A Study of the Safety and Levodopa Pharmacokinetics Following Single Dose Administration of CVT 301 (Levodopa Inhalation Powder) in Smoking and Non-Smoking Adults

• CVT-301 (Drug): Levodopa inhalation powder, will be supplied in capsules containing levodopa (l-dopa), designed to deliver to the lung using the CVT-301 inhaler.
• Carbidopa (Drug), also known as Lodosyn ®: Administered orally according to the carbidopa dosing schedule.

Primary outcomes

• Maximum observed plasma drug concentration (Cmax) [within 30 min prior to 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 CVT-301 dose administration and specified time points up to 24 hours post-dose]
• Area under the plasma concentration versus time curve (AUC) [within 30 min prior to CVT-301 dose administration and specified time points up to 24 hours post-dose]

Secondary outcomes

• Change in pulmonary function [within 90 min prior to CVT-301 dose and at specified time points up to 24 hours post-dose]: Pulmonary function will be measured by spirometry using the guideline specified by the Third National Health and Nutrition Examination Survey (NHANES III)
• Number of subjects with Adverse Events (AEs) including Serious AEs [up to 3 days]

Sex: All, ages: 25 Years to 65 Years

Inclusion Criteria:

* Body mass index (BMI) 18 to 32 kg/m2;
* Forced expiratory volume in one second (FEV1) ≥80% of predicted for race, age, sex, and height;
* FEV1/FVC (forced vital capacity) ratio ≥70%;
* Smokers are defined as those currently smoking at least 10 cigarettes/day for at least 12 months with a positive urinary cotinine result and with no past (within 5 years) or present history of intrinsic lung disease (e.g. asthma, chronic obstructive pulmonary disease \[COPD\], chronic bronchitis, or other relevant conditions);
* Non-smokers are defined as those who never smoked or were exposed to less than 1 pack year within at least 12 months and with a negative urinary cotinine result.

Exclusion Criteria:

* Subject who is not surgically sterile or female subject who is less than 2 years postmenopausal, and who does not agree to use a highly effective birth control method during the study and up to 3 months after the last dose of investigational product;
* Any flu-like syndrome or other respiratory infections within 2 weeks prior to the Screening Visit;
* 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;
* History of syncope within the last 6 months.

• Harald Murck, MD, PhD, Study director, Acorda Therapeutics