine in Levodopa Responsive Subjects with Parkinson's Disease Complicated by Motor Fluctuations.

PART A consists of an open label, crossover titration phase where eligible subjects will be randomized to 1 of 2 treatment sequences in a 1:1 ratio to Sublingual APL 130277 followed by subcutaneous apomorphine or subcutaneous apomorphine followed by sublingual APL 130277. Subjects will undergo dose titration with the first study treatment (APL 130277 or sc apomorphine) to tolerance and effect, ie, the tolerable dose that turns the subject from the practically defined "OFF" state to the full "ON" state as determined by both the Investigator and subject. The subject will then be crossed over to the other study treatment (APL 130277 or subcutaneous apomorphine) and similarly titrated to tolerance and effect. These determined doses of APL 130277 and subcutaneous apomorphine will be used during PART B.

PART B consists of an open-label, crossover treatment period where subjects will be randomized to one of the study treatment for 4 weeks, then be crossed over to the other study treatment (APL-130277 or sc apomorphine) for additional 4-weeks of open-label treatment. Subjects return to the clinic for safety and efficacy assessments throughout the treatment period.

This study is designed to test the superiority of sublingually administered APL-130277 against subcutaneously injected apomorphine (APO-go) for the treatment of "OFF" episodes in patients with Parkinson's Disease, as measured by the change from pre-dose to 90 minutes post-dose in MDS UPDRS Part III score in Part B after 4 weeks of dosing in each crossover period.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 106 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Masking Description:

Open label: APL-130277 and Subcutaneous Apomorphine

Single-Blinded Rater for MDS-UPDRS Part III Motor Examination assessment in Part B.

Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Crossover Trial Utilizing a Single-Blinded Rater to Evaluate APL-130277 Compared to Subcutaneous Apomorphine in Levodopa Responsive Subjects With Parkinson's Disease Complicated by Motor Fluctuations
Actual Study Start Date : December 19, 2018
Estimated Primary Completion Date : March 24, 2020
Estimated Study Completion Date : March 24, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: APL-130277
APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
Drug: APL-130277
APL-130277: Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
Other Name: Apomorphine Hydrochloride

Active Comparator: subcutaneous apomorphine
subcutaneous apomorphine , Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
Drug: subcutaneous apomorphine
subcutaneous apomorphine Part A- determine the dose; Part B- 28-day repeat dosing at the dose determined in Part A
Other Name: APO-go®




Primary Outcome Measures :
  1. change from pre-dose to 90 minutes post-dose in MDS UPDRS 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). [ Time Frame: Week 4 ]

Secondary Outcome Measures :
  1. 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). [ Time Frame: Week 4 ]
  2. Subject preference for treatment regimen as measured by the Subject Preference Visual Analog Scale (VAS) after the subject has completed both APL 130277 and sc apomorphine treatment regimens (assessed in-clinic at Visit 6 of PART B). [ Time Frame: Week 4 ]
    with a recorded range of -50 to 50. Negative values indicate preference for SC treatment, and the more negative the value, the stronger is the preference for SC compared to APL treatment. Positive values indicate preference for APL treatment, and the more positive the value, the stronger is the preference for APL compared to SC treatment. A value of 0 indicates no preference of one treatment over the other.

  3. Per the Expanded Home Dosing Diary, percent of "ON" episodes without troublesome dyskinesia based on the 3 consecutive days prior to Visit 2, Visit 3, Visit 5, and Visit 6. [ Time Frame: Week 4 ]
  4. 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). [ Time Frame: Week 4 ]
  5. 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). [ Time Frame: Week 4 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Male or female ≥ 18 years of age.
  3. Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria (excluding the "more than one affected relative" criterion).
  4. Clinically meaningful response to levodopa (L-Dopa), as determined by the Investigator.
  5. Subjects at screening must demonstrate an adequate L-Dopa response on the 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.
  6. 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.
  7. No planned medication change(s) or surgical intervention anticipated during the course of study.
  8. 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.
  9. Subject must have predictable morning "OFF" periods, based on judgment of physician and subject self assessment.
  10. Subject, and where appropriate caregiver, must be trained in completing the home dosing diaries and able to recognize "ON" and "OFF" states.
  11. Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
  12. Mini-Mental State Examination (MMSE) score > 25.
  13. 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.
  14. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study related procedures to complete the study.
  15. Must be approved as a satisfactory candidate by the Enrollment Adjudication Committee (EAC), Medical Monitor, and Sponsor.

