A Study to Evaluate the Bioavailability and Safety of DNL343 in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: DNL343
* Drug: Placebo
* Drug: DNL343


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br> | Drug: DNL343<br>* Multiple oral doses<br>Drug: Placebo<br>* Single oral dose<br>|
| Experimental: Cohort B<br> | Drug: DNL343<br>* Multiple oral doses<br>Drug: Placebo<br>* Single oral dose<br>|
| Experimental: Cohort C<br> | Drug: DNL343<br>* Single oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma |  | Up to 15 days | 
| PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma |  | Up to 15 days | 
| PK Parameter: Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of DNL343 in plasma |  | Up to 15 days | 
| PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma |  | Up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter: Maximum observed concentration (Cmax) of DNL343 in plasma in the fed versus fasted states |  | Up to 15 days | 
| PK parameter: Time to maximum observed concentration (Tmax) of DNL343 in plasma in the fed versus fasted states |  | Up to 15 days | 
| 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 |  | Up to 15 days | 
| 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 |  | Up to 15 days | 
| Incidence of treatment-emergent adverse events (TEAEs) |  | Up to 15 days |