Study to Evaluate DNL201 in Subjects With Parkinson's Disease

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

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.

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