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

• ClinicalTrials.gov Identifier: NCT02242487
• Recruitment Status: Completed
• First Posted: September 17, 2014
• Results First Posted: July 30, 2019
• Last Update Posted: August 14, 2019
• Sponsor: Acorda Therapeutics
• Information provided by (Responsible Party): Acorda Therapeutics

Tracking Information

• First Submitted Date: September 15, 2014
• First Posted Date: September 17, 2014
• Results First Submitted Date: June 12, 2019
• Results First Posted Date: July 30, 2019
• Last Update Posted Date: August 14, 2019
• Study Start Date: March 2015
• Actual Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2019)

• Pulmonary Safety of CVT-301 Change From Baseline for FEV1. [ Time Frame: Change from baseline at 52 weeks ]
  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.
• Pulmonary Safety for CVT-301 Change From Baseline for FVC. [ Time Frame: Change from baseline at 52 weeks ]
  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.
• Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). [ Time Frame: Change from baseline at 52 weeks ]
  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.

Original Primary Outcome Measures (submitted: September 15, 2014)

Pulmonary safety of CVT-301. [ Time Frame: change from baseline through 12 months duration of outpatient use ]

Spirometry assessment of FEV1 and FEV1/FVC ratio

Current Secondary Outcome Measures (submitted: July 10, 2019)

• Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes. [ Time Frame: At Treatment Visit - TV6 (Week 52) ]
  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).
• Change From Baseline in OFF Time. [ Time Frame: Change from baseline through 12 months duration of outpatient use ]
  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.

Original Secondary Outcome Measures (submitted: September 15, 2014)

• Safety and tolerability of CVT-301. [ Time Frame: change from baseline through 12 months duration of outpatient use ]
  Adverse experiences, ECGs, vital signs, clinical laboratory evaluation, pulmonary function using DLco, scales to evaluate suicidality, day time sleepiness, and impulse control disorders
• Change in average Unified Parkinson's Disease Rating Scale Part III motor score [ Time Frame: pre-dose to 60 minutes following treatment ]
• Total daily OFF time and daily ON time ± dyskinesia (troublesome/nontroublesome) [ Time Frame: change from baseline through 12 months duration of outpatient use ]
  Patient recorded PD diary
• Effect of CVT-301 on activities of daily living and quality of life [ Time Frame: change from baseline through 12 months duration of outpatient use ]
  Schwab & England Activities of Daily Living, UPDRS Part 2, PDQ-39

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Twelve Month Safety and Efficacy Study of CVT-301 In Parkinson's Disease Patients With OFF Episodes
• Official Title: 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Idiopathic Parkinson's Disease

Intervention

Drug: CVT-301

Other Name: Inhaled levodopa

Study Arms

• Experimental: CVT-301 Low Dose
  Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration
  Intervention: Drug: CVT-301
• Experimental: CVT-301 High Dose
  Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration
  Intervention: Drug: CVT-301

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2017): 325
• Original Estimated Enrollment (submitted: September 15, 2014): 350
• Actual Study Completion Date: May 2018
• Actual Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 86 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Poland, Spain, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02242487
• Other Study ID Numbers: CVT-301-004E
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Acorda Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Acorda Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Charles Oh, MD; Acorda Therapeutics

• PRS Account: Acorda Therapeutics
• Verification Date: July 2019