Parkinson Disease
Conditions
Keywords
LRRK2, Parkinson's Disease, Movement Disorders
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL201 in subjects with Parkinson's disease.
Interventions
DRUGDNL201
Oral repeating dose
DRUGPlacebo
Oral repeating dose
Sponsors
Denali Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Body mass index (BMI) between 18 and 35.0 kg/m2, inclusive * Clinical diagnosis of Parkinson's disease meeting UK Brain Bank criteria and H&Y Stage I, II, or III. * sPD subgroup without a LRRK2 mutation; PD LRRK2 subgroup with LRRK2 mutation * Screening dopamine transporter (DAT) SPECT scan with a DAT deficit consistent with Parkinson's disease * Able to hold Parkinson's disease medications 8 hours (overnight) prior to specific study assessments Key
Exclusion criteria
* Any history of clinically significant asthma, chronic obstructive pulmonary disease, or emphysema within 5 years of screening, or other clinically significant pulmonary disease within 6 months of screening * Abnormal Vitals including Respiratory Rate, Body Temperature, and Blood Pressure * Pulmonary Function Tests (PFTs) (FVC \<60% predicted, FEV1 \<50% predicted, FEV1:FVC ratio \<0.6, DLCO \<70% predicted) * Clinically significant neurologic disorder other than Parkinson's disease, including history of stroke, cognitive impairment, seizure within 5 years of screening, or head trauma with loss of consciousness within 6 months of screening * Montreal Cognitive Assessment (MoCA) score of \<24 at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Randomization to Day 42 |
| Number of Subjects with laboratory test abnormalities | Randomization to Day 42 |
| Number of Subjects with vital sign abnormalities | Randomization to Day 42 |
| Number of Subjects with electrocardiogram (ECG) abnormalities | Randomization to Day 42 |
| Number of Subjects with clinically significant neurological examination abnormalities | Randomization to Day 42 |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic measure of pS935 in whole blood and/or PBMCs | Randomization to Day 28 |
| Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201 | Randomization to Day 28 |
| Pharmacodynamic measure of pRab10 in PBMCs | Randomization to Day 28 |
| Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL201 | Randomization to Day 28 |
| Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL201 | Randomization to Day 28 |
| Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL201 | Randomization to Day 28 |
| Pharmacokinetic measure of CSF concentrations of DNL201 | Randomization to Day 28 |
Countries
United States
Outcome results
None listed