Exclusion Criteria:

  1. Atypical or secondary parkinsonism.
  2. Major focal brain disorders including malignancy or stroke.
  3. 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.
  4. Contraindications to domperidone, subcutaneous apomorphine, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of subcutaneous apomorphine (notably sodium metabisulfite).
  5. Female who is pregnant or lactating.
  6. Participation in an interventional clinical study and/or receipt of any investigational (ie, unapproved) medication within 30 days prior to SV1.
  7. 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.
  8. 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.
  9. The recreational use of cannabinoids and hallucinogenic are excluded, as well any use of a sublingual formulation of any drug.
  10. 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.
  11. 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.
  12. 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.
  13. Subject has random (non-fasting) screening glucose of ≥ 200 mg/dL (11.1 mmol/L) or HbA1c > 7.0%.
  14. Subjects with type 1 diabetes, or insulin dependent diabetics are excluded. Subjects with type 2 diabetes are eligible for study inclusion if the following conditions are met:

    • 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
    • If the subject is currently being treated with oral anti-diabetic medication(s), the dose must have been stable for at least 4 weeks prior to SV1. Such medication may be adjusted or discontinued during the study, as clinically indicated.
  15. The subject's screening ECG results of corrected QT interval using Fridericia's formula (QTcF) ≥ 450 msec for male subjects or ≥ 470 msec for female subjects. Eligibility will be based on the core laboratory ECG interpretation report.
  16. Subject has a positive screening laboratory test result for human immunodeficiency virus (HIV).
  17. Subject has a positive screening laboratory test result for hepatitis B surface antigen or hepatitis C antibodies and has liver function test results at screening above the ULN for the reference laboratory.
  18. Subject has any other medical disorder that, in the opinion of the Investigator, could interfere with the subject's participation in the study.
  19. Subject has major psychiatric disorder(s), including but not limited to: bipolar disorder, psychosis (eg, Parkinson's Disease Psychosis), major depressive episode, or any disorder that, in the opinion of the Investigator, would require treatment that could make study participation unsafe or make treatment compliance difficult.
  20. History of clinically significant impulse control disorder(s).
  21. History of symptomatic orthostatic hypotension requiring medication.
  22. History of severe dyskinesia based on a score of 4 on the MDS-UPDRS Part IV.
  23. Dementia that precludes providing informed consent or would interfere with participation in the study.
  24. Current/recent suicidal ideation as evidenced by answering "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at screening (using the "screening /Baseline Version" scale, in the past 12 months) or attempted suicide within the last 5 years.
  25. Presence of canker or mouth sores in the 30 days prior to SV1, or other clinically significant oral pathology in the opinion of the Investigator. The Investigator should follow-up with an appropriate specialist on any finding, if indicated, before enrolling a subject into the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03391882


Contacts
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Contact: CNS Medical Director 1-866-503-6351 clinicaltrialdisclosure@sunovion.com

