NE3107 Activity and Safety in Patients With Parkinson's Disease Using Levodopa

BioVie

Status and phase

Completed

Phase 2

Phase 1

Conditions

Parkinson Disease

Treatments

Drug: placebo

Drug: NE3107

Study type

Interventional

Funder types

Industry

Identifiers

NCT05083260

NM201

Details and patient eligibility

About

A 28-day phase 2a, double-blind, placebo-controlled (1:1), multi-center study of 20 mg NE3107, twice daily of safety, potential drug-drug interactions, and MDS-UPDRS defined activity in patients with Parkinson's disease . Study will enroll 40 patients that are currently taking immediate release levodopa/ carbidopa (IRLC) and have a practically defined early morning off-state for IRLC. Day one- baseline UPDRS and IRLC PK sampling; day 2- start NE3107 dosing, assess UPDRS during onset and NE3107 PK sampling, rescue meds as needed after 4 hours; day 3 and 14- NE3107 + IRLC UPDRS assessment and PK sampling; day 28- NE3107 + IRLC UPDRS assessments. Optional overnight stays in clinic prior to Day 1-3, 14, and 28.

Enrollment

46 patients

Sex

All

Ages

30 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Men or women at least 30 and no more 80 years of age
Diagnosis of PD consistent with UK Brain Bank Criteria or MDS Research Criteria for the Diagnosis of PD, with bradykinesia and a clear motor response to levodopa
Stable doses of all PD medications for at least 4 weeks prior to Screening
Carbidopa/levodopa dose of at least 300 mg daily, distributed over a minimum of 3 dosing intervals during waking hours
Participants must have history of motor fluctuations with reliable early-morning OFF episodes and a history of a good response to levodopa, in the judgement of the investigator
If of reproductive potential, willing and able to use a highly effective form of birth control during the study and for 30 days following last dose of study drug. Examples of highly effective forms of birth control are:
1. Surgical sterility (via vasectomy, hysterectomy, or bilateral tubal ligation) or postmenopausal status in females
2. Sexual partner who is sterile or of the same sex
3. Double-barrier method (any combination of physical and chemical methods)
4. Intrauterine device in females not containing hormones.
Able and willing to comply with study drug administration, scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study
Investigational Review Board/Ethics Committee-approved consent form signed and date by the participant
Assessed as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC)

Exclusion criteria

Diagnosis of secondary or atypical parkinsonism
Severe or disabling fluctuations or dyskinesias that would, in the opinion of the investigator, interfere with completion of the study
Clinically significant cognitive impairment
Clinically significant hallucinations or delusions
Clinically significant orthostatic hypotension
Currently active major depression as determined by BDI-II score of >19
Previous surgical procedure for PD (Duopa, DBS, etc.)
History of small bowel or gastric surgery
History of clinically significant GI abnormality (inflammatory bowel disease, significant motility disorder or emesis of any cause, etc.)
Use of long-acting levodopa formulations (Sinemet CR, ER, Rytary, etc.)
Routine use of proton pump inhibitors or H2 blockers
Routine use of medications that may influence gastric motility (opiates, TCA antidepressants, anticholinergics, etc.)
Other clinically significant medical, surgical, psychiatric, or laboratory abnormality that, in the judgment of the investigator, is likely to interfere with study compliance or assessment of safety or efficacy
1. Evidence of significant hepatic impairment according to Child-Pugh criteria, history of cirrhosis, and/or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN), evidence of ascites, hepatic encephalopathy, bilirubin greater than 2 mg/dL, albumin less than 2.0 g/dL, and INR of 1.5 and greater
Significant renal impairment as determined by creatinine clearance (CrCL) less than or equal to 50 mL/min
Participant has an ECG or clinical evidence of potentially unstable heart disease, including the following:
1. QTcF > 470 msec females; > 450 msec males
2. Complete right or left bundle branch block
3. Ischemia or myocardial infarct within 1 year prior to the Screening Visit
4. Clinically significant atrial or ventricular dysrhythmia; the heart must be in predominantly normal sinus rhythm
5. Second- or third-degree AV block
6. Heart failure of NYHA classification III or greater
7. Serious cardiomyopathy or cardiac structural abnormality
8. Symptomatic coronary artery or ischemic cardiac disease
9. Any other cardiac condition that the Investigator feels may predispose the participant to ischemia or arrhythmia.
Current (or within past 12 months) diagnosis or history of substance abuse, including alcohol (excluding nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders 5 criteria, or positive urine drug screen for tetrahydrocannabinol or any drugs that may affect participant safety or interfere with efficacy assessments
Medical or recreational use of marijuana or CBD within 3 months of the Screening Visit
Active suicidal ideation within 1 year prior to Screening Visit as determined by a positive response to Question 4 or 5 on the C-SSRS
Currently lactating or pregnant, or planning to become pregnant during the study
Current participation in another investigational clinical study and/or receipt of any investigational drug within 90 days prior to screening
Prior randomization into this study
Diabetes requiring insulin treatment
Use of potent CYP3A4 inhibitors clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, and verapamil, and potent CYP2C9 and CYP2C19 inhibitors, amiodarone, fluconazole, miconazole, piperine, fluoxetine, fluvoxamine, and ticlopidine.
History of breast cancer
History of Covid-19 (SARS-CoV-2) infection within 6-weeks prior to screening. Subjects with unresolved symptoms of Covid-19 infection or ongoing cognitive or other deficits attributable to post-Covid-19, that may affect participant safety or interfere with efficacy assessments, based on the Investigator's clinical judgment.