Parkinson's Disease (PD)
Conditions
Keywords
EC5026, Parkinson's Disease, Soluble Epoxide Hydrolase, sEH, Soluble Epoxide Hydrolase inhibitor
Brief summary
The goal of this clinical trial is to learn if the oral drug candidate EC5026 is safe and targets the correct pathways to treat Parkinson's Disease in adults. It will also learn about the levels of drug that are achieved in blood and in the fluid surrounding the brain (spinal fluid). The main questions it aims to answer are: * Is EC5026 safe in adults with Parkinson's Disease? * What are the levels of EC5026 achieved after oral administration for 28 days? * What molecules or pathways does EC5026 target, and to what extent? In addition, although it is not one of the primary aims of the study, this clinical trial will also explore if oral administration of EC5026 improves the symptoms of Parkinson's Disease. Researchers will compare EC5026 to a placebo (a look-alike substance that contains no drug). Participants will: * Take EC5026 or a placebo every day for 28 consecutive days * Visit the clinic for frequent checkups, blood tests, spinal fluid tests, and questionnaires
Detailed description
This is a double-blind, randomized, placebo-controlled Phase 1b multiple ascending dose (MAD) study to be conducted in adult male and female participants with Parkinson's Disease. The aim is to evaluate the safety, pharmacokinetics (PK), target engagement, and exploratory efficacy, of 2 ascending dose regimens of oral EC5026 in participants with Parkinson's Disease. The study drug, EC5026, is an orally bioavailable inhibitor of an enzyme, soluble epoxide hydrolase (sEH), that is being developed as a first-in-class anti-inflammatory agent. Inhibiting sEH maintains concentrations of bioavailable polyunsaturated fatty acid epoxides, known as epoxy fatty acids (EpFAs). EpFAs are potent, endogenous fatty acids that are highly produced in areas of damaged and inflamed tissue but are rapidly metabolized by sEH in vivo. Therefore, selective inhibition of sEH prolongs and enhances the anti-inflammatory activity of EpFAs. Several studies have identified the sEH enzyme as a potential therapeutic target for modulating neuroinflammatory responses in PD.
Interventions
Oral soluble epoxide hydrolase inhibitor
DRUGPlacebo
Matching oral placebo
Sponsors
EicOsis Human Health Inc.
University of California, Davis
Michael J. Fox Foundation for Parkinson's Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This study will consist of two independent dose cohorts, Cohort 1 and Cohort 2. Each cohort will enroll eighteen (9) unique participants. In each cohort, 9 adults with Parkinson's Disease will be randomized to receive EC5026 or a matching placebo (2:1 randomization ratio). EC5026 and placebo will be administered orally in tablets, once daily, for 28 consecutive days. In Cohort 1, study participants will receive a daily dose of 2 mg of EC5026 or matching placebo; in Cohort 2, study participants will receive a daily dose of 4 mg of EC5026 or matching placebo. Dosing will be inpatient for the first 4 doses (facility discharge on Day 4 of the study period) and outpatient thereafter. There will be a 28 day follow up period after receiving the last dose of EC5026 or placebo.
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Adult males and females, 50 to 80 years of age (inclusive) at the time of Screening. 2. Able to understand the consent form, and to provide voluntary written informed consent. 3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study. 4. Confirmed diagnosis of idiopathic Parkinson's Disease according to 2015 Movement Disorder Society (MDS) clinical diagnostic criteria. 5. Off state Hoehn \& Yahr below Stage 3 at the time of Screening. 6. Participants must be on stable doses of L-dopa with or without other adjunctive PD therapy for at least 30 days prior to enrollment. Doses should be expected to remain stable for the duration of the study. 7. Participants must be in overall stable condition, as determined by pre-study medical history, physical examination, clinical laboratory tests, and 12 lead ECG measurements. 8. Participants must have normal or not clinically significant clinical laboratory test results, as determined by the study investigator, including coagulation panel, blood cell counts, comprehensive metabolic panel analytes, and creatinine clearance (60 cm3/min or greater). Clinical laboratory tests results that are consistent with known, stable comorbidities will be allowed as long as the comorbidities do not represent an
Exclusion criteria
per se. 9. Participants must have a negative urinary drug screen (UDS) for illicit drugs and a negative alcohol breath test. 10. Abstention from use of other investigative or non-approved drugs for the duration of the trial 11. Male participants who are not surgically sterile (vasectomized) and their female sexual partners must agree to use contraception during the study period and for 2 months after receiving the last dose of study drug. 12. Male participants must not donate sperm during the study and for 12 months after receiving the last dose of study drug. 13. Female participants must be non-pregnant, non-lactating, and either postmenopausal for at least 1 year, or surgically sterile (bilateral tubal ligation, 'clipping or tying tubes,' or hysterectomy) for at least 3 months, or they must agree to use two forms of highly effective contraception method (less than 1 pregnancy per 100 people using the method for one year) from 28 days and/or their last confirmed menstrual period prior to study enrollment (whichever is longer) until 2 months after receiving the last dose of study drug. Postmenopausal status will be defined as follows: minimum 1 year; amenorrhea duration of 12 consecutive months and a serum FSH value \>40 IU/L; postmenopausal status must be confirmed by an FSH test at Screening). Highly effective contraception methods include: Intra-uterine device (IUD) containing either copper or levonorgestrel (e.g., Mirena®), and/or barrier methods of contraception, including condoms (external or internal) and diaphragm ('cap'). Hormonal methods of contraception (with the exception of hormonal IUD) are not permitted within this study. Female participants will refrain from using hormonal contraceptives for at least 28 days prior to study entry until the end of the study period. Participants/Participant's partner(s) must also use a barrier form of contraception, from the first dose of study drug through until 2 months after the last dose. For all females of childbearing potential, the pregnancy test result must be negative at Screening and Pre-Study Baseline (Day -1). 14. Participants must be able to speak, read, and understand English sufficiently to allow comprehension and completion of all study assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAE) [Safety and Tolerability] | 56 days | All AEs reported or observed during the study will be recorded on the electronic case report forms (eCRF). Information to be collected includes drug treatment, type of event, time of onset, dosage, investigator-specified assessment of severity and relationship to study drug, time of resolution of the event, seriousness, any required treatment or evaluations, and outcome. Any AEs resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to concurrent medications, or progression of disease states must also be reported. All AEs will be followed until they are resolved, stable, or judged by the investigator to be not clinically significant. The Medical Dictionary for Regulatory Activities will be used to code all AEs. |
Countries
United States
Contacts
CONTACTWilliam K Schmidt, PhD
STUDY_DIRECTORWilliam K Schmidt, PhD
EicOsis Human Health Inc.
PRINCIPAL_INVESTIGATORLin Zhang, MD, PhD
UC Davis Health
Outcome results
None listed