Pharmacokinetic Study of CVT-301 (Levodopa Inhalation Powder)

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: CVT-301; Drug: Sinemet

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Acorda Site #1003
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Acorda Site #1005
    • Orlando, Florida, United States, 32806
      • Acorda Site #1002
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Acorda Site #1004
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Acorda Site #1001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Acorda Therapeutics
• Investigators: Study Director: Charles Oh, MD, Acorda Therapeutics

Publications and helpful links

General Publications

• Safirstein BE, Ellenbogen A, Zhao P, Henney HR 3rd, Kegler-Ebo DM, Oh C. Pharmacokinetics of Inhaled Levodopa Administered With Oral Carbidopa in the Fed State in Patients With Parkinson's Disease. Clin Ther. 2020 Jun;42(6):1034-1046. doi: 10.1016/j.clinthera.2020.04.004. Epub 2020 May 29.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Actual): June 28, 2019
• Study Completion (Actual): June 28, 2019

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (Actual): March 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 2, 2019
• Last Update Submitted That Met QC Criteria: August 1, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Dopamine Agonists; Dopamine Agents; Adjuvants, Immunologic; Antiparkinson Agents; Anti-Dyskinesia Agents; Carbidopa, levodopa drug combination
• Other Study ID Numbers: CVT-301-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No