Locations
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Austria
Medical University Innsbruck, Neurolgy Dept Recruiting
Innsbruck, Austria, A-6020
Contact: Werner Poewe, Prof. MD    004351250481553    lik.parkinson@tirol-kliniken.at   
Wilhelminenspital, Department of Neurology Recruiting
Vienna, Austria, A-1160
Contact: Walter Pirker, Prof.    00431491502001      
France
Hopital la Timone, Neurologie et pathologie due mouvement Recruiting
Marseille, France, 13385
Contact: Jean-Phillippe Azulay, MD    +33491384333    secretariat.pr.azulay@ap-hm.fr   
CHU Caremeau, Service de Neurologie Recruiting
Nimes, France, 30029
Contact: Giovanni Castelnovo, MD    +33466683977    elisabeth.llinares@chu-nimes.fr   
Rouen University Hospital, Neurology Recruiting
Rouen, France, 76031
Contact: David Maltete, Prof.    +330232885781      
Centre d'Investigation Clinique, CIC 43, CHU Purpan, Hopital Pierre-Paul Riquet, place du Dr. Baylac, Hall D, 2 eme etage -TSA Recruiting
Toulouse, France, 31059
Contact: Olivier Rascol, Prof.    +33561779114    cic.1436@inserm.fr   
Germany
Klinken Beelitz GmbH Neurologisches Fachkrankenhaus fur Bewegungsstorungen/Parkinson Recruiting
Beelitz-Heilstatten, Germany, 14547
Contact: Florin Gandor, MD    00493320422782    gandor@kliniken-beelitz.de   
Charite-University Medicine Berlin, Department of Neurology, Campus charite Mitte Recruiting
Berlin, Germany, 10117
Contact: Andrea Kuehn, Prof., MD    0049(0)30450660203      
St. Josef Hospital, Klnikum der Ruhr-Universitat-Bochum, Neurologische Klinik Recruiting
Bochum, Germany, 44791
Contact: Siegfired Muhlack, Prof., MD    00492345092703      
Klinik Haag i.OB Recruiting
Haag In Oberbayern, Germany, 83527
Contact: Johannes Schwarz, Professor    004980723783317    bettina.wieder@kliniken-mueldorf.de   
Contact       anja.deuschl@kliniken-mueldorf.de   
Universitaets-und Rehabillitatinskliniken Ulm Recruiting
Ulm, Germany, D-89081
Contact: Jan Rainer Kassubek, Prof., MD    00497311771206    dorothea.hueske@uni-ulm.de   
Italy
San Raffaele Cassino Recruiting
Cassino, Italy, 03043
Contact: Maria Francesca De Pandis, MD    +390776394740    maria.depandis@sanraffaele.it   
University Hospital Policlinico-Vittorio Emanuele, Department "G.F. Ingrassia", Section of Neurosciences Recruiting
Catania, Italy
Contact: Mario Zappia, Professor    00390953782783      
IRCCS San Cmillo di Venezia Recruiting
Lido di Venezia, Italy, 30126
Contact: Elisabetta Gasparoli, MD    +390412207524      
IRCCS San Raffaele Pisana-Clinical Trial Center Recruiting
Rome, Italy, 00163
Contact: Fabrizio Stocchi, Prof.    00390652252311    fabrizio.stocchi@sanraffaele.it   
AOU San Giovanni di Dio e Ruggid'Aragona-CEMAND Recruiting
Salerno, Italy, 84131
Contact: Paolo Barone, MD    0039089969119    pbarone@@unisa.it   
Spain
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Maria Jose Marti, MD    +34932775783    trastornsmovimient@clinic.cat   
Hospital de la Santa Creu i Sant Pau c/Mas de Casanovas 90 Recruiting
Barcelona, Spain, 08041
Contact: Jamie Kulisevsky Bojarski, MD    +34935537613    ctmovement@santpau.cat   
Hospital Universitario de la Princesa Recruiting
Madrid, Spain, 28006
Contact: Lydia Lopez Manzanares, MD    +34915202416      
CINAC, Hospital Universitario HB Pueta del Sur Recruiting
Mostoles, Spain, 28938
Contact: Alvaro Sanchez Ferro, MD    +3491273100    aferro.hmcinac@hmhospitales.com   
Hospital General de Catalunya Recruiting
Sant Cugat del Valles, Spain, 08195
Contact: Ernest Balaguer Martinez, MD    +34931751575    info@udic.es   
United Kingdom
King's College Hospital NHS Foundation Trust Recruiting
London, United Kingdom, SE5 9RS
Contact: K Ray Chaudhuri, Prof.    0044 203 299 7154    ray.chaudhuri@kcl.ac.uk   
10W, Imperial Memory/PD Research Unit, Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom, W6 8RF
Contact: Sophie Molloy, MD    0044 20 8453 3714      
NHS Forth Valley, Pennine Actue NHS Trust, Fairfield General Hospital Recruiting
Manchester, United Kingdom, Bl9 7TD
Contact: Dr. Raw, MD    00441617783868    sanniah.hussain@pat.nhs.uk   
University Hospitals Plymouth NHS Trust-Derriford Hospital-The Lind Research Center, Level 5, Terence Lewis Building Recruiting
Plymouth, United Kingdom, PL6 8DH
Contact: Camille Carroll, MD    00441752439636    plh-tr.integrityresearchteam@nhs.net   
Sponsors and Collaborators
Sunovion
Investigators
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Study Director: CNS Medical Director Sunovion

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Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT03391882     History of Changes
Other Study ID Numbers: CTH-302
2016-003456-70 ( EudraCT Number )
First Posted: January 5, 2018    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Sunovion:
Parkinson's Disease
"Off" Episodes
motor fluctuations associated with Parkinson's Disease

Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Apomorphine
Emetics
Physiological Effects of Drugs
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action