Study to Evaluate DNL201 in Subjects With Parkinson's Disease

NCT03710707 | Completed Phase 1 FDA Drug

• 1 other identifier: DNLI-B-0002
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 7

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.

Conditions

Parkinson Disease

Keywords

LRRK2; Parkinson's Disease; Movement Disorders

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (7)

• 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

Study Arms (3)

DNL201 low dose

EXPERIMENTAL

Drug: DNL201

DNL201 high dose

EXPERIMENTAL

Drug: DNL201

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

DNL201 DRUG

Oral repeating dose

DNL201 high dose; DNL201 low dose

Placebo DRUG

Oral repeating dose

Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Denali Therapeutics Inc.: lead

Study Sites (7)

Clinical Site(s)

Long Beach, California, 90808, United States

Location

Clinical Site(s)

Aurora, Colorado, 80045, United States

Location

Clinical Site(s)

Miami, Florida, 33143, United States

Location

Clinical Site(s)

Orlando, Florida, 32806, United States

Location

Clinical Site(s)

Farmington Hills, Michigan, 48334, United States

Location

Clinical Site(s)

Philadelphia, Pennsylvania, 19104, United States

Location

Clinical Site(s)

Spokane, Washington, 99202, United States

Location

Related Publications (2)

• Maloney MT, Wang X, Ghosh R, Andrews SV, Maciuca R, Masoud ST, Agam M, Caprioli RM, Astarita G, Bondar VV, Chen J, Chiu CL, Davis SS, Ho AC, Nguyen HN, Propson NE, Reyzer ML, Davis OB, Deen MC, Zhu S, Di Paolo G, Vocadlo DJ, Estrada AA, de Vicente J, Lewcock JW, Arguello A, Suh JH, Huntwork-Rodriguez S, Henry AG. LRRK2 kinase activity regulates Parkinson's disease-relevant lipids at the lysosome. Mol Neurodegener. 2025 Aug 6;20(1):89. doi: 10.1186/s13024-025-00880-7.

  PMID: 40770658 DERIVED

• Joshi D, Kulkarni M, Parekh P, Shah S, Greig NH, Acharya S. Targeting protein kinases in Parkinson's disease: the emerging role of phytoconstituents. Nutr Neurosci. 2025 Dec;28(12):1532-1563. doi: 10.1080/1028415X.2025.2531356. Epub 2025 Jul 18.

  PMID: 40680102 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Movement Disorders

Interventions

2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propanenitrile

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 18, 2018
• Study Start: December 4, 2018
• Primary Completion: December 6, 2019
• Study Completion: December 6, 2019
• Last Updated: January 13, 2020

Record last verified: 2020-01

Locations

US (7)