Study to Evaluate DNL201 in Subjects With Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03710707
• Other study ID #: DNLI-B-0002
• Status: Completed
• Phase: Phase 1
• Start date: December 4, 2018
• Est. completion date: December 6, 2019

Study information

• Verified date: January 2020
• Source: Denali Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 6, 2019
• Est. primary completion date: December 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• DNL201
Oral repeating dose
• Placebo
Oral repeating dose

Locations

Country	Name	City	State
United States	Clinical Site(s)	Aurora	Colorado
United States	Clinical Site(s)	Farmington Hills	Michigan
United States	Clinical Site(s)	Long Beach	California
United States	Clinical Site(s)	Miami	Florida
United States	Clinical Site(s)	Orlando	Florida
United States	Clinical Site(s)	Philadelphia	Pennsylvania
United States	Clinical Site(s)	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Randomization to Day 42
Primary	Number of Subjects with laboratory test abnormalities		Randomization to Day 42
Primary	Number of Subjects with vital sign abnormalities		Randomization to Day 42
Primary	Number of Subjects with electrocardiogram (ECG) abnormalities		Randomization to Day 42
Primary	Number of Subjects with clinically significant neurological examination abnormalities		Randomization to Day 42
Secondary	Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201		Randomization to Day 28
Secondary	Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL201		Randomization to Day 28
Secondary	Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL201		Randomization to Day 28
Secondary	Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL201		Randomization to Day 28
Secondary	Pharmacokinetic measure of CSF concentrations of DNL201		Randomization to Day 28
Secondary	Pharmacodynamic measure of pS935 in whole blood and/or PBMCs		Randomization to Day 28
Secondary	Pharmacodynamic measure of pRab10 in PBMCs		Randomization to Day 28