Clinical trial NCT05083260: NE3107 Activity and Safety in Patients With Parkinson's Disease Using Levodopa
Official title: A Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetics Study in Parkinson's Disease (PD) Participants Treated With Carbidopa/Levodopa and NE3107
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Keywords: MDS-UPDRS
Lead sponsor: BioVie Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-19
Enrollment: 46
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Men or women at least 30 and no more 80 years of age
2. 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
3. Stable doses of all PD medications for at least 4 weeks prior to Screening
4. Carbidopa/levodopa dose of at least 300 mg daily, distributed over a minimum of 3 dosing intervals during waking hours
5. 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
6. 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.
7. Able and willing to comply with study drug administration, scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study
8. Investigational Review Board/Ethics Committee-approved consent form signed and date by the participant
9. Assessed as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC)

Exclusion Criteria:

1. Diagnosis of secondary or atypical parkinsonism
2. Severe or disabling fluctuations or dyskinesias that would, in the opinion of the investigator, interfere with completion of the study
3. Clinically significant cognitive impairment
4. Clinically significant hallucinations or delusions
5. Clinically significant orthostatic hypotension
6. Currently active major depression as determined by BDI-II score of \>19
7. Previous surgical procedure for PD (Duopa, DBS, etc.)
8. History of small bowel or gastric surgery
9. History of clinically significant GI abnormality (inflammatory bowel disease, significant motility disorder or emesis of any cause, etc.)
10. Use of long-acting levodopa formulations (Sinemet CR, ER, Rytary, etc.)
11. Routine use of proton pump inhibitors or H2 blockers
12. Routine use of medications that may influence gastric motility (opiates, TCA antidepressants, anticholinergics, etc.)
13. 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
14. 14) 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
15. Significant renal impairment as determined by creatinine clearance (CrCL) less than or equal to 50 mL/min
16. 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.
17. 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
18. Medical or recreational use of marijuana or CBD within 3 months of the Screening Visit
19. 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
20. Currently lactating or pregnant, or planning to become pregnant during the study
21. Current participation in another investigational clinical study and/or receipt of any investigational drug within 90 days prior to screening
22. Prior randomization into this study
23. Diabetes requiring insulin treatment
24. 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.
25. History of breast cancer
26. 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.

Primary outcomes:
measure: Change from baseline (day 1) in Motor disease society- Unified Parkinson's disease rating scale Part III total score for the patient in the "off-state" (without L-dopa for previous eight hours)
timeFrame: measured on day 1, 2, 3, 14, and 28
measure: Change from baseline in the length of time during which L-dopa therapy is ineffective in reducing motor symptoms of disease (OFF time)
timeFrame: off time will be measured/recorded every day from day 2 to day 27
measure: Change from baseline in average Motor disease society- Unified Parkinson's disease rating scale Part III total score measured over the course of 8 hours after taking L-dopa and/or NE3107
timeFrame: measured on day 1, 2, 3, 14, and 28
measure: Motor disease society- Unified Parkinson's disease rating scale Part I total score
timeFrame: measured on day 1, 2, 3, 14, and 28
measure: Motor disease society- Unified Parkinson's disease rating scale Part 2 total score
timeFrame: measured on day 1, 2, 3, 14, and 28
measure: Change from baseline in the length of time during which L-dopa-like effects are felt by the patient
timeFrame: baseline and day 1, 2, 3, 14, and 28
measure: change from baseline in L-dopa induced dyskinesia measured with the abnormal involuntary movement scale (AIMS)
timeFrame: AIMS will be measured during the 8 hour period of observation on Day 1, 2, 3, 14, and 28
measure: change from baseline in time to onset of L-dopa-like activity
timeFrame: measured on Day 1, 2, 3, 14, and 28
measure: Change from baseline in Non-Motor Symptom Assessment Scale for Parkinson Disease (NMSS)
timeFrame: Measured on Day 1, 2, 3, 14, and 28
measure: change in area under the levodopa plasma concentration vs. time curve when administered alone compared to being co-administered with NE3107
timeFrame: Blood samples will be collected on Day 1, 2, 3, and 14
measure: Change in the maximum plasma concentration (Cmax) of levodopa when administered alone compared to being co-administered with NE3107.
timeFrame: Blood samples will be collected on Day 1, 2, 3, and 14
measure: The area under the NE3107 plasma concentration vs. time curve when administered alone compared to being co-administered with
timeFrame: Blood samples will be collected on Day 2, 3, and 14
measure: Change in the maximum plasma concentration (Cmax) of NE3107 when administered alone compared to being co-administered with L-dopa
timeFrame: Blood samples will be collected on Day 2, 3, and 14
Secondary outcomes:
Other outcomes:
Locations:
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center
state: Colorado
city: Boca Raton
country: United States
facility: Parkinson's Disease & Movement Disorders Center Of Boca Raton
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity
state: Florida
city: Lady Lake
country: United States
facility: Charter Research
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: First Excellent Research Group
state: Florida
city: Miami
country: United States
facility: First Excellent Research
state: Florida
city: Miami
country: United States
facility: EZY Medical Research
state: Florida
city: Winter Park
country: United States
facility: Charter Research
state: Florida
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: New York
country: United States
facility: New York Neurology Associates
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Raleigh
country: United States
facility: M3 Wake Research
state: North Carolina
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Sherman
country: United States
facility: Texas Institute for Neurological Disorders
state: Texas
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
Study officials:
References: