Pharmacokinetic Study of CVT-301 (Levodopa Inhalation Powder)

Study Overview
=================
Brief Summary
-----------------
This study will be an open-label, randomized, multi-center, 2-way crossover Pharmacokinetic PK evaluation of a single inhaled dose of CVT-301 84 mg and a single oral dose of carbidopa/levodopa CD/LD 25 mg/100 mg (Sinemet®) under fed conditions in Parkinson's Disease (PD) patients who regularly take CD/LD.

Detailed Description
-----------------
The study duration includes a screening period followed by an overnight stay in the center (4 days, 3 nights) to complete 2 treatments, including a 48-hour interval between the treatments, and a follow-up phone call 1-2 days after discharge from the center. On each of two treatment days, subjects will consume a standard high fat meal and then receive either (A) a single inhaled dose of CVT-301 or (B) a single dose of oral CD/LD followed by Pharmacokinetic (PK) sampling for 4 hours. A crossover design will be used such that each subject receives both Treatment A and Treatment B over the 2 treatment days, randomized 1:1 to the treatment sequence AB or BA.

Official Title
-----------------
Randomized, Multi-center, Open-label, Crossover Pharmacokinetic Study of CVT-301 (Levodopa Inhalation Powder) and an Oral Dose of Carbidopa/Levodopa CD/LD Under Fed Conditions in Patients With Parkinson's Disease

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: CVT-301
* Drug: Sinemet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women between the ages of 30 and 85 years, inclusive. 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. Classified as Stage 1 to 3 (in the ON state) on the modified Hoehn and Yahr scale for staging of PD severity. Stable on other non levodopa PD medications for at least 4 weeks prior to the Screening Visit. Subjects must have normal cognition as confirmed by a score of ≥ 25 on the Mini Mental State Examination (MMSE), performed in the ON state. Forced expiratory volume in one second (FEV1) ≥60% of predicted for race, age, sex, and height and FEV1/FVC (forced vital capacity) ratio ≥70%. Body Mass Index (BMI) between 18 - 32 kg/m2, inclusive. Exclusion Criteria: Any flu-like syndrome or other respiratory infections within 2 weeks prior to the Screening Visit. Chronic obstructive pulmonary disease (COPD), asthma, or other chronic respiratory disease within the last 5 years. History of any cancer in the past 5 years with the exception of successfully treated basal cell carcinoma. Narrow angle glaucoma or a history of peptic ulcer disease less than 1 year prior to screening. Previous surgery for PD (including but not limited to deep brain stimulation or cell transplantation). Current use of nicotine patch or tobacco-containing products including cigarettes, electronic cigarettes, cigars, chewing tobacco, pipe tobacco or snuff or use within 4 weeks prior to the Screening Visit, or expected use during the study. Marijuana smoking within 4 weeks prior to the Screening Visit, or expected smoking/inhalation during the study.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: It is a 2-way crossover Pharmacokinetic (PK) evaluation of a single inhaled dose of CVT-301 84 mg and a single oral dose of Carbidopa/levodopa (CD/LD) 25 mg/100 mg (Sinemet®) under fed conditions in Parkinson's Disease patients who regularly take CD/LD.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVT-301<br>Single inhaled dose of CVT-301 84 mg | Drug: CVT-301<br>* Levodopa Inhalation Powder<br>|
| Active Comparator: Sinemet<br>Single oral dose of Carbidopa/Levodopa 25 mg/100 mg | Drug: Sinemet<br>* Single oral dose of Carbidopa/Levodopa 25 mg/100 mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25 mg/100 mg (carbidopa/levodopa) in patients with Parkinson's disease. | Maximum observed plasma drug concentration (Cmax) of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25 mg/100 mg in patients with Parkinson's disease (PD) in a fed state. | 4 days, 3 nights | 
| Total plasma concentration of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25 mg/100 mg (carbidopa/levodopa) in patients with Parkinson's disease. | Area under the plasma concentration curve from time 0 to the concentration at 4 hours (AUCo-4h) of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25 mg/100 mg in patients with Parkinson's disease (PD) in a fed state. | 4 days, 3 nights | 
| Terminal half-life of a single inhaled dose of CVT-30184 mg and an oral dose of CD/LD 25 mg/100 mg (carbidopa/levodopa) in patients with Parkinson's disease. | Terminal half-life (t1/2)of a single inhaled dose of CVT-30184 and an oral dose of CD/LD 25 mg/100 mg in patients with Parkinson's disease (PD) in a fed state. | 4 days, 3 nights | 
| Time to maximum observed plasma drug concentration of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25 mg/100 mg (carbidopa/levodopa) in patients with Parkinson's disease. | Time to maximum observed plasma drug concentration (Tmax) of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25 mg/100 mg in patients with Parkinson's disease (PD) in a fed state. | 4 days, 3 nights | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Columbia-Suicide Severity Rating Scale (C-SSRS). | To evaluate the safety and tolerability of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25/100 mg) under fed conditions in PD patients using the Columbia-Suicide Severity Rating Scale (C-SSRS). The (C-SSRS) is an assessment tool that evaluates suicidal ideation and behavior. Scale range: Yes or No response to 10 questions, with minimum to maximum range of 0 to 10. Lower score represents better outcomes. Subscales not applicable. | 4 days, 3 nights | 
| Incidence of adverse events. | To evaluate the safety and tolerability of a single inhaled dose of CVT-301 84 mg and an oral dose of CD/LD 25/100 mg) under fed conditions in PD patients by accessing adverse events. | 4 days, 3 nights |