A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL151 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD), and 28-day safety study of orally administered DNL151 in healthy volunteers.

Detailed Description
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This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under Section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by Sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Official Title
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A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of DNL151 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: DNL151
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Body mass index 18.5 to 35.0 kg/m², inclusive, and body weight of at least 50.0 kg at screening In good health, determined by no clinically significant findings from medical history, physical examination, and vital sign measurements Women of non-childbearing potential and men using contraceptive measures Key Exclusion Criteria: History of clinically significant hematological, renal, pancreatic, gastrointestinal, hepatic, cardiovascular, metabolic, endocrine, immunological, allergic disease, or other major disorders History of asthma, chronic obstructive pulmonary disease, or emphysema Clinically significant neurologic disorder History of stomach or intestinal surgery or resection History of malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DNL151<br>Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days) | Drug: DNL151<br>* oral dose(s)<br>|
| Placebo Comparator: Placebo<br>Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days) | Drug: Placebo<br>* oral dose(s)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs |  | Up to 42 days | 
| PK parameter: Maximum observed concentration (Cmax) of DNL151 in plasma |  | Up to 42 days | 
| PK parameter: Time to maximum observed concentration (Tmax) of DNL151 in plasma |  | Up to 42 days | 
| PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL151 in plasma (single dosing only) |  | Up to 42 days | 
| PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL151 in plasma |  | Up to 42 days | 
| PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL151 in plasma (multiple dosing only) |  | Up to 42 days | 
| PK parameter: Apparent terminal elimination half-life (t1/2) of DNL151 in plasma |  | Up to 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of DNL151 in cerebrospinal fluid (CSF) (following selected single and multiple doses) |  | Up to 13 days | 
| The pharmacodynamics of DNL151 in whole blood as measured by the percent change from baseline in pS935 |  | Up to 42 days |