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

Study Overview
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Brief Summary
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This randomized, multicenter, placebo-controlled, double-blind study will evaluate the efficacy and safety of inhaled CVT 301 compared with placebo in PD patients experiencing motor response fluctuations (OFF phenomena) as an outpatient (i.e., at home) and in the clinic. Patients who successfully complete this study will be eligible to enroll into a 12 month treatment extension (CVT-301-004E) study.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Efficacy and Safety of CVT 301 (Levodopa Inhalation Powder) in Parkinson's Disease Patients With Motor Response Fluctuations (OFF Phenomena) (SPAN-PD™)

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: CVT-301 Low Dose
* Drug: CVT-301 High Dose
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic Parkinson's Disease (PD) diagnosed between the ages of 30 and 85 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 LD dose <1600 mg/day; Able to perform a spirometry maneuver in the ON and OFF states; Normal cognition confirmed by MMSE score ≥25 Exclusion Criteria: Pregnant or lactating females; Previous surgery for PD or plan to have stereotactic surgery during the study period; 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 contraindication to performing routine spirometry.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVT-301 Low Dose<br>Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 3 months duration | Drug: CVT-301 Low Dose<br> <br> * Other names: Inhaled levodopa;|
| Experimental: CVT-301 High Dose<br>Capsules of levodopa inhalational powder used up to 5 times/day for OFF episodes for 3 months duration | Drug: CVT-301 High Dose<br> <br> * Other names: Inhaled levodopa;|
| Placebo Comparator: Placebo<br>Capsules of inhalation-grade lactose used up to 5 times/day for OFF episodes for 3 months duration. | Other: Placebo<br> <br> * Other names: Inhalation-grade lactose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Scale (UPDRS) Part III | Primary Efficacy Analysis: Change from Predose in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at 30 Minutes post-dose at Week 12 for CVT-301 High Dose versus Placebo (ITT Population). UPDRS Part III ranges from 0 minimum to 86 maximum, with lower scores indicating better movement. Units on a scale. | 30 minutes post-dose at week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving Resolution of an OFF to an ON State Within 60 Minutes. | Examiner-assessed observation - Subject Achieving Resolution of an OFF to and ON state within 60 Minutes at TV4 - Observed | at week 12 | 
| UPDRS Part III Motor Score at 20 Minutes | Change from Predose in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at 20 Minutes post-dose at Week 12 for CVT-301 High Dose versus Placebo (ITT Population) and CVT 301 Low Dose versus Placebo. UPDRS Part III ranges from 0 minimum to 86 maximum, with lower scores indicating better movement. Units on a scale. | at week 12 | 
| Proportion of Subjects Who Improved PGIC With CVT-301 vs. Placebo at Week 12 | Patient Global impression of change at treatment visit 4 (week 12) by improvement category. Seven point Likert scale ranging from 1= much worse to 7= much better. | week 12 | 
| UPDRS Part III at 10 Min. | Change from Predose in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score at 10 Minutes post-dose at Week 12 for CVT-301 High Dose versus Placebo (ITT Population). UPDRS Part III ranges from 0 minimum to 86 maximum, with lower scores indicating better movement. Units on a scale. | week 12 | 
| PD Patient Diary | Change in total daily OFF times for 3 consecutive days prior to week 12 visit compared to 3 consecutive days prior to baseline visit. Participants recorded On or Off state in 30 minute intervals during waking hours. | post week 12 | 

 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