Idiopathic Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, Motor fluctuations, levodopa, inhaled drugs, OFF episodes
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.
Interventions
DRUGCVT-301
Sponsors
Acorda Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 86 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | 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. | 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). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes. | 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. | 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. |
Countries
Canada, Czechia, Poland, Spain, United States
Participant flow
Pre-assignment details
Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| CVT-301 Low Dose 60 mg (two capsules of 30 mg) of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration
CVT-301 | 153 |
| CVT-301 High Dose 84 mg (two capsules of 42 mg) of levodopa inhalational powder used up to 5 times/day for OFF episodes for 12 months duration
CVT-301 | 159 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 15 |
| Overall Study | Lack of Efficacy | 4 | 6 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Other - Miscellaneous | 4 | 6 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 37 | 19 |
Baseline characteristics
| Characteristic | CVT-301 Low Dose | CVT-301 High Dose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 82 Participants | 79 Participants | 161 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 80 Participants | 151 Participants |
| Age, Continuous | 63.9 years STANDARD_DEVIATION 8.76 | 62.9 years STANDARD_DEVIATION 8.34 | 63.4 years STANDARD_DEVIATION 8.55 |
| BMI | 27.65 kg/m^2 STANDARD_DEVIATION 4.82 | 27.59 kg/m^2 STANDARD_DEVIATION 4.79 | 27.62 kg/m^2 STANDARD_DEVIATION 4.797 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 147 Participants | 150 Participants | 297 Participants |
| Region of Enrollment Canada | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Czechia | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Poland | 39 participants | 45 participants | 84 participants |
| Region of Enrollment Spain | 5 participants | 6 participants | 11 participants |
| Region of Enrollment United States | 100 participants | 101 participants | 201 participants |
| Sex: Female, Male Female | 43 Participants | 40 Participants | 83 Participants |
| Sex: Female, Male Male | 110 Participants | 119 Participants | 229 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 153 | 0 / 159 |
| other Total, other adverse events | 81 / 153 | 69 / 159 |
| serious Total, serious adverse events | 22 / 153 | 13 / 159 |
Outcome results
Primary
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.
Time frame: Change from baseline at 52 weeks
Population: Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV3 (Week 12) | -0.2 Ratio % | Standard Deviation 3.35 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV5 (Week 36) | -0.3 Ratio % | Standard Deviation 2.75 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV4 (Week 24) | -0.3 Ratio % | Standard Deviation 3.64 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV6 (Week 52) | -0.2 Ratio % | Standard Deviation 3.36 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | Baseline | 77.2 Ratio % | Standard Deviation 5.24 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV6 (Week 52) | -0.7 Ratio % | Standard Deviation 3.51 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | Baseline | 77.2 Ratio % | Standard Deviation 6 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV3 (Week 12) | -0.3 Ratio % | Standard Deviation 2.89 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV4 (Week 24) | -0.3 Ratio % | Standard Deviation 2.91 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for (FEV1/FVC). | TV5 (Week 36) | -0.3 Ratio % | Standard Deviation 3.02 |
Primary
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.
Time frame: Change from baseline at 52 weeks
Population: Safety Population - Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV3 (Week 12) | -0.064 Liter | Standard Deviation 0.2575 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV5 (Week 36) | -0.089 Liter | Standard Deviation 0.3051 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV6 (Week 52) | -0.106 Liter | Standard Deviation 0.2866 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV4 (Week 24) | -0.053 Liter | Standard Deviation 0.271 |
| CVT-301 DL1 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | Baseline | 3.840 Liter | Standard Deviation 0.9047 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV6 (Week 52) | -0.089 Liter | Standard Deviation 0.2747 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | Baseline | 4.045 Liter | Standard Deviation 0.9811 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV3 (Week 12) | -0.086 Liter | Standard Deviation 0.2667 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV4 (Week 24) | -0.062 Liter | Standard Deviation 0.2688 |
| CVT-301 DL2 | Pulmonary Safety for CVT-301 Change From Baseline for FVC. | TV5 (Week 36) | -0.050 Liter | Standard Deviation 0.2659 |
Primary
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.
Time frame: Change from baseline at 52 weeks
Population: Safety population - Altogether, 325 patients were randomized and 312 patients received at least 1 dose of study drug and were included in the Safety Population. Thirteen patients were randomized but did not receive study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CVT-301 DL1 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV3 (Week 12) | -0.059 Liters | Standard Deviation 0.2321 |
| CVT-301 DL1 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV5 (Week 36) | -0.076 Liters | Standard Deviation 0.2155 |
| CVT-301 DL1 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV4 (Week 24) | -0.057 Liters | Standard Deviation 0.1999 |
| CVT-301 DL1 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV6 (Week 52) | -0.086 Liters | Standard Deviation 0.2238 |
| CVT-301 DL1 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | Baseline | 2.957 Liters | Standard Deviation 0.6995 |
| CVT-301 DL2 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV6 (Week 52) | -0.097 Liters | Standard Deviation 0.223 |
| CVT-301 DL2 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | Baseline | 3.117 Liters | Standard Deviation 0.7735 |
| CVT-301 DL2 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV3 (Week 12) | -0.078 Liters | Standard Deviation 0.2108 |
| CVT-301 DL2 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV4 (Week 24) | -0.058 Liters | Standard Deviation 0.2136 |
| CVT-301 DL2 | Pulmonary Safety of CVT-301 Change From Baseline for FEV1. | TV5 (Week 36) | -0.052 Liters | Standard Deviation 0.2096 |
Secondary
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.
Time frame: Change from baseline through 12 months duration of outpatient use
Population: ITT - (Intent-to-Treat) Population. Patients who discontinue the study prior to a treatment visit are not included in the analysis for that treatment visit. Therefore, the number of patients decreases with each successive treatment visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CVT-301 DL1 | Change From Baseline in OFF Time. | TV3 (Week 12) | -0.23 Hours | Standard Error 0.232 |
| CVT-301 DL1 | Change From Baseline in OFF Time. | TV5 (Week 36) | -0.49 Hours | Standard Error 0.238 |
| CVT-301 DL1 | Change From Baseline in OFF Time. | TV4 (Week 24) | -0.65 Hours | Standard Error 0.235 |
| CVT-301 DL1 | Change From Baseline in OFF Time. | TV6 (Week 52) | -0.70 Hours | Standard Error 0.239 |
| CVT-301 DL1 | Change From Baseline in OFF Time. | TV2 (Week 4) | -0.33 Hours | Standard Error 0.221 |
| CVT-301 DL2 | Change From Baseline in OFF Time. | TV6 (Week 52) | -0.88 Hours | Standard Error 0.229 |
| CVT-301 DL2 | Change From Baseline in OFF Time. | TV2 (Week 4) | -0.55 Hours | Standard Error 0.217 |
| CVT-301 DL2 | Change From Baseline in OFF Time. | TV3 (Week 12) | -0.38 Hours | Standard Error 0.227 |
| CVT-301 DL2 | Change From Baseline in OFF Time. | TV4 (Week 24) | -0.73 Hours | Standard Error 0.227 |
| CVT-301 DL2 | Change From Baseline in OFF Time. | TV5 (Week 36) | -0.92 Hours | Standard Error 0.23 |
Secondary
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).
Time frame: At Treatment Visit - TV6 (Week 52)
Population: ITT (Intent-to-Treat) Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CVT-301 DL1 | Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes. | 78 Participants |
| CVT-301 DL2 | Count of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes. | 92 Participants |