Clinical trial NCT04557800: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL151 in Healthy Volunteers
Official title: A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of DNL151 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-22
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.).

Eligibility 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs
timeFrame: Up to 42 days
measure: PK parameter: Maximum observed concentration (Cmax) of DNL151 in plasma
timeFrame: Up to 42 days
measure: PK parameter: Time to maximum observed concentration (Tmax) of DNL151 in plasma
timeFrame: Up to 42 days
measure: PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL151 in plasma (single dosing only)
timeFrame: Up to 42 days
measure: 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
timeFrame: Up to 42 days
measure: PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL151 in plasma (multiple dosing only)
timeFrame: Up to 42 days
measure: PK parameter: Apparent terminal elimination half-life (t1/2) of DNL151 in plasma
timeFrame: Up to 42 days
Secondary outcomes:
measure: Concentration of DNL151 in cerebrospinal fluid (CSF) (following selected single and multiple doses)
timeFrame: Up to 13 days
measure: The pharmacodynamics of DNL151 in whole blood as measured by the percent change from baseline in pS935
timeFrame: Up to 42 days
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
state: South Holland
city: Groningen
country: Netherlands
facility: PRA Health Sciences, Van Swietenlaan
Study officials:
affiliation: Denali Therapeutics Inc.
name: Andres Cruz-Herranz
role: STUDY_DIRECTOR
References: