Primary objective:To investigate the pharmacokinetics (PK) of IZD174 in plasma and CSF of subjects with Parkinson*s Disease.Secondary objective:To investigate the pharmacodynamics (PD) of IZD174 in plasma of subjects with Parkinson*s Disease as…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following ratios will be derived to evaluate to which extent IZD174
penetrates into the brain:
CSF to plasma concentration ratios (CCSF:Cp) at each time point;
CSF to plasma AUC ratio for each dose level (AUC0-8,CSF/AUC0-8,plasma and
AUC0-t,CSF/AUC0-t,plasma [for the 3rd dose only]) and within three dose levels
(AUC0-t,CSF/AUC0-t,plasma).
The following are defined as Plasma and CSF PK parameters for IZD174 within
three dose levels (calculated using a non-compartmental model): Maximum
concentration (Cmax);
Time to Cmax (Tmax);
Area under the concentration-time curve (AUC) from time of 1st dosing (zero) to
time t of the last measured concentration above the limit of quantification
(AUC0-t);
Area under the concentration-time curve from time of 1st dosing (zero) to
infinity (AUC0-inf);
Total body clearance (CL/F) and volume of distribution (Vz/F).
Secondary outcome
The PD parameter NLRP3 inhibition in whole blood (ex vivo stimulated).
Safety parameters include AEs, physical examination, neurological examination,
clinical laboratory values, vital signs, and 12-lead ECG.
Background summary
IZD174 is a novel NLRP3 inhibitor and has been shown in non-clinical studies to
cross the blood-brain barrier making it a candidate drug to treat
neurodegenerative diseases such as Parkinson*s Disease. IZD174 has been studied
within a phase I study in healthy subjects where a linear increase of plasma
exposure with dose was noted. Safety and tolerability was unremarkable with
doses up to 300 mg bid for seven days.
This study aims to evaluate the pharmacokinetics and pharmacodynamics in plasma
and CSF in Parkinson*s patients. In particular, it is of interest to evaluate
the correlation of plasma and CSF exposure in order to generate a PK/PD model
allowing to deliver a drug dosing rationale for a subsequent phase II
safety/efficacy study in Parkinson*s patients.
After assessing eligibility during a screening period of up to 4 weeks, 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 released
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 release from the
clinic for a follow-up visit.
Study objective
Primary objective:
To investigate the pharmacokinetics (PK) of IZD174 in plasma and CSF of
subjects with Parkinson*s Disease.
Secondary objective:
To investigate the pharmacodynamics (PD) of IZD174 in plasma of subjects with
Parkinson*s Disease as assessed by ex-vivo LPS+nigericin cell stimulation of
whole blood.
To assess the safety and tolerability of IZD174 in subjects with Parkinson*s
Disease.
Study design
Single center, open-label, intra-individual dose-escalation study in subjects
with mild/moderate Parkinson*s Disease.
Intervention
IZD174 as 10 mg, 50 mg and 150 mg capsules
Study burden and risks
There are no distinct benefits for participating in this study. Your
participation will provide information about the study drug. This might benefit
others in the future. Disadvantage of participation in the study may be the
discomforts of the tests performed in the study and the occurrence of side
effects
88 Harcourt Street 88 Harcourt Street
Dublin D02DK18
IE
88 Harcourt Street 88 Harcourt Street
Dublin D02DK18
IE
Listed location countries
Age
Inclusion criteria
The subject is a man or woman aged between 45 and 69, 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 with 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.
Patients that receive treatment for Parkinson*s Disease should be on a stable
dose level and regimen for at least 14 days prior to study drug administration
and should have the intention to stay on this regimen throughout the study.
The subject understands the nature and purpose of the study, including possible
risks and side effects, and is willing and able to comply with all compulsory
study 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004960-23-NL |
| CCMO | NL72184.056.20 |