A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-DNL343 Following a Single Oral Dose in Healthy Male Participants

A Study of the Pharmacokinetics of [14C]-DNL343 Following a Single Oral Dose in Healthy Male Participants

This is a Phase 1, open-label, nonrandomized, single-dose study in healthy male participants to investigate the absorption, metabolism and excretion of DNL343.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [14C]-DNL343

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males, aged between 18 to 65 years, inclusive
• Body mass index between 18.0 and 32.0 kg/m2
• In good health
• When engaging in sex with a woman of child bearing potential, both the male participant and his female partner must use highly effective contraception
• History of a minimum of 1 bowel movement per day

Exclusion Criteria:

• History or clinical manifestation of any clinically significant metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder
• Have a history of malignancy, except fully resected basal cell carcinoma
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs
• Have previously completed or withdrawn from this study or any other study investigating DNL343 and have previously received DNL343

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 14C-DNL343	Drug: [14C]-DNL343; Single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameter: AUC0-∞	The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of DNL343 in plasma	28 days
PK Parameter: AUC0-tlast	Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-tlast) of DNL343 in plasma	28 days
PK Parameter: Cmax	Maximum observed concentration (Cmax) of DNL343 in plasma	28 days
PK Parameter: Tmax	Time to maximum observed concentration (Tmax) of DNL343 in plasma	28 days
PK Parameter: t1/2	Terminal elimination half-life (t1/2) of DNL343 in plasma	28 days
Total radioactivity in blood-to-plasma ratio		28 days
Extent and rate of recovery of total radioactivity in urine and feces		28 days
Total radioactivity in plasma and whole blood		28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameter: AUC0-∞	The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of a DNL343 metabolite in plasma	28 days
PK Parameter: AUC0-tlast	Area under the concentration-time curve from time zero to the last quantifiable time point (AUC0-tlast) of a DNL343 metabolite in plasma	28 days
PK Parameter: Cmax	Maximum observed concentration (Cmax) of a DNL343 metabolite in plasma	28 days
PK Parameter: Tmax	Time to maximum observed concentration (Tmax) of a DNL343 metabolite in plasma	28 days
PK Parameter: t1/2	Terminal elimination half-life (t1/2) of a DNL343 metabolite in plasma	28 days
DNL343 and a DNL343 metabolite recoveries in urine		28 days
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs)		28 days

Collaborators and Investigators

• Sponsor: Denali Therapeutics Inc.
• Investigators: Study Director: Ana-Claire Meyer, MD, Denali Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: DNLI-F-0009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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