A Study of the Safety and Pharmacokinetics of Levodopa Following Administration of CVT 301 (Levodopa Inhalation Powder) in Adults With Asthma

Study Overview
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Brief Summary
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This study is a double-blind, randomized, placebo-controlled, 2-period, crossover study to evaluate safety and PK of 3 doses of CVT 301 levodopa (l-dopa) in adults with asthma.

Official Title
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A Phase 1 Study of the Safety and Pharmacokinetics (PK) of Levodopa Following Administration of CVT 301 (Levodopa Inhalation Powder) in Adults With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: CVT-301 (levodopa inhalation powder)
* Drug: Carbidopa
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible subjects will be men or women in good general health with a diagnosis of mild or moderate asthma; On a stable regimen of asthma medications for at least 30 days prior to screening; Body mass index (BMI) 18 to 32 kg/m2; Forced expiratory volume in one second (FEV1) ≥60% of predicted for race, age, sex, and height; FEV1/FVC (forced vital capacity) ratio ≥70%. Exclusion Criteria: More than 2 hospitalizations or emergency room visits, or more than 3 courses of systemic steroids in the past 12 months or 1 course within the past 8 weeks for respiratory illness; Asthma exacerbation within 8 weeks before screening; Unscheduled or urgent visit to any medical facility for asthma-related problems within 8 weeks before screening; History of intubation or intensive care unit admission for asthma in the past 5 years; History of chronic obstructive pulmonary disorder (COPD) requiring intermittent or continuous use of any oral or inhaled medication therapy within last 3 years; Renal impairment as defined by a calculated creatinine clearance of ≤ 80 mL/minute.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVT-301 then Placebo (AB)<br>All subjects will receive both CVT-301 and placebo in two dosing periods separated by one day. Subjects will be randomized 1:1 into sequence AB or BA [CVT-301 (A) administered first, followed by placebo (B), or the reverse order (BA)] and they will start pre-treatment of carbidopa (as Lodosyn®) administered every 8 hours until the completion of all study treatments. | Drug: CVT-301 (levodopa inhalation powder)<br>* Capsules containing l-dopa, designed to deliver ldopa to the lung using the CVT-301 inhaler. CVT-301 will be administered 3 times, 4 hours apart, and 1 hour following the administration of carbidopa.<br>Drug: Carbidopa<br>* Administered orally according to the carbidopa dosing schedule.<br>* Other names: Lodosyn ®;Other: Placebo<br>* Placebo of CVT-301 is administered in the same way as the investigational product, except that it does not contain l-dopa.<br>|
| Experimental: Placebo then CVT-301 (BA)<br>All subjects will receive both CVT-301 and placebo in two dosing periods separated by one day. Subjects will be randomized 1:1 into sequence AB or BA [CVT-301 (A) administered first, followed by placebo (B), or the reverse order (BA)] and they will start pre-treatment of carbidopa (as Lodosyn®) administered every 8 hours until the completion of all study treatments. | Drug: CVT-301 (levodopa inhalation powder)<br>* Capsules containing l-dopa, designed to deliver ldopa to the lung using the CVT-301 inhaler. CVT-301 will be administered 3 times, 4 hours apart, and 1 hour following the administration of carbidopa.<br>Drug: Carbidopa<br>* Administered orally according to the carbidopa dosing schedule.<br>* Other names: Lodosyn ®;Other: Placebo<br>* Placebo of CVT-301 is administered in the same way as the investigational product, except that it does not contain l-dopa.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulmonary function | Pulmonary function will be measured by spirometry using the guideline specified by the Third National Health and Nutrition Examination Survey (NHANES III) | within 90 min prior to dose administration and specified time points up to 24 hours after first inhalation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Adverse Events (AEs) including Serious AEs |  | up to 12 days | 
| Maximum observed plasma drug concentration (Cmax) |  | within 30 min prior to first CVT-301 dose administration and specified time points up to 24 hours post-dose | 
| Time to maximum observed plasma drug concentration (Tmax) |  | within 30 min prior to first CVT-301 dose administration and specified time points up to 24 hours post-dose | 
| Area under the concentration time curve over the dosing interval (AUC0-last) |  | within 30 min prior to first CVT-301 dose administration and specified time points up to 24 hours post-dose |