Clinical trial NCT02469090: Efficacy, Safety and Tolerability Study of APL-130277 for the Acute Treatment of OFF Episodes in Patients With Parkinson's Disease
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Examine the Efficacy, Safety and Tolerability of APL-130277 in Levodopa Responsive Patients With Parkinson's Disease Complicated by Motor Fluctuations ("OFF" Episodes)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease, Off Episodes
Keywords: Parkinson Disease, off episodes
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-11
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A 12-week, prospective, multi-center, randomized, double-blind, placebo controlled, Phase 3 study in L-Dopa responsive PD patients with motor fluctuations ("OFF" episodes), designed to determine the efficacy, safety and tolerability of APL-130277.


Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 18 years of age.
* Clinical diagnosis of Idiopathic PD, consistent with UK Brain Bank Criteria.
* Clinically meaningful response to L-Dopa with well-defined early morning "OFF" episodes, as determined by the Investigator.
* Receiving stable doses of L-Dopa/carbidopa (immediate or CR) administered at least 4 times per day OR Rytary™ administered 3 times per day, for at least 4 weeks before the initial Screening Visit
* No planned medication change(s) or surgical intervention anticipated during the course of study.
* Patients must experience at least one well defined "OFF" episode per day with a total daily "OFF" time duration of ≥ 2 hours during the waking day, based on patient self-assessment.
* Stage III or less on the modified Hoehn and Yahr scale in the "ON" state.
* MMSE score \> 25.

Exclusion Criteria:

A patient will not be eligible for study entry if any of the following exclusion criteria are met:

* Atypical or secondary parkinsonism.
* Previous treatment with any of the following: a neurosurgical procedure for PD; continuous s.c. apomorphine infusion; or Duodopa/Duopa.
* Treatment with any form of s.c. apomorphine within 7 days prior to the initial Screening Visit (SV1). Patients that stopped s.c. apomorphine for any reason other than systemic safety concerns or lack of efficacy may be considered.
* Contraindications to APOKYN®, or hypersensitivity to apomorphine hydrochloride or any of the ingredients of APOKYN® (notably sodium metabisulfite); Tigan® (trimethobenzamide hydrochloride; patients from US sites only); or domperidone (patients from non-US sites only).
* Participation in a clinical trial within 30 days prior to the initial Screening Visit (SV1).
* Currently taking selective 5HT3 antagonists (i.e., ondansetron, granisetron, dolasetron, palonosetron, alosetron), dopamine antagonists (excluding quetiapine or clozapine) or dopamine depleting agents.
* Drug or alcohol dependency in the past 12 months.
* History of malignant melanoma.
* Clinically significant medical, surgical, or laboratory abnormality in the opinion of the Investigator.
* Major psychiatric disorder including, but not limited to, dementia, bipolar disorder, psychosis, or any disorder that, in the opinion of the Investigator, requires ongoing treatment that would make study participation unsafe or make treatment compliance difficult.
* History of clinically significant hallucinations during the past 6 months.
* History of clinically significant impulse control disorder(s).
* Dementia that precludes providing informed consent or would interfere with participation in the study.

Primary outcomes:
measure: Mean Change From Pre-Dose to 30 Minutes Post-Dose in The Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III Motor Examination (MDS-UPDRS Part III) Score at Maintenance Visit 4 (MV4) - Week 12
timeFrame: At t=0 (just prior to dosing) and t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).
Secondary outcomes:
measure: Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes at MV4 - Week 12: Predicted Response Rate
timeFrame: At t=30 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Percentage of Patients With a Patient-related Full 'ON' Response Within 30 Minutes That Had a Duration of Effect of at Least 30 Minutes at MV4 - Week 12: Predicted Response Rate
timeFrame: At MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Patient Global Impression of Improvement (PGI-I): Percentage of Patients Who Improved at MV4 - Week 12
timeFrame: At MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Clinician Global Impression of Improvement (CGI-I): Percentage of Patients Who Improved at MV4 - Week 12
timeFrame: At MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Mean Change From Screening Visit to MV4 (Week 12) in MDS-UPDRS Part II: Motor Aspects of Experience of Daily Living
timeFrame: At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Mean Percentage of Instances Where a Full 'ON' Response Was Achieved at 30 Minutes Post-dose on the Home Dosing Diary Entries During the 2 Days Prior to MV4 - Week 12
timeFrame: 2 days prior to MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Mean Change From Screening Visit to MV4 in the Parkinson's Disease Quality of Life Questionnaire (PDQ-39) Summary Index Score
timeFrame: At Screening Visit and at MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Mean Change From Pre-Dose to 15 Minutes Post-Dose in the MDS-UPDRS Part III Score at MV4 - Week 12
timeFrame: At t=0 (just prior to dosing) and t=15 minutes at MV4 (Week 12 of the Maintenance Treatment Phase).
measure: Time From Dosing to When Study Medication Provided an Effect at MV4 - Week 12
timeFrame: At MV4 (Week 12 of the Maintenance Treatment Phase).
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Muhammed Ali Parkinson and Movement Disorder CenterBarrow Neurological
state: Arizona
city: Scottsdale
country: United States
facility: Movement Disorders Center of Arizona
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Fountain Valley
country: United States
facility: The Parkinson's and Movement Disorder Institute
state: California
city: Irvine
country: United States
facility: UC Irvine Health Gottschalk Medical Plaza
state: California
city: Los Angeles
country: United States
facility: Keck Medical Center at USC
state: California
city: Oceanside
country: United States
facility: The Research Center of Southern California
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Boca Raton
country: United States
facility: Parkinsons Disease and Movement Disorders Center
state: Florida
city: Miami
country: United States
facility: University of Miami, Miller School of Medicine
state: Florida
city: Port Charlotte
country: United States
facility: Parkinson's Disease Treatment Center of Southwest Florida
state: Florida
city: Tampa
country: United States
facility: USF Parkinson's Disease and Movement Disorder Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Department of Neurology
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Winfield
country: United States
facility: Central DuPage Hospital - Neurodegenerative Clinic - Movement Disorders Center
state: Illinois
city: Kansas City
country: United States
facility: Kansas University Medical Center - Department of Neurology
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: Traverse City
country: United States
facility: Northern Michigan Neurology
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford Hospital
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center - Neurological Institute, Movement Disorders
state: New York
city: Raleigh
country: United States
facility: Raleigh Neurology Associates, P.A.
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Jefferson University Hospital Philadelphia
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia, Adult Neurology
state: Virginia
city: Kirkland
country: United States
facility: Evergreen Health
state: Washington
city: Toronto
country: Canada
facility: UHN Toronto Western Hospital
state: Ontario
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: CNS Medical Director
role: STUDY_DIRECTOR
References:
citation: Olanow CW, Factor SA, Espay AJ, Hauser RA, Shill HA, Isaacson S, Pahwa R, Leinonen M, Bhargava P, Sciarappa K, Navia B, Blum D; CTH-300 Study investigators. Apomorphine sublingual film for off episodes in Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 study. Lancet Neurol. 2020 Feb;19(2):135-144. doi: 10.1016/S1474-4422(19)30396-5. Epub 2019 Dec 7.