Randomized Safety Study of CVT-301 Compared to an Observational Control Group

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 3, Randomized Study Investigating the Safety of CVT-301 (Levodopa Inhalation Powder) in Parkinson's Disease (PD) Patients With Motor Response Fluctuations (OFF Phenomena) Compared to an Observational Cohort Control

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: CVT-301
* Other: Observational cohort


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVT-301<br>Capsules of Levodopa Inhalational Powder (LIP) used up to 5 times per day for OFF episodes, for up to 54 weeks duration. | Drug: CVT-301<br> <br> * Other names: Inhaled levodopa;|
| Other: Observational Cohort<br>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. | Other: Observational cohort<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 12 reported | 
| Pulmonary Safety Assessed by Forced Vital Capacity [FVC]. | To characterize the pulmonary safety, as assessed by spirometry (forced vital capacity). | Month 12 reported | 
| 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). | Month 12 reported | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 12 reported | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's Disease, Motor fluctuations, levodopa, inhaled drugs, OFF episodes