Healthy Volunteers
Conditions
Brief summary
This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study conducted in three parts.
Interventions
DRUGDNL201
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 DNL201 in plasma | Up to 10 days |
| PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL201 in plasma | Up to 10 days |
| PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL201 in plasma (multiple dosing only) | Up to 10 days |
| PK parameter: Maximum observed concentration (Cmax) of DNL201 in plasma | Up to 10 days |
| Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs | Up to 20 days |
| PK parameter: Time to maximum observed concentration (Tmax) of DNL201 in plasma | Up to 10 days |
| PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL201 in plasma (single dosing only) | Up to 10 days |
Secondary
| Measure | Time frame |
|---|---|
| The pharmacodynamics of DNL201 in whole blood as measured by the percent change from baseline in pS935 | Up to 10 days |
| Concentration of DNL201 in cerebrospinal fluid (CSF) (following selected single and multiple doses) | Up to 10 days |
Countries
United States
Outcome results
None listed