Study to Evaluate DNL201 in Subjects With Parkinson's Disease

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL201 in Subjects With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: DNL201
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DNL201 low dose<br> | Drug: DNL201<br>* Oral repeating dose<br>|
| Experimental: DNL201 high dose<br> | Drug: DNL201<br>* Oral repeating dose<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201 |  | 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 | 
| Pharmacodynamic measure of pS935 in whole blood and/or PBMCs |  | Randomization to Day 28 | 
| Pharmacodynamic measure of pRab10 in PBMCs |  | Randomization to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LRRK2, Parkinson's Disease, Movement Disorders