Study to Evaluate DNL201 in Subjects With Parkinson's Disease

Phase 1

Completed

• Conditions: Parkinson Disease
• Interventions: Drug: Placebo; Drug: DNL201

• Registration Number: NCT03710707
• Lead Sponsor: Denali Therapeutics Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-15
• Study First Submitted QC: 2018-10-16
• Study First Posted: 2018-10-18
• Study Start: 2018-12-04
• Primary Completion: 2019-12-06
• Study Completion: 2019-12-06
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-08
• Last Update Posted: 2020-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
DNL201 high dose	DNL201	-
DNL201 low dose	DNL201	-

Primary Outcome Measures

Name	Time	Method
Number of Subjects with laboratory test abnormalities	Randomization to Day 42
Number of Subjects with electrocardiogram (ECG) abnormalities	Randomization to Day 42
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Randomization to Day 42
Number of Subjects with vital sign abnormalities	Randomization to Day 42
Number of Subjects with clinically significant neurological examination abnormalities	Randomization to Day 42

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic measure of maximum observed plasma concentration (Cmax) 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
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
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

Trial Locations

Locations (1)

Clinical Site(s); 🇺🇸 Spokane, Washington, United States