Clinical trial NCT03710707: Study to Evaluate DNL201 in Subjects With Parkinson's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Keywords: LRRK2
Parkinson's Disease
Movement Disorders
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-18
Enrollment: 29
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Randomization to Day 42
measure: Number of Subjects with laboratory test abnormalities
timeFrame: Randomization to Day 42
measure: Number of Subjects with vital sign abnormalities
timeFrame: Randomization to Day 42
measure: Number of Subjects with electrocardiogram (ECG) abnormalities
timeFrame: Randomization to Day 42
measure: Number of Subjects with clinically significant neurological examination abnormalities
timeFrame: Randomization to Day 42
Secondary outcomes:
measure: Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201
timeFrame: Randomization to Day 28
measure: Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL201
timeFrame: Randomization to Day 28
measure: Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL201
timeFrame: Randomization to Day 28
measure: Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL201
timeFrame: Randomization to Day 28
measure: Pharmacokinetic measure of CSF concentrations of DNL201
timeFrame: Randomization to Day 28
measure: Pharmacodynamic measure of pS935 in whole blood and/or PBMCs
timeFrame: Randomization to Day 28
measure: Pharmacodynamic measure of pRab10 in PBMCs
timeFrame: Randomization to Day 28
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Clinical Site(s)
state: California
city: Aurora
country: United States
facility: Clinical Site(s)
state: Colorado
city: Miami
country: United States
facility: Clinical Site(s)
state: Florida
city: Orlando
country: United States
facility: Clinical Site(s)
state: Florida
city: Farmington Hills
country: United States
facility: Clinical Site(s)
state: Michigan
city: Philadelphia
country: United States
facility: Clinical Site(s)
state: Pennsylvania
city: Spokane
country: United States
facility: Clinical Site(s)
state: Washington
Study officials:
References: