Clinical trial NCT03887884: Pharmacokinetic Study of CVT-301 (Levodopa Inhalation Powder)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Lead sponsor: Acorda Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-03-25
Enrollment: 23
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: 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.
timeFrame: 4 days, 3 nights
measure: 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.
timeFrame: 4 days, 3 nights
measure: 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.
timeFrame: 4 days, 3 nights
measure: 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.
timeFrame: 4 days, 3 nights
Secondary outcomes:
measure: Columbia-Suicide Severity Rating Scale (C-SSRS).
timeFrame: 4 days, 3 nights
measure: Incidence of adverse events.
timeFrame: 4 days, 3 nights
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Acorda Site #1003
state: California
city: Hallandale Beach
country: United States
facility: Acorda Site #1005
state: Florida
city: Orlando
country: United States
facility: Acorda Site #1002
state: Florida
city: Atlanta
country: United States
facility: Acorda Site #1004
state: Georgia
city: Farmington Hills
country: United States
facility: Acorda Site #1001
state: Michigan
Study officials:
affiliation: Acorda Therapeutics
name: Charles Oh, MD
role: STUDY_DIRECTOR
References:
citation: 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.