Healthy Volunteers
Conditions
Brief summary
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
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.).
Interventions
DRUGDNL151
oral dose(s)
DRUGPlacebo
oral dose(s)
Sponsors
Denali Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK parameter: Apparent terminal elimination half-life (t1/2) of DNL151 in plasma | 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 |
| 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 |
Secondary
| Measure | 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 |
Countries
Netherlands
Outcome results
None listed