Clinical trial NCT04581772: A Study to Evaluate the Bioavailability and Safety of DNL343 in Healthy Volunteers
Official title: A Phase 1 Open-Label, Randomized, Crossover Study to Evaluate the Bioavailability, Effect of Food, Palatability, and Safety of Various DNL343 Oral Formulations in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-09
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 relative bioavailability study carried out in approximately 24 healthy male subjects and healthy female subjects of non childbearing potential to investigate the effects of formulation and food on the safety, tolerability, and pharmacokinetics (PK) of DNL343.


Eligibility criteria: Key Inclusion Criteria:

* Body mass index (BMI) ≥18.5 to \< 30 kg/m2 and body weight of at least 50 kg
* For women: Must have been surgically sterilized or be postmenopausal.

Key Exclusion Criteria:

* History of clinically significant endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders
* History of malignancy, except fully resected basal cell carcinoma
* History of clinically significant neurologic or psychiatric diseases; head trauma with loss of consciousness; or clinically significant depression or suicidal ideation

Primary outcomes:
measure: PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma
timeFrame: Up to 15 days
measure: PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma
timeFrame: Up to 15 days
measure: PK Parameter: Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of DNL343 in plasma
timeFrame: Up to 15 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 15 days
Secondary outcomes:
measure: PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma in the fed versus fasted states
timeFrame: Up to 15 days
measure: PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma in the fed versus fasted states
timeFrame: Up to 15 days
measure: PK Parameter: Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of DNL343 in plasma in the fed versus fasted states
timeFrame: Up to 15 days
measure: PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma in the fed versus fasted states
timeFrame: Up to 15 days
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 15 days
Other outcomes:
Locations:
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies Ltd.
state: Auckland
Study officials:
affiliation: Denali Therapeutics Inc.
name: Richard Tsai, MD
role: STUDY_DIRECTOR
References: