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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Carbidopa; Drug: CVT-301 (levodopa inhalation powder); Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Site 002
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Site 001
  • Texas
    • Dallas, Texas, United States, 75247
      • Site 003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CVT-301 then Placebo (AB); 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: Carbidopa; Administered orally according to the carbidopa dosing schedule.; Other Names: Lodosyn ®; Drug: CVT-301 (levodopa inhalation powder); 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.; Other: Placebo; Placebo of CVT-301 is administered in the same way as the investigational product, except that it does not contain l-dopa.
EXPERIMENTAL: Placebo then CVT-301 (BA); 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: Carbidopa; Administered orally according to the carbidopa dosing schedule.; Other Names: Lodosyn ®; Drug: CVT-301 (levodopa inhalation powder); 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.; Other: Placebo; Placebo of CVT-301 is administered in the same way as the investigational product, except that it does not contain l-dopa.

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Acorda Therapeutics

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (ACTUAL): March 1, 2016
• Study Completion (ACTUAL): May 1, 2016

Study Registration Dates

• First Submitted: December 11, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (ESTIMATE): December 17, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): June 13, 2016
• Last Update Submitted That Met QC Criteria: June 10, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa
• Other Study ID Numbers: CVT-301-008