Parkinson Disease
Conditions
Brief summary
Single center, open-label, intra-individual dose-escalation study in subjects with mild/moderate Parkinson's Disease
Detailed description
After assessing eligibility during a screening period of up to 4 weeks, up to 6 subjects will be included. Subjects will check into the clinic one day prior to dosing (Day -1). To evaluate and compare drug exposure levels in plasma and CSF, plasma and CSF will be serially sampled over a period of 36 hours. Subjects will be discharged from the clinic on Day 5 after all required study procedures are completed and if medically justified. Subjects will return to the clinic approximately 1 week after discharge from the clinic for a follow-up visit.
Interventions
DRUGIZD174
Small molecule inhibitor of NLRP3
Sponsors
Inflazome UK Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* The subject is a man or woman aged between 45 and 75, inclusive. * Documented clinically established diagnosis of Parkinson's Disease, Hoehn & Yahr stage 1 to 3 and Montreal Cognitive Assessment greater or equal than 26. Diagnosis of Parkinson's Disease consistent wit MDS Research Criteria for the Diagnosis of Parkinson's Disease must include bradykinesia with sequence effect, and motor asymmetry (especially if no rest tremor). Diagnosis has to be made less than 3 years prior to Screening. * The subject understands the nature and purpose of the study, including possible risks and side effects, and i willing and able to comply with all compulsory stud procedures and provides signed and dated written informed consent (in accordance with local regulations) prior to any study procedures being performed.
Exclusion criteria
* The subject used any NSAIDs, steroids, colchicine or anti-IL-1 inhibitors within 7 days prior to Day 1. * The subject received any investigational drugs within 4 weeks or 5 half-lives (whichever is longer), prior to Day 1. * The subject had an active systemic infection (other than common cold) within 2 weeks prior to Day 1. * The subject has a history of severe hypersensitivity to previous drugs. * The subject has any severe, progressive or uncontrolled medical condition at Screening or on Day -1 that in the judgment of the investigator prevents the subject from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of IZD174 in plasma | Pre-dose to 36 hours post dose | Plasma PK profile following an intra-individual dose escalation of IZD174 |
| Concentration of IZD174 in cerebrospinal fluid | Pre-dose to 36 hours post dose | CSF PK profile following an intra-individual dose escalation of IZD174 |
| Ratio of IZD174 concentration in plasma to CSF | Pre-dose to 36 hours post dose | CSF to plasma concentration ratio at each time point |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inhibition of Interleukin-1 beta secretion in ex-vivo stimulated whole blood | Pre-dose to 36 hours post dose | Inhibition of IL-1 secretion by ex-vivo stimulated whole blood |
| Incidence of Treatment-Emergent Adverse Events | Day 0 to Day 10 | Safety & Tolerability as measured by incidence if Treatment-Emergent Adverse events |
Outcome results
None listed