NE3107 Activity and Safety in Patients With Parkinson's Disease Using Levodopa
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NE3107 orally administered NE3107 20 mg twice daily (BID) |
Drug: NE3107
NE3107 is an investigational orally bioavailable, blood-brain barrier permeable anti-inflammatory agent with a new mechanism of action targeting multiple mechanisms of pathology in Parkinson's disease
|
| Placebo Comparator: placebo orally administered placebo, twice daily |
Drug: placebo
Hard gelatin capsule containing only common excipients for oral formulations
|
Outcome Measures
Primary Outcome Measures
- 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) [measured on day 1, 2, 3, 14, and 28]
Unified Parkinson's disease rating scale Part III total score is the cumulative score of a 33 question assessment of disease impact on patient's ability to move, with each part scored on a scale of 0-4, with 0 being no effect of disease and 4 being severe disease. a total score of 0 indicates no disease and a total score of 132 indicates the most severe disease
- Change from baseline in the length of time during which L-dopa therapy is ineffective in reducing motor symptoms of disease (OFF time) [off time will be measured/recorded every day from day 2 to day 27]
The total sum of time in which a patient self categorizes themselves as in the "off" state determined by diary entries. 0 hours is the minimum/best score, which indicates continuous L-dopa-like activity for the 24 hour period. 24 hours is the worst score and indicates that there was no L-dopa-like benefit at any time during the 24 hour period.
- 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 [measured on day 1, 2, 3, 14, and 28]
An average score will be calculated from assessments of the Unified Parkinson's disease rating scale Part III total score, which is the cumulative score of a 33 question assessment of disease impact on patient's ability to move, with each question scored on a scale of 0-4, with 0 being no effect of disease and 4 being severe disease. a total score of 0 indicates no disease and a total score of 132 indicates the most severe disease. Scores will be collected several times during the eight hours following L-dopa and/or NE3107 administration.
- Motor disease society- Unified Parkinson's disease rating scale Part I total score [measured on day 1, 2, 3, 14, and 28]
the cumulative score of a 13 question assessment of disease impact on patient's cognitive impairment, with each question scored on a scale of 0-4, with 0 being no effect of disease and 4 being severe disease. a total score of 0 indicates no disease and a total score of 42 indicates the most severe disease. This test asks about the impact of disease on cognition, but does not directly measure cognitive capability.
- Motor disease society- Unified Parkinson's disease rating scale Part 2 total score [measured on day 1, 2, 3, 14, and 28]
the cumulative score of a 13 question assessment of disease impact on patient's Motor Aspects of Experiences of Daily Living, with each question scored on a scale of 0-4, with 0 being no effect of disease and 4 being a severe effect. a total score of 0 indicates no disease and a total score of 42 indicates the most severe disease.
- Change from baseline in the length of time during which L-dopa-like effects are felt by the patient [baseline and day 1, 2, 3, 14, and 28]
The total sum of time in which a patient self categorizes themselves as in the "on" state, with or without dyskinesia determined by diary entries. 0 hours is the minimum/worst score, which indicates no L-dopa-like activity for the 24 hour period. 24 hours is the best score and indicates that there was no L-dopa-like benefit at any time during the 24 hour period.
- change from baseline in L-dopa induced dyskinesia measured with the abnormal involuntary movement scale (AIMS) [AIMS will be measured during the 8 hour period of observation on Day 1, 2, 3, 14, and 28]
AIMS is a 12-item clinician-rated scale to assess severity of dyskinesias (orofacial movements and extremity and truncal movements) in patients taking L-dopa. Questions assess the overall severity, incapacitation, and the patient's level of awareness of the movements, and distress associated with them. Questions are scored from 0 (no symptom) to 4 (severe). the minimum total score of 0 indicates no dyskinesia and the maximum total score of 48 indicates severe dyskinesia.
- change from baseline in time to onset of L-dopa-like activity [measured on Day 1, 2, 3, 14, and 28]
Length of time from L-dopa administration to beginning of L-dopa activity producing "on-state". Patient self assessment of the time L-dopa-like activity begins after L-dopa administration. A decrease in the time to onset may shorten the time in the off-state and be considered a patient benefit. An increase in time to onset may lengthen time in the off-state and be considered a general worsening of response to treatment.
- Change from baseline in Non-Motor Symptom Assessment Scale for Parkinson Disease (NMSS) [Measured on Day 1, 2, 3, 14, and 28]
The Non-Motor Symptoms Scale (NMSS) is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The NMSS measures the severity and frequency of non-motor symptoms across nine dimensions. The scale can be used for patients at all stages of PD. For each question, scores of severity (0 to 3, with 0 being none and 3 being major source of distress) and frequency (1 to 4, 1= rarely and 4 = very frequent) are recorded and the product of the two calculated. The sum of the products yields the overall score. The minimum total score of 0 indicates no non-motor symptoms and the maximum score of 360 indicates severe disease.
- change in area under the levodopa plasma concentration vs. time curve when administered alone compared to being co-administered with NE3107 [Blood samples will be collected on Day 1, 2, 3, and 14]
the plasma concentration vs time curve for L-dopa will be calculated from the L-dopa concentration in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours after L-dopa administration on days on which NE3107 is not administered (Day 1) and three days on which NE3107 is co-administered (Day 2, 3, and 14). Changes in L-dopa area under the curve could be associated with changes in activity against motor symptoms of disease.
- Change in the maximum plasma concentration (Cmax) of levodopa when administered alone compared to being co-administered with NE3107. [Blood samples will be collected on Day 1, 2, 3, and 14]
the maximum plasma concentration for L-dopa will be determined in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours after L-dopa administration on days on which NE3107 is not administered (Day 1) and three days on which NE3107 is co-administered (Day 2, 3, and 14). Changes in L-dopa Cmax could be associated with changes in activity against motor symptoms of disease.
- The area under the NE3107 plasma concentration vs. time curve when administered alone compared to being co-administered with [Blood samples will be collected on Day 2, 3, and 14]
the plasma concentration vs time curve for NE3107 will be calculated from the NE3107 concentration in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours
- Change in the maximum plasma concentration (Cmax) of NE3107 when administered alone compared to being co-administered with L-dopa [Blood samples will be collected on Day 2, 3, and 14]
the maximum plasma concentration for NE3107 will be determined in plasma samples collected prior to dosing and at 0.5, 1, 2, 3, 4, and 8 hours after NE3107 administration
Eligibility Criteria
Criteria
Inclusion Criteria:
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Men or women at least 30 and no more 80 years of age
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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
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Stable doses of all PD medications for at least 4 weeks prior to Screening
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Carbidopa/levodopa dose of at least 300 mg daily, distributed over a minimum of 3 dosing intervals during waking hours
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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
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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:
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Surgical sterility (via vasectomy, hysterectomy, or bilateral tubal ligation) or postmenopausal status in females
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Sexual partner who is sterile or of the same sex
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Double-barrier method (any combination of physical and chemical methods)
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Intrauterine device in females not containing hormones.
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Able and willing to comply with study drug administration, scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study
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Investigational Review Board/Ethics Committee-approved consent form signed and date by the participant
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Assessed as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC)
Exclusion Criteria:
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Diagnosis of secondary or atypical parkinsonism
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Severe or disabling fluctuations or dyskinesias that would, in the opinion of the investigator, interfere with completion of the study
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Clinically significant cognitive impairment
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Clinically significant hallucinations or delusions
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Clinically significant orthostatic hypotension
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Currently active major depression as determined by BDI-II score of >19
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Previous surgical procedure for PD (Duopa, DBS, etc.)
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History of small bowel or gastric surgery
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History of clinically significant GI abnormality (inflammatory bowel disease, significant motility disorder or emesis of any cause, etc.)
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Use of long-acting levodopa formulations (Sinemet CR, ER, Rytary, etc.)
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Routine use of proton pump inhibitors or H2 blockers
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Routine use of medications that may influence gastric motility (opiates, TCA antidepressants, anticholinergics, etc.)
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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
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Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN)
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Significant renal impairment as determined by creatinine clearance (CrCL) less than or equal to 50 mL/min
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Participant has an ECG or clinical evidence of potentially unstable heart disease, including the following:
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QTcF > 470 msec females; > 450 msec males
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Complete right or left bundle branch block
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Ischemia or myocardial infarct within 1 year prior to the Screening Visit
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Clinically significant atrial or ventricular dysrhythmia; the heart must be in predominantly normal sinus rhythm
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Second- or third-degree AV block
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Heart failure of NYHA classification III or greater
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Serious cardiomyopathy or cardiac structural abnormality
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Symptomatic coronary artery or ischemic cardiac disease
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Any other cardiac condition that the Investigator feels may predispose the participant to ischemia or arrhythmia.
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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
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Medical or recreational use of marijuana or CBD within 3 months of the Screening Visit
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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
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Currently lactating or pregnant, or planning to become pregnant during the study
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Current participation in another investigational clinical study and/or receipt of any investigational drug within 90 days prior to screening
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Prior randomization into this study
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Diabetes requiring insulin treatment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rocky Mountain Movement Disorders Center | Englewood | Colorado | United States | 80113 |
| 2 | Parkinson's Disease & Movement Disorders Center Of Boca Raton | Boca Raton | Florida | United States | 33486 |
| 3 | Velocity | Hallandale Beach | Florida | United States | 33009 |
| 4 | Charter Research | Lady Lake | Florida | United States | 32159 |
| 5 | First Excellent Research Group | Miami | Florida | United States | 33172 |
| 6 | First Excellent Research | Miami | Florida | United States | 33172 |
| 7 | EZY Medical Research | Miami | Florida | United States | 33175 |
| 8 | Charter Research | Winter Park | Florida | United States | 32792 |
| 9 | Quest Research Institute | Farmington Hills | Michigan | United States | 48334 |
| 10 | Duke University | Durham | North Carolina | United States | 27705 |
| 11 | M3 Wake | Raleigh | North Carolina | United States | 27612 |
| 12 | Wake Research | Raleigh | North Carolina | United States | 27612 |
| 13 | University of Toledo | Toledo | Ohio | United States | 43614 |
| 14 | Texas Institute for Neurological Disorders | Sherman | Texas | United States | 75092 |
| 15 | Inland Northwest Research | Spokane | Washington | United States | 99202 |
Sponsors and Collaborators
- BioVie Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NM201