Twelve Month Safety and Efficacy Study of CVT-301 In Parkinson's Disease Patients With OFF Episodes

A 12 Month, Dose-Level Blinded Study Investigating the Safety and Efficacy of CVT 301 (Levodopa Inhalation Powder) in Parkinson's Disease Patients With Motor Response Fluctuations (OFF Phenomena)

This study is a 12-month, dose-level blinded, multicenter study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF episodes per day in PD patients experiencing motor fluctuations (OFF episodes). All patients will receive active treatment, but patients will be blinded to dose level. This will serve as an extension to the CVT-301-004 (NCT02240030) study for those patients who participated in that study and remain eligible for this study. In addition, patients who previously completed the CVT-301-003 (NCT01777555), CVT-301-009 (NCT02807675) and CVT-301-005 (NCT02352363) (observational arm completers), as well as CVT-301 naïve patients may be enrolled if they meet the CVT-301-004E eligibility criteria.

Study Overview

• Status: Completed
• Conditions: Idiopathic Parkinson's Disease
• Intervention / Treatment: Drug: CVT-301

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • Acorda Site #5103
    • Ottawa, Ontario, Canada, K1Y4E9
      • Acorda Site #5104
    • Toronto, Ontario, Canada, M5T2S8
      • Acorda Site #5105
• Czechia
  • Prague, Czechia, 10000
    • Acorda Site #5201
  • Prague, Czechia, 14000
    • Acorda Site #5203
• Poland
  • Katowice, Poland, 40588
    • Acorda Site #5304
  • Krakow, Poland, 30510
    • Acorda Site #5303
  • Kraków, Poland, 30349
    • Acorda Site #5306
  • Kraków, Poland, 31505
    • Acorda Site #5307
  • Lodz, Poland, 90130
    • Acorda Site #5302
  • Warsaw, Poland, 00453
    • Acorda Site #5308
  • Warsaw, Poland, 01868
    • Acorda Site #5301
  • Zappa
    • Gdańsk, Zappa, Poland, 80462
      • Acorda Site #5305
• Spain
  • Barcelona, Spain, 08026
    • Acorda Site #5404
  • Barcelona, Spain, 08035
    • Acorda Site #5406
  • Madrid, Spain, 28006
    • Acorda Site #5405
  • San Sebastián, Spain, 20009
    • Acorda Site #5403
  • Sant Cugat Del Vallès, Spain, 08190
    • Acorda Site #5401
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Acorda Site #5407
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Acorda Site #5020
  • California
    • Fresno, California, United States, 93710
      • Acorda Site #5042
    • Fullerton, California, United States, 92835
      • Acorda Site #5064
    • Loma Linda, California, United States, 92354
      • Acorda Site #5035
    • Long Beach, California, United States, 90806
      • Acorda Site #5027
    • Los Angeles, California, United States, 90033
      • Acorda Site #5037
    • Pasadena, California, United States, 91105
      • Acorda Site #5070
    • Reseda, California, United States, 91335
      • Acorda Site #5047
    • Santa Ana, California, United States, 92705
      • Acorda Site #5068
    • Torrance, California, United States, 90505
      • Acorda Site #5069
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Acorda Site #5052
  • Florida
    • Atlantis, Florida, United States, 33462
      • Acorda Site #5046
    • Aventura, Florida, United States, 33180
      • Acorda Site #5053
    • Boca Raton, Florida, United States, 33486
      • Acorda Site #5013
    • Jacksonville, Florida, United States, 32209
      • Acorda Site #5016
    • Maitland, Florida, United States, 32751
      • Acorda Site #5071
    • Orlando, Florida, United States, 32806
      • Acorda Site #5044
    • Palm Beach Gardens, Florida, United States, 33410
      • Acorda Site #5060
    • Port Charlotte, Florida, United States, 33952
      • Acorda Site #5001
    • Saint Petersburg, Florida, United States, 33713
      • Acorda Site #5065
    • Tampa, Florida, United States, 33613
      • Acorda Site #5012
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Acorda Site #5040
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Acorda Site #5025
    • Chicago, Illinois, United States, 60612
      • Acorda Site #5030
    • Elk Grove Village, Illinois, United States, 60007
      • Acorda Site #5011
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Acorda Site #5003
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70810
      • Acorda Site #5067
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Acorda Site #5057
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Acorda Site #5056
    • Boston, Massachusetts, United States, 02118
      • Acorda Site #5018
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Acorda Site #5002
    • West Bloomfield, Michigan, United States, 48322
      • Acorda Site #5014
  • Minnesota
    • Golden Valley, Minnesota, United States, 55427
      • Acorda Site #5041
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Acorda Site #5006
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Acorda Site #5023
  • New York
    • Albany, New York, United States, 12208
      • Acorda Site #5028
    • Brooklyn, New York, United States, 11203
      • Acorda Site #5039
    • New York, New York, United States, 10016
      • Acorda Site #5031
    • New York, New York, United States, 10029
      • Acorda Site #5032
    • New York, New York, United States, 10032
      • Acorda Site #5004
    • Syracuse, New York, United States, 13210
      • Acorda Site #5038
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Acorda Site #5048
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Acorda Site #5005
    • Norwood, Ohio, United States, 45212
      • Acorda Site #5050
  • Oregon
    • Portland, Oregon, United States, 97239
      • Acorda Site #5062
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Acorda Site #5036
    • Philadelphia, Pennsylvania, United States, 19107
      • Acorda Site #5010
    • Willow Grove, Pennsylvania, United States, 19090
      • Acorda Site #5058
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Acorda Site #5022
  • Tennessee
    • Nashville, Tennessee, United States, 372322551
      • Acorda Site #5029
  • Texas
    • Houston, Texas, United States, 77030
      • Acorda Site #5019
    • Houston, Texas, United States, 77030
      • Acorda Site #5045
  • Virginia
    • Henrico, Virginia, United States, 23226
      • Acorda Site #5049
    • Virginia Beach, Virginia, United States, 23456
      • Acorda Site #5059
  • Washington
    • Kirkland, Washington, United States, 98034
      • Acorda Site #5051

