Clinical trial NCT04268784: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 in Healthy Volunteers
Official title: A Phase 1, Single-Center, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL343 In Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-02-13
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.).

Eligibility 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

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs
timeFrame: Up to 20 days
measure: PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma
timeFrame: Up to 20 days
measure: 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
timeFrame: Up to 20 days
measure: PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma
timeFrame: Up to 20 days
measure: 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
timeFrame: Up to 20 days
measure: PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma
timeFrame: Up to 20 days
measure: PK parameter: Apparent terminal elimination rate constant (λz) with the respective t½ of DNL343 in plasma
timeFrame: Up to 20 days
Secondary outcomes:
measure: PK parameter: The amount of DNL343 excreted in urine from time zero to 48 hours postdose (Ae48)
timeFrame: Up to 20 days
measure: PK parameter: Estimation of renal clearance (CLR)
timeFrame: Up to 20 days
measure: PK parameter: Concentration of DNL343 in cerebrospinal fluid (CSF)
timeFrame: Up to 20 days
measure: 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)
timeFrame: Up to 20 days
measure: The PD of DNL343 in blood as measured by percent reduction in ISR gene expression levels measured by quantitative polymerase chain reaction (qPCR)
timeFrame: Up to 20 days
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research (CHDR)
state: South Holland
Study officials:
affiliation: Denali Therapeutics Inc.
name: Richard Tsai, MD
role: STUDY_DIRECTOR
References: