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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: DNL201; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 05247
      • Clinical Site(s)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DNL201; Part 1: Single-ascending dose cohorts; Part 2: Multiple-ascending dose cohorts (10 days); Part 3: Additional multiple-dose cohort (10 days)	Drug: DNL201; Oral dose(s)
Placebo Comparator: Placebo; Part 1: Single-ascending dose cohorts; Part 2: Multiple-ascending dose cohorts (10 days); Part 3: Additional multiple-dose cohort (10 days)	Drug: Placebo; Oral dose(s)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Denali Therapeutics Inc.
• Investigators: Study Director: Danna Jennings, MD, Denali Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): August 8, 2018
• Study Completion (Actual): August 8, 2018

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: September 10, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 10, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: DNLI-B-0001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No