Idiopathic Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, Motor fluctuations, levodopa, inhaled drugs, OFF episodes
Brief summary
This study is a 12-month, open-label, randomized, multicenter study which will evaluate the safety and efficacy of CVT-301 for the treatment of up to 5 OFF episodes per day in Parkinson's Disease (PD) patients experiencing motor fluctuations (OFF episodes) and will include a concurrent observational cohort of PD patients managed using the usual standards of care.
Detailed description
A randomized, double-blind, placebo-controlled, Phase 2b study in patients with PD (CVT-301-003) demonstrated clinically important, and statistically significant CVT-301-associated improvements in motor function at doses of 35 and 50 mg LD FPD, compared with placebo, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) motor assessment (Part 3); furthermore, CVT-301 was generally safe and well tolerated. A Phase 3, randomized, placebo-controlled study designed to assess the efficacy and safety of 35 mg and 50 mg FPD as an adjunct to a CD/LD regimen in the treatment of OFF symptoms over 12 weeks (CVT-301-004) was conducted in parallel with this study.
Interventions
DRUGCVT-301
OTHERObservational cohort
Sponsors
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Has signed and dated an Internal Review Board/Independent Ethics Committee (IRB/IEC)-approved informed consent form before any protocol-specific screening procedures are performed. * Women of child-bearing potential must use protocol-defined contraceptive measures and must have a negative serum human chorionic gonadotropin (hCG) test at screening. These patients must be willing to remain on their current form of contraception for the duration of the study. * Patients who have idiopathic PD (i.e., not induced by drugs or other diseases) as defined by fulfilling Steps 1 and 2 of the United Kingdom (UK) Brain Bank criteria, diagnosed after the age of 30 years. * Patients who are classified as Stage 1 to 3 (in the ON state) on the modified Hoehn and Yahr scale for staging of PD severity. * Patients who have experienced motor fluctuations for a minimum of 2 hours of average daily OFF time per waking day (excluding early morning OFF time) by self-report and confirmed by the PD Diary (on 3 consecutive days) during the screening period.
Exclusion criteria
* Patients who have dyskinesia of a severity that would significantly interfere with their ability to participate or perform study procedures. * Pregnant or lactating females or females wishing to become pregnant. * Patients who have any known contraindication to the use of levodopa (LD), including a history of malignant melanoma or a history of narrow-angle glaucoma. * Patients who have had previous surgery for PD (including but not limited to deep brain stimulation \[DBS\] or cell transplantation). * Patients with a history of psychotic symptoms requiring treatment, or suicide ideation or attempt within the prior 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second [FEV1] | Month 12 reported | To characterize the pulmonary safety, as assessed by spirometry (forced expiratory volume in 1 second \[FEV1\], over a 12 month period. |
| Pulmonary Safety Assessed by Forced Vital Capacity [FVC]. | Month 12 reported | To characterize the pulmonary safety, as assessed by spirometry (forced vital capacity). |
| Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second / Forced Vital Capacity Ratio. | Month 12 reported | To characterize the pulmonary safety, as assessed by spirometry (forced expiratory volume in 1 second / forced vital capacity ratio). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diffusion Capacity of the Lungs for Carbon Monoxide (DLco). | Month 12 reported | To describe the effects of CVT-301 on diffusion capacity of the lungs for carbon monoxide (DLco) over a 12-month period. |
Countries
Austria, Belgium, Czechia, France, Germany, Hungary, Israel, Netherlands, Poland, Romania, Serbia, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 408 of the 513 screened were randomly assigned to CVT-301 (278) or observational cohort (130). Of these 408 patients, 398 received at least 1 dose of inhaled CVT-301 CVT-treatment group) or came in for OV1 (observational cohort) and were included in the Safety Population.
Participants by arm
| Arm | Count |
|---|---|
| CVT-301 Capsules of Levodopa Inhalational Powder (LIP) used up to 5 times per day for OFF episodes, for up to 54 weeks duration.
CVT-301 | 271 |
| Observational Cohort Standard of care. Patients in both the CVT-301 treatment group and the observational cohort will be managed with their standard PD treatment throughout the study.
Observational cohort | 127 |
| Total | 398 |
Baseline characteristics
| Characteristic | CVT-301 | Observational Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 134 Participants | 68 Participants | 202 Participants |
| Age, Categorical Between 18 and 65 years | 137 Participants | 59 Participants | 196 Participants |
| Age, Continuous | 63.6 years STANDARD_DEVIATION 8.54 | 64.2 years STANDARD_DEVIATION 7.88 | 63.8 years STANDARD_DEVIATION 8.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 267 Participants | 124 Participants | 391 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Austria | 11 Participants | 1 Participants | 12 Participants |
| Region of Enrollment Belgium | 4 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Czechia | 22 Participants | 16 Participants | 38 Participants |
| Region of Enrollment France | 13 Participants | 7 Participants | 20 Participants |
| Region of Enrollment Germany | 21 Participants | 7 Participants | 28 Participants |
| Region of Enrollment Hungary | 5 Participants | 0 Participants | 5 Participants |
| Region of Enrollment Israel | 15 Participants | 6 Participants | 21 Participants |
| Region of Enrollment Poland | 61 Participants | 32 Participants | 93 Participants |
| Region of Enrollment Romania | 55 Participants | 34 Participants | 89 Participants |
| Region of Enrollment Serbia | 11 Participants | 4 Participants | 15 Participants |
| Region of Enrollment Spain | 28 Participants | 8 Participants | 36 Participants |
| Region of Enrollment United Kingdom | 4 Participants | 5 Participants | 9 Participants |
| Region of Enrollment United States | 21 Participants | 6 Participants | 27 Participants |
| Sex: Female, Male Female | 110 Participants | 49 Participants | 159 Participants |
| Sex: Female, Male Male | 161 Participants | 78 Participants | 239 Participants |
| Spirometry FEV1 | 2.842 Liters STANDARD_DEVIATION 0.7538 | 2.838 Liters STANDARD_DEVIATION 0.853 | 2.841 Liters STANDARD_DEVIATION 0.7831 |
| Spirometry FEV1/FVC | 77.6 Ratio % STANDARD_DEVIATION 6.23 | 76.8 Ratio % STANDARD_DEVIATION 6.5 | 77.3 Ratio % STANDARD_DEVIATION 6.32 |
| Spirometry FVC | 3.665 Liters STANDARD_DEVIATION 0.9203 | 3.696 Liters STANDARD_DEVIATION 1.0497 | 3.675 Liters STANDARD_DEVIATION 0.9622 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 271 | 0 / 127 |
| other Total, other adverse events | 192 / 271 | 64 / 127 |
| serious Total, serious adverse events | 42 / 271 | 13 / 127 |
Outcome results
Primary
Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second [FEV1]
To characterize the pulmonary safety, as assessed by spirometry (forced expiratory volume in 1 second \[FEV1\], over a 12 month period.
Time frame: Month 12 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CVT-301 | Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second [FEV1] | 2.778 Liters | Standard Deviation 0.7309 |
| Observational Cohort | Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second [FEV1] | 2.767 Liters | Standard Deviation 0.8419 |
Primary
Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second / Forced Vital Capacity Ratio.
To characterize the pulmonary safety, as assessed by spirometry (forced expiratory volume in 1 second / forced vital capacity ratio).
Time frame: Month 12 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CVT-301 | Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second / Forced Vital Capacity Ratio. | 78.1 Ratio (%) | Standard Deviation 6.04 |
| Observational Cohort | Pulmonary Safety Assessed by Forced Expiratory Volume in 1 Second / Forced Vital Capacity Ratio. | 76.1 Ratio (%) | Standard Deviation 6.4 |
Primary
Pulmonary Safety Assessed by Forced Vital Capacity [FVC].
To characterize the pulmonary safety, as assessed by spirometry (forced vital capacity).
Time frame: Month 12 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CVT-301 | Pulmonary Safety Assessed by Forced Vital Capacity [FVC]. | 3.558 Liters | Standard Deviation 0.8987 |
| Observational Cohort | Pulmonary Safety Assessed by Forced Vital Capacity [FVC]. | 3.642 Liters | Standard Deviation 1.0687 |
Secondary
Diffusion Capacity of the Lungs for Carbon Monoxide (DLco).
To describe the effects of CVT-301 on diffusion capacity of the lungs for carbon monoxide (DLco) over a 12-month period.
Time frame: Month 12 reported
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CVT-301 | Diffusion Capacity of the Lungs for Carbon Monoxide (DLco). | 23.273 mL/min/mmHg | Standard Deviation 6.0025 |
| Observational Cohort | Diffusion Capacity of the Lungs for Carbon Monoxide (DLco). | 23.473 mL/min/mmHg | Standard Deviation 7.0848 |