Study of CVN424 in Parkinson's Disease Patients With Motor Fluctuations
- Conditions
- Parkinson Disease
- Interventions
- Drug: CVN424 High DoseDrug: PlaceboDrug: CVN424 Low Dose
- Registration Number
- NCT04191577
- Lead Sponsor
- Cerevance Beta, Inc.
- Brief Summary
This is a phase 2 study, randomized, double-blind, placebo-controlled, multicenter study of oral CVN424 at two dose levels (low-dose and high-dose) in Parkinson's disease (PD) patients with motor fluctuations.
- Detailed Description
Approximately 135 male and female subjects with Parkinson's disease, on a stable dosage of levodopa but with an average of ≥ 2 h total OFF time/day and not less than 1 h per day, will be enrolled. Following baseline safety and efficacy assessments, subjects will be randomized to receive once-daily doses of either low-dose CVN424, high-dose CVN424, or matching placebo. All subjects not randomized to placebo will initiate treatment with a low-dose of CVN424 on Day 1; the low-dose arm will continue to receive their low dose each day, while the high-dose arm will increase their daily dosage to the high-dose CVN424 beginning on Day 8 ±2 days and continuing thereafter. Study drug will be self-administered each morning as an oral suspension. Subjects will continue their other PD medications.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 136
- Male or female adult who is 30 to 80 years of age inclusive at study entry.
- Has idiopathic Parkinson's disease, Hoehn and Yahr stages 2-4, and is on a stable dosage of levodopa.
- Experiences an average of at least 2 h total OFF time/day, and at least 1 h each day, per Patient Motor Diary over 2 days during Screening assessment.
- The subject signs and dates a written informed consent form (ICF) and any required privacy authorization prior to the initiation of any study procedures.
- Has atypical parkinsonism, severe disabling dyskinesia, or severe motor fluctuations that the investigator considers likely to interfere with study participation or assessments, or history of implant for Deep Brain Stimulation.
- Poor concordance (<75%) of self-report with site rater on in-clinic Screening period Patient Motor Diary. Subjects with low concordance may be retested after further instruction, at investigator's discretion.
- Screening period Patient Motor Diary scored at-home over 2 days demonstrates unacceptable quality of the diary, with more than 4 errors per day. (Assistance from caregivers is permitted if they also will be providing assistance with home Patient Motor Diary entries for Day 15 and 27 efficacy assessments.) Subjects with more than 4 errors per day may be retested after further instruction, at investigator's discretion.
- Body mass index (BMI) at Screening <18.0 or >35.0 kg/m2, inclusive.
- Subject has evidence of Clinically significant neurologic or other disorder or impairment that, in opinion of Investigator, is reasonably expected to impact the ability of the subject to participate or to confound the study results.
- Subject has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention known to impact absorption [e.g., bariatric surgery or bowel resection]).
- Subject has a history of cancer or other malignancy, with the exception of low-grade cervical intraepithelial neoplasia, low-grade (low-risk) prostate cancer, or 5-year cancer-free survivors of basal or squamous cell carcinoma, higher-grade cervical intraepithelial neoplasia or prostate cancer.
- Has a history of human immunodeficiency virus (HIV) infection.
- Subject has a supine blood pressure outside the ranges of 80 to 160 mm Hg for systolic and 50 to 100 mm Hg for diastolic, confirmed with up to two repeat tests, at the Screening Visit; or symptomatic orthostatic hypotension, in the opinion of the investigator.
- Subject has a resting heart rate outside the range 50 to 100 bpm, confirmed with up to two repeat tests, at the Screening Visit.
- Positive urine result for illegal drugs (except cannabis) at Screening, or history of illegal drug use (except cannabis) or alcohol abuse within 1 year prior to the Screening Visit.
- Subject has received any investigational compound (defined as a drug that has not been FDA-approved) within 30 days prior to the first dose of study medication, or within 5 half-lives of the investigational compound, whichever is greater.
- Subject has, within the prior month, ingested any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table as listed in Table 2.
- Male subjects who do not agree to all the following rules: when sexually active with female partner(s) of childbearing potential during the study and for 12 weeks after the last dose of study drug: a) use an acceptable method of birth control (condom with spermicide or surgical sterilization) and b) refrain from sexual activity with female partners who do not use an acceptable method of birth control. Barrier contraception (condom with spermicide) must be used by all male subjects who were not surgically sterilized at least 90 days prior to screening. Male subjects must also agree to refrain from sperm donation during the study and until 12 weeks after the last dose of study drug.
- Female subjects who are pregnant or breastfeeding or plan to become pregnant or donate ova during the study or for 30 days after the last dose of study drug. Women of childbearing potential (WOCBP) also must be practicing an adequate method of birth control (e.g., oral or parenteral contraceptives, intrauterine device, barrier, abstinence).
- Risk of suicide according to the investigator's clinical judgment or has made a suicide attempt in the previous 3 years.
- Subject is a study site employee or an immediate family member of a study site employee
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CVN424 (High Dose) CVN424 High Dose Patients randomized to the high dose will receive low-dose CVN424 once daily from day 1 to day 7, and will then increase their dose to the full high-dose once daily beginning on day 8. Placebo Placebo Placebo to be administered once daily. CVN424 (Low Dose) CVN424 Low Dose Low dose of CVN424 to be administered once daily.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Study Drug Up to Day 35 An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as any event with onset during or after the first dose of study treatment (active or placebo).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Clinically Significant Abnormal Laboratory Parameters Up to Day 35 Blood and urine samples were collected for the analysis of laboratory parameters including clinical chemistry, hematology, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Percentage of Participants With Clinically Significant Abnormal Vital Signs Up to Day 35 Vital signs including blood pressure (systolic and diastolic blood pressure), pulse rate, body temperature, respiratory rate and weight were measured after participants rested for at least 5 minutes in supine position. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Percentage of Participants With Clinically Significant Changes 12-Lead Electrocardiogram (ECG) Findings Up to Day 35 12-lead ECG recordings including heart rate and measured PR, QRS, QT, QT interval with Fridericia's correction method (QTcF) and QT interval with Bazett's correction method (QTcB) intervals. 12-lead ECG recordings were obtained after participants rested for at least 5 minutes in supine position. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.
Change From Baseline in 2-day Average OFF Time Baseline and at Day 27 The Patient Motor Diary data (Hauser Diary) was completed by the participant to record the broad motor symptoms of pharmacodynamics. Categories included time asleep, OFF time, ON time without dyskinesia, ON time with non-troublesome dyskinesia, and ON time with troublesome dyskinesia. These diaries were collected for 24 hours on each of 2 consecutive days with records for every 30 minutes interval. The average daily OFF time was calculated from the records with reported OFF time. Baseline was defined as Day 0. Change from Baseline was defined as post Baseline minus Baseline value.
Trial Locations
- Locations (21)
NeuroTrials Research, Inc.
🇺🇸Atlanta, Georgia, United States
Prisma Health
🇺🇸Greenville, South Carolina, United States
Collaborative Neuroscience Network, LLC
🇺🇸Long Beach, California, United States
Accel Research Site - Brain and Spine Institute of Port Orange
🇺🇸Port Orange, Florida, United States
Charter Research
🇺🇸Winter Park, Florida, United States
SC3 Research - Pasadena
🇺🇸Pasadena, California, United States
Nova Clinical Research
🇺🇸Bradenton, Florida, United States
Parkinson's Disease and Movement Disorders Center of Boca Raton
🇺🇸Boca Raton, Florida, United States
Premier Clinical Research Institute
🇺🇸Miami, Florida, United States
Parkinson's Disease Treatment Center of SW Florida
🇺🇸Port Charlotte, Florida, United States
USF Parkinson's Disease and Movement Disorders Center
🇺🇸Tampa, Florida, United States
Boston Clinical Trials
🇺🇸Roslindale, Massachusetts, United States
Parkinson's Disease and Movement Disorder Center
🇺🇸Kansas City, Kansas, United States
Quest Research Institute
🇺🇸Farmington Hills, Michigan, United States
Bio Behavioral Health
🇺🇸Toms River, New Jersey, United States
M3 Wake Research
🇺🇸Raleigh, North Carolina, United States
Neurology Diagnostics Inc
🇺🇸Dayton, Ohio, United States
Optimed Research Ltd
🇺🇸Columbus, Ohio, United States
New York Neurology Associates
🇺🇸New York, New York, United States
Central Texas Neurology Consultants
🇺🇸Round Rock, Texas, United States
Inland Northwest Research, LLC
🇺🇸Spokane, Washington, United States