Healthy Volunteers
Conditions
Brief summary
This is a Phase 1 study carried out at a single site in 88 healthy male subjects and healthy female subjects of non childbearing potential to investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of DNL343.
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
DRUGDNL343
Single and repeating oral dose(s)
DRUGPlacebo
Single and repeating 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 50 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Women of non-childbearing potential and men; aged 18-50 years, inclusive * BMI 18-32 kg/m², inclusive, and body weight of at least 50 kg Key
Exclusion criteria
* History of clinically significant neurologic, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma | Up to 20 days |
| PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma | Up to 20 days |
| PK parameter: Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC[0-last]) of DNL343 in plasma | Up to 20 days |
| PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma | Up to 20 days |
| PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma | Up to 20 days |
| Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs | Up to 20 days |
| PK parameter: The area under the concentration-time curve from zero to 12 or 24 hours for twice daily (BID) or once daily (QD) dosing, respectively (AUC0-τ) of DNL343 in plasma | Up to 20 days |
Secondary
| Measure | Time frame |
|---|---|
| PK parameter: Estimation of renal clearance (CLR) | Up to 20 days |
| PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF) | Up to 20 days |
| The PD of DNL343 in blood as measured by percent reduction of integrated stress response (ISR) protein levels measured by enzyme-linked immunosorbent assay (ELISA) | Up to 20 days |
| The PD of DNL343 in blood as measured by percent reduction in ISR gene expression levels measured by quantitative polymerase chain reaction (qPCR) | Up to 20 days |
| PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48) | Up to 20 days |
Countries
Netherlands
Outcome results
None listed