A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Of DNL151 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- DNL151
- Conditions
- Healthy Volunteers
- Sponsor
- Denali Therapeutics Inc.
- Enrollment
- 186
- Locations
- 2
- Primary Endpoint
- Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.).
Investigators
Eligibility Criteria
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
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
Arms & Interventions
DNL151
Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days)
Intervention: DNL151
Placebo
Part A: Single-ascending dose cohorts; Part B: Multiple-ascending dose cohorts (10 days); Part C: Single-dose cohort; Part D: Additional multiple-dose cohort (28 days); Part E Multiple-ascending dose cohorts (14 days)
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs
Time Frame: Up to 42 days
PK parameter: Maximum observed concentration (Cmax) of DNL151 in plasma
Time Frame: Up to 42 days
PK parameter: Time to maximum observed concentration (Tmax) of DNL151 in plasma
Time Frame: Up to 42 days
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL151 in plasma (single dosing only)
Time Frame: Up to 42 days
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
Time Frame: Up to 42 days
PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL151 in plasma (multiple dosing only)
Time Frame: Up to 42 days
PK parameter: Apparent terminal elimination half-life (t1/2) of DNL151 in plasma
Time Frame: Up to 42 days
Secondary Outcomes
- Concentration of DNL151 in cerebrospinal fluid (CSF) (following selected single and multiple doses)(Up to 13 days)
- The pharmacodynamics of DNL151 in whole blood as measured by the percent change from baseline in pS935(Up to 42 days)