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.
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.).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
96
Centre for Human Drug Research (CHDR)
Leiden, South Holland, Netherlands
Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs
Time frame: Up to 20 days
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma
Time frame: 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
Time frame: Up to 20 days
PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma
Time frame: 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
Time frame: Up to 20 days
PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma
Time frame: Up to 20 days
PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma
Time frame: Up to 20 days
PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)
Time frame: Up to 20 days
PK parameter: Estimation of renal clearance (CLR)
Time frame: Up to 20 days
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PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)
Time frame: 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)
Time frame: 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)
Time frame: Up to 20 days