A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL201 in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: DNL201; Drug: Placebo

• Registration Number: NCT04551534
• Lead Sponsor: Denali Therapeutics Inc.

Brief Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study conducted in three parts.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-06-01
• Primary Completion: 2018-08-08
• Study Completion: 2018-08-08
• Status Verified: 2020-09
• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-09-10
• Last Update Submitted: 2020-09-10
• Study First Posted: 2020-09-16
• Last Update Posted: 2020-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 122

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
DNL201	DNL201	Part 1: Single-ascending dose cohorts; Part 2: Multiple-ascending dose cohorts (10 days); Part 3: Additional multiple-dose cohort (10 days)
Placebo	Placebo	Part 1: Single-ascending dose cohorts; Part 2: Multiple-ascending dose cohorts (10 days); Part 3: Additional multiple-dose cohort (10 days)

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), and discontinuations due to TEAEs	Up to 20 days
PK parameter: Maximum observed concentration (Cmax) of DNL201 in plasma	Up to 10 days
PK parameter: Time to maximum observed concentration (Tmax) of DNL201 in plasma	Up to 10 days
PK parameter: The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL201 in plasma (single dosing only)	Up to 10 days
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	Up to 10 days
PK parameter: The area under the concentration-time curve over a dosing interval (AUC0-τ) of DNL201 in plasma (multiple dosing only)	Up to 10 days
PK parameter: Apparent terminal elimination half-life (t1/2) of DNL201 in plasma	Up to 10 days

Secondary Outcome Measures

Name	Time	Method
Concentration of DNL201 in cerebrospinal fluid (CSF) (following selected single and multiple doses)	Up to 10 days
The pharmacodynamics of DNL201 in whole blood as measured by the percent change from baseline in pS935	Up to 10 days

Trial Locations

Locations (1)

Clinical Site(s); 🇺🇸 Dallas, Texas, United States