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Idiopathic Parkinson's Disease (PD) diagnosed between the ages of 30 and 80 years;
• Hoehn and Yahr Stage 1-3 in an "on" state;
• Require levodopa-containing medication regimen at least 3 times during the waking day;
• Experience motor fluctuations with a minimum of 2 hours of average daily "off" time per waking day (excluding early morning "off" time) and demonstrate levodopa responsiveness;
• Are on stable PD medication regimen;
• Total daily levodopa (LD) dose <1600 mg/day;
• Able to perform a spirometry maneuver in the ON and OFF states
• Normal cognition confirmed by Mini Mental State Examination (MMSE) score ≥25 ;

Exclusion Criteria:

• Pregnant or lactating females;
• Previous surgery for PD or plan to have stereotactic surgery during the study period. Patients who have had deep brain stimulation [DBS] will also be excluded unless the procedure was performed more than 6 months prior to study enrollment.
• History of psychotic symptoms requiring treatment, or suicide ideation or attempt within last year;
• Known contraindication to the use of levodopa;
• Any significant condition, severe concurrent disease, abnormality or finding that would make patients unsuitable or may compromise patient safety;
• Any any contraindication to performing routine spirometry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CVT-301 Low Dose; Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration	Drug: CVT-301; Other Names: Inhaled levodopa
Experimental: CVT-301 High Dose; Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration	Drug: CVT-301; Other Names: Inhaled levodopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Safety of CVT-301 Change From Baseline for FEV1.	To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1 (forced expiratory volume in 1 second) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.	Change from baseline at 52 weeks
Pulmonary Safety for CVT-301 Change From Baseline for FVC.	To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FVC, (forced vital capacity) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.	Change from baseline at 52 weeks
Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC).	To characterize the effects of CVT-301 on pulmonary safety, as assessed by spirometry FEV1/FVC (FEV1-forced expiratory volume in 1 second and (FVC) forced vital capacity ratio) by treatment group and Treatment Visit (TV). This study was a 12-month, dose-level blinded, multi-center study of 2 inhaled dose levels of CVT-301 for the treatment of up to 5 OFF periods per day in PD (Parkinson's Disease) patients experiencing motor fluctuations (OFF periods). Baseline is defined as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004 study and as the last non-missing assessment before the first dose of CVT-301 in CVT-301-004E study for the rest of the patients.	Change from baseline at 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes.	Count of patients achieving resolution of an OFF to an ON state within 60 minutes after study drug is administered in the clinic, and maintaining the ON state at 60 minutes after study drug administration (per the examiner's subjective assessment).	At Treatment Visit - TV6 (Week 52)
Change From Baseline in OFF Time.	Patient reported total daily OFF time and was assessed by the patient and recorded in the patient Diary. An "OFF state" is defined as the time when medication is not providing benefit with respect to mobility, slowness, and stiffness. OFF episodes may be heralded by non-motor symptoms (e.g., pain, anxiety) prior to the appearance of motor symptoms. Patients will record their ON and OFF states in their diaries at home.	Change from baseline through 12 months duration of outpatient use

Collaborators and Investigators

• Sponsor: Acorda Therapeutics
• Investigators: Study Director: Charles Oh, MD, Acorda Therapeutics

Publications and helpful links

Helpful Links

• Click here for more information about this study:CVT-301-004E

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: September 15, 2014
• First Submitted That Met QC Criteria: September 15, 2014
• First Posted (Estimate): September 17, 2014

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Parkinson's Disease; levodopa; Motor fluctuations; inhaled drugs; OFF episodes
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: CVT-301-004E