EC5026 is a fatty acid amide hydrolase (FAAH) inhibitor being developed by EicOsis for the treatment of Parkinson's disease. The STEP Study (NCT07142044) is a Phase 1 clinical trial evaluating the safety, tolerability, and pharmacokinetics of EC5026 in patients with Parkinson's disease[eicosis2024].
FAAH inhibition represents a novel approach to Parkinson's disease therapy by modulating the endocannabinoid system, which plays important roles in neuroprotection, neuroinflammation, and motor control[faahpd].
| Parameter |
Value |
| NCT Number |
NCT07142044 |
| Trial Name |
STEP Study (EC5026) |
| Phase |
Phase 1 |
| Status |
Recruiting |
| Sponsor |
EicOsis, Inc. |
| Indication |
Parkinson's Disease |
| Intervention |
EC5026 (oral) |
| Comparator |
Placebo |
| Study Start |
2025 |
| Estimated Completion |
2026 |
| Enrollment |
~40-60 patients |
The trial employs a randomized, double-blind, placebo-controlled design:
- Allocation: Randomized (escalating dose cohorts)
- Intervention: EC5026 oral tablets
- Control: Matching placebo tablets
- Duration: Multiple ascending dose (MAD) cohorts
- Follow-up: 4-week safety follow-up
Fatty acid amide hydrolase (FAAH) is the primary enzyme responsible for degrading endogenous cannabinoids (endocannabinoids) such as anandamide. By inhibiting FAAH, EC5026 increases anandamide levels in the brain, which:
- Enhances CB1 Receptor Signaling: Increased anandamide potentiates CB1 receptor activity, providing neuroprotective effects
- Reduces Neuroinflammation: Endocannabinoid signaling modulates microglial activation and reduces inflammatory cytokine production
- Provides Antioxidant Effects: Anandamide exhibits antioxidant properties that may protect dopaminergic neurons
- Modulates Motor Control: The endocannabinoid system influences basal ganglia function and motor coordination
Parkinson's disease involves progressive degeneration of dopaminergic neurons in the substantia nigra, leading to motor symptoms. FAAH inhibition may address multiple aspects of PD pathophysiology:
- Neuroprotection: Enhanced endocannabinoid signaling may protect remaining dopaminergic neurons from degeneration
- Anti-inflammatory Effects: Reduced neuroinflammation could slow disease progression
- Motor Symptom Modulation: CB1 receptor modulation may improve motor function
This mechanism differs from conventional dopamine replacement therapies by targeting the underlying disease process rather than just symptoms.
- Age 40-75 years
- Diagnosis of idiopathic Parkinson's disease (UK Brain Bank criteria)
- Disease duration 1-15 years
- Hoehn & Yahr stage 1-3
- On stable PD medication regimen for ≥4 weeks (if receiving treatment)
- MDS-UPDRS Part 3 score ≥10
- MMSE score ≥24
- Able to swallow tablets
- Willing to comply with study procedures
- Written informed consent
- Atypical parkinsonism (PSP, MSA, CBS)
- Significant cognitive impairment (MMSE <24)
- History of stroke or significant neurological disease
- Active malignancy
- Severe medical conditions (cardiovascular, hepatic, renal)
- Prior FAAH inhibitor therapy
- Known hypersensitivity to EC5026
- Pregnancy or breastfeeding
- Current participation in other clinical trials
- Substance abuse disorder
- Safety and Tolerability: Incidence and severity of adverse events
- Pharmacokinetics: Cmax, AUC, half-life of EC5026
- Pharmacodynamics: Changes in anandamide levels
- MDS-UPDRS Parts 1-3 (motor and non-motor scores)
- PDQ-39 (quality of life)
- MoCA (Montreal Cognitive Assessment)
- Biomarker analysis (inflammatory markers)
- CSF sampling (in selected cohorts)
- Neuroimaging substudy
Early to mid-stage Parkinson's disease patients who:
- Meet clinical diagnostic criteria for idiopathic PD
- Have no significant comorbidities
- Are able to complete all study assessments
The Phase 1 trial will enroll approximately 40-60 healthy volunteers and PD patients across multiple dose escalation cohorts.
Based on preclinical data and known FAAH inhibitor class effects:
- Common: Gastrointestinal symptoms (mild nausea, abdominal discomfort)
- Potential: Dizziness, fatigue
- Class Effects: Some FAAH inhibitors have shown hepatotoxicity in long-term use — close monitoring required
- Vital signs
- Laboratory tests (CBC, chemistry, liver function)
- ECG monitoring
- Adverse event assessment
EC5026 represents a disease-modifying approach through FAAH inhibition:
- Targeting Neuroprotection: Rather than just symptom relief, FAAH inhibition may protect neurons
- Anti-inflammatory: Modulation of neuroinflammation is a key therapeutic target
- Oral Administration: Small molecule approach allows for convenient dosing
| Therapy |
Type |
Route |
Phase |
Target |
| EC5026 |
Small molecule |
Oral |
Phase 1 |
FAAH (endocannabinoid) |
| Buntanetap |
Small molecule |
Oral |
Phase 3 |
Alpha-synuclein aggregation |
| Exenatide |
GLP-1 agonist |
Injection |
Phase 3 |
Neuroprotection |
| LRRK2 inhibitors |
Small molecule |
Oral |
Phase 2 |
LRRK2 kinase |
¶ Challenges and Considerations
- Phase 1 Stage: Early development — safety profile still being established
- Mechanism Validation: FAAH inhibition efficacy in PD requires clinical confirmation
- Long-term Effects: Unknown if chronic FAAH inhibition is safe
- Therapeutic Window: Optimal dosing needs to be determined
As of the latest available information: