Clinical trial NCT04551534: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL201 in Healthy Volunteers
Official title: A First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of DNL201 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 122
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- and multiple-ascending oral dose study conducted in three parts.


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 20 days
measure: PK parameter: Maximum observed concentration (Cmax) of DNL201 in plasma
timeFrame: Up to 10 days
measure: PK parameter: Time to maximum observed concentration (Tmax) of DNL201 in plasma
timeFrame: Up to 10 days
measure: PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL201 in plasma (single dosing only)
timeFrame: Up to 10 days
measure: 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
timeFrame: Up to 10 days
measure: PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL201 in plasma (multiple dosing only)
timeFrame: Up to 10 days
measure: PK parameter: Apparent terminal elimination half-life (t1/2) of DNL201 in plasma
timeFrame: Up to 10 days
Secondary outcomes:
measure: Concentration of DNL201 in cerebrospinal fluid (CSF) (following selected single and multiple doses)
timeFrame: Up to 10 days
measure: The pharmacodynamics of DNL201 in whole blood as measured by the percent change from baseline in pS935
timeFrame: Up to 10 days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Clinical Site(s)
state: Texas
Study officials:
affiliation: Denali Therapeutics Inc.
name: Danna Jennings, MD
role: STUDY_DIRECTOR
References: