NCT03710707
Completed
Phase 1
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
Overview
- Phase
- Phase 1
- Intervention
- DNL201
- Conditions
- Parkinson Disease
- Sponsor
- Denali Therapeutics Inc.
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
DNL201 low dose
Intervention: DNL201
DNL201 high dose
Intervention: DNL201
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Randomization to Day 42
Number of Subjects with vital sign abnormalities
Time Frame: Randomization to Day 42
Number of Subjects with electrocardiogram (ECG) abnormalities
Time Frame: Randomization to Day 42
Number of Subjects with laboratory test abnormalities
Time Frame: Randomization to Day 42
Number of Subjects with clinically significant neurological examination abnormalities
Time Frame: Randomization to Day 42
Secondary Outcomes
- 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)
Study Sites (1